Research activity information

• Oct. 2024 神戸大学, 学長表彰


• May 2024 CINP (International College of Neuropsychopharmacology), CINP Sumitomo Pharma Brain Health Basic Research Award

  Tomoyuki Furuyashiki


• Oct. 2023 神戸大学, 学長表彰


• Oct. 2022 神戸大学, 学長表彰


• Oct. 2021 神戸大学, 学長表彰


• Oct. 2020 神戸大学, 学長表彰


• Oct. 2019 神戸大学, 学長表彰

  古屋敷 智之


• Oct. 2018 Kobe University, President's award

  Tomoyuki Furuyashiki


• Nov. 2015 Astellas Foundation for Research on Metabolic Disorders, Best President’s Award

  Tomoyuki Furuyashiki


• Mar. 2012 The Japanese Pharmacological Society, 27th Young Investigator Award

  Tomoyuki Furuyashiki

• Alteration of COX-1 and TLR4 expression in the mouse brain during chronic social defeat stress revealed by Positron Emission Tomography study.

  Yumika Motooka, Ryota Shinohara, Shiho Kitaoka, Ai Uryu, Dongrui Li, Hiroyuki Neyama, Yilong Cui, Tatsuya Kida, Wakiko Arakaki, Hisashi Doi, Yasuyoshi Watanabe, Tomoyuki Furuyashiki

  Despite the recognized roles of neuroinflammation in mental illnesses, PET imaging on currently available biomarkers has limitations due to the lack of evidence demonstrating their relationship to the molecular and cellular events of inflammation associated with the pathology of mental illness. Rodent stress models, such as chronic social defeat stress (SDS), have identified crucial roles for COX-1 and TLR4, which are innate immune molecules, in chronic SDS-induced neuroinflammation and its behavioral consequences. In this study, we performed COX-1 and TLR4 PET imaging at multiple time points during chronic SDS in mice. For COX-1 PET imaging, we used the COX-1 PET probe (S)-[18F]KTP-Me. Subchronic SDS transiently increased uptake and slower washout in broad regions of the brain, including the cerebral cortex, hippocampus, striatum, and thalamus. For TLR4 PET imaging, we developed a new BBB-permeable PET probe, [11C]1, which detected LPS-induced neuroinflammation. Washout of [11C]1 was facilitated in the cerebellum after subchronic and chronic SDS and in the pons-medulla after chronic SDS. Collectively, our findings suggest the potential usefulness of COX-1 and TLR4 PET imaging in visualizing and understanding time-dependent process of neuroinflammation in stress-related mental illnesses.

  Mar. 2025, Journal of pharmacological sciences, 157(3) (3), 156 - 166, English, Domestic magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• C57BL/6J and C57BL/6N mice show distinct aging-associated behavioral alterations

  Rui Yamada, Hirotaka Nagai, Io Horikawa, Wenran Qiu, Yunhui Zhu, Kohei Ota, Tomoyuki Furuyashiki

  Feb. 2025, Journal of Pharmacological Sciences

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• The activation of the piriform cortex to lateral septum pathway during chronic social defeat stress is crucial for the induction of behavioral disturbance in mice

  Yuki Okuda, Dongrui Li, Yuzuki Maruyama, Hirokazu Sonobe, Tomoyuki Mano, Kazuki Tainaka, Ryota Shinohara, Tomoyuki Furuyashiki

  Chronic stress induces neural dysfunctions and risks mental illnesses. Clinical and preclinical studies have established the roles of brain regions underlying emotional and cognitive functions in stress and depression. However, neural pathways to perceive sensory stimuli as stress to cause behavioral disturbance remain unknown. Using whole-brain imaging of Arc-dVenus neuronal response reporter mice and machine learning analysis, here we unbiasedly demonstrated different patterns of contribution of widely distributed brain regions to neural responses to acute and chronic social defeat stress (SDS). Among these brain regions, multiple sensory cortices, especially the piriform (olfactory) cortex, primarily contributed to classifying neural responses to chronic SDS. Indeed, SDS-induced activation of the piriform cortex was augmented with repetition of SDS, accompanied by impaired odor discrimination. Axonal tracing and chemogenetic manipulation showed that excitatory neurons in the piriform cortex directly project to the lateral septum and activate it in response to chronic SDS, thereby inducing behavioral disturbance. These results pave the way for identifying a spatially defined sequence of neural consequences of stress and the roles of sensory pathways in perceiving chronic stress in mental illness pathology.

  Dec. 2024, Neuropsychopharmacology, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Left atrial single-cell transcriptomics reveals amphiregulin as a surrogate marker for atrial fibrillation.

  Yuya Suzuki, Takuo Emoto, Shunsuke Sato, Takeshi Yoshida, Mitsuhiko Shoda, Hiromi Endoh, Manabu Nagao, Tomoyo Hamana, Taishi Inoue, Tomohiro Hayashi, Eriko Nitta, Hiroki Konishi, Kunihiko Kiuchi, Mitsuru Takami, Kimitake Imamura, Masayuki Taniguchi, Masatoshi Inoue, Toshihiro Nakamura, Yusuke Sonoda, Hiroyuki Takahara, Kazutaka Nakasone, Kyoko Yamamoto, Kenichi Tani, Hidehiro Iwai, Yusuke Nakanishi, Shogo Yonehara, Atsushi Murakami, Ryuji Toh, Takenao Ohkawa, Tomoyuki Furuyashiki, Ryo Nitta, Tomoya Yamashita, Ken-Ichi Hirata, Koji Fukuzawa

  Atrial fibrillation (AF) is strongly associated with strokes, heart failure, and increased mortality. This study aims to identify the monocyte-macrophage heterogeneity and interactions of these cells with non-immune cells, and to identify functional biomarkers in patients with AF. Therefore, we assess the single cell landscape of left atria (LA), using a combination of single cell and nucleus RNA-seq. Myeloid cells in LA tissue are categorized into five macrophage clusters, three monocyte clusters, and others. Cell-Chat analysis revealed that monocytes and IL1B+ macrophages send epidermal growth factor (EGF) signals to fibroblasts. Amphiregulin (AREG) is the most upregulated gene in monocytes and IL1B+ macrophages in the AF group, compared with healthy controls from other groups. Serum AREG levels are higher in patients with persistent AF. These data suggested that EGF signaling pathway could be a therapeutic target for AF and serum AREG levels provide an effective biomarker for predicting persistent AF.

  Dec. 2024, Communications biology, 7(1) (1), 1601 - 1601, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Editorial: Neuroscience of resilience for mental health.

  Tomoyuki Furuyashiki, Scott J Russo

  Nov. 2024, Neuroscience research, English, International magazine


• Supplementation with whey peptide rich in β-lactolin improves trait anxiety and subjective stress in healthy adults: a randomized, double-blind, placebo-controlled study.

  Tatsuhiro Ayabe, Masakazu Shinohara, Masahiro Kita, Chika Takahashi, Jiro Saito, Tomoyuki Furuyashiki, Kenji Toba, Satoshi Umeda, Yasuhisa Ano

  Mental disorders have become one of the most burdensome health concerns. We have previously demonstrated that whey-derived β-lactolin (glycine-thereonine-tryptophan-tyrosine tetrapeptide) activates dopaminergic systems and improves psychiatric function in rodents. However, the effects of β-lactolin on human mood states have not been investigated. This randomized, double-blind, placebo-controlled study aimed to evaluate the effects of supplementation with β-lactolin-rich whey peptide on human mood states. Sixty healthy adults (aged 45-64 years) with relatively low psychological health were randomly allocated to receive either whey peptide (containing β-lactolin 1.6 mg/day) or placebo for 6 weeks. Mood states (primary outcomes) were evaluated using self-reporting questionnaires. Health-related quality of life (QOL), salivary stress marker and lipid mediator levels were evaluated as secondary outcomes. Compared with placebo, supplementation with β-lactolin improved changes in trait anxiety (p = 0.046), as assessed using the state-trait anxiety inventory, and in subjective stress (p = 0.043), as assessed using the Perceived Stress Scale. In the assessment of QOL, changes in the vitality subscale and mental health summary score of the 36-Item Short-Form Health Survey were improved in the β-lactolin group. The levels of salivary immunoglobulin A were significantly higher in the β-lactolin group. In a subgroup analysis by median age (54.5 years), subjective stress and salivary prostaglandin levels were significantly decreased by β-lactolin supplementation in the 45-54 -year-old subgroup. In conclusion, supplementation with β-lactolin improves trait anxiety, subjective stress, and psychological QOL, which may be associated with immunologic responses detected via salivary analysis.

  Oct. 2024, Scientific reports, 14(1) (1), 23444 - 23444, English, International magazine

  Scientific journal


• Intense impact of IL-1β expressing inflammatory macrophages in acute aortic dissection.

  Taishi Inoue, Takuo Emoto, Katsuhiro Yamanaka, Shunya Chomei, Shunsuke Miyahara, Hiroaki Takahashi, Ryohei Shinohara, Takeshi Kondo, Masayuki Taniguchi, Tomoyuki Furuyashiki, Tomoya Yamashita, Ken-Ichi Hirata, Kenji Okada

  There is no treatment for acute aortic dissection (AAD) targeting inflammatory cells. We aimed to identify the new therapeutic targets associated with inflammatory cells. We characterized the specific distribution of myeloid cells of both human type A AAD samples and a murine AAD model generated using angiotensin II (ANGII) and β-aminopropionitrile (BAPN) by single-cell RNA sequencing (scRNA-seq). We also examined the effect of an anti-interleukin-1β (IL-1β) antibody in the murine AAD model. IL1B+ inflammatory macrophages and classical monocytes were increased in human AAD samples. Trajectory analysis demonstrated that IL1B+ inflammatory macrophages differentiated from S100A8/9/12+ classical monocytes uniquely observed in the aorta of AAD. We found increased infiltration of neutrophils and monocytes with the expression of inflammatory cytokines in the aorta and accumulation of inflammatory macrophages before the onset of macroscopic AAD in the murine AAD model. In blocking experiments using an anti-IL-1β antibody, it improved survival of murine AAD model by preventing elastin degradation. We observed the accumulation of inflammatory macrophages expressing IL-1β in both human AAD samples and in a murine AAD model. Anti-IL-1β antibody could improve the mortality rate in mice, suggesting that it may be a treatment option for AAD.

  Jun. 2024, Scientific reports, 14(1) (1), 14893 - 14893, English, International magazine

  Scientific journal


• Single-Cell RNA Sequencing Reveals an Immune Landscape of CD4+ T Cells in Coronary Culprit Plaques With Acute Coronary Syndrome in Humans-Brief Report.

  Shintaro Takeda, Takuo Emoto, Tomoya Yamashita, Hiroyuki Yamamoto, Tomofumi Takaya, Takahiro Sawada, Takeshi Yoshida, Masatoshi Inoue, Yuya Suzuki, Tomoyo Hamana, Taishi Inoue, Masayuki Taniguchi, Naoto Sasaki, Hiromasa Otake, Takenao Ohkawa, Tomoyuki Furuyashiki, Hiroya Kawai, Ken-Ichi Hirata

  BACKGROUND: Acute coronary syndrome (ACS) involves plaque-related thrombosis, causing primary ischemic cardiomyopathy or lethal arrhythmia. We previously demonstrated a unique immune landscape of myeloid cells in the culprit plaques causing ACS by using single-cell RNA sequencing. Here, we aimed to characterize T cells in a single-cell level, assess clonal expansion of T cells, and find a therapeutic target to prevent ACS. METHODS: We obtained the culprit lesion plaques from 4 patients with chronic coronary syndrome (chronic coronary syndrome plaques) and the culprit lesion plaques from 3 patients with ACS (ACS plaques) who were candidates for percutaneous coronary intervention with directional coronary atherectomy. Live CD45+ immune cells were sorted from each pooled plaque samples and applied to the 10× platform for single-cell RNA sequencing analysis. We also extracted RNA from other 3 ACS plaque samples and conducted unbiased TCR (T-cell receptor) repertoire analysis. RESULTS: CD4+ T cells were divided into 5 distinct clusters: effector, naive, cytotoxic, CCR7+ (C-C chemokine receptor type 7) central memory, and FOXP3 (forkhead box P3)+ regulatory CD4+ T cells. The proportion of central memory CD4+ T cells was higher in the ACS plaques. Correspondingly, dendritic cells also tended to express more HLAs (human leukocyte antigens) and costimulatory molecules in the ACS plaques. The velocity analysis suggested the differentiation flow from central memory CD4+ T cells into effector CD4+ T cells and that from naive CD4+ T cells into central memory CD4+ T cells in the ACS plaques, which were not observed in the chronic coronary syndrome plaques. The bulk repertoire analysis revealed clonal expansion of TCRs in each patient with ACS and suggested that several peptides in the ACS plaques work as antigens and induced clonal expansion of CD4+ T cells. CONCLUSIONS: For the first time, we revealed single cell-level characteristics of CD4+ T cells in patients with ACS. CD4+ T cells could be therapeutic targets of ACS. REGISTRATION: URL: https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000046521; Unique identifier: UMIN000040747.

  May 2024, Arteriosclerosis, thrombosis, and vascular biology, 44(5) (5), 1135 - 1143, English, International magazine

  Scientific journal


• Chronic stress alters lipid mediator profiles associated with immune-related gene expressions and cell compositions in mouse bone marrow and spleen.

  Io Horikawa, Hirotaka Nagai, Masayuki Taniguchi, Guowei Chen, Masakazu Shinohara, Tomohide Suzuki, Shinichi Ishii, Yoshio Katayama, Shiho Kitaoka, Tomoyuki Furuyashiki

  Despite the importance of lipid mediators in stress and depression and their link to inflammation, the influence of stress on these mediators and their role in inflammation is not fully understood. This study used RNA-seq, LC-MS/MS, and flow cytometry analyses in a mouse model subjected to chronic social defeat stress to explore the effects of acute and chronic stress on lipid mediators, gene expression, and cell population in the bone marrow and spleen. In the bone marrow, chronic stress induced a sustained transition from lymphoid to myeloid cells, accompanied by corresponding changes in gene expression. This change was associated with decreased levels of 15-deoxy-d12,14-prostaglandin J2, a lipid mediator that inhibits inflammation. In the spleen, chronic stress also induced a lymphoid-to-myeloid transition, albeit transiently, alongside gene expression changes indicative of extramedullary hematopoiesis. These changes were linked to lower levels of 12-HEPE and resolvins, both critical for inhibiting and resolving inflammation. Our findings highlight the significant role of anti-inflammatory and pro-resolving lipid mediators in the immune responses induced by chronic stress in the bone marrow and spleen. This study paves the way for understanding how these lipid mediators contribute to the immune mechanisms of stress and depression.

  Apr. 2024, Journal of pharmacological sciences, 154(4) (4), 279 - 293, English, Domestic magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Stress-induced stenotic vascular remodeling via reduction of plasma omega-3 fatty acid metabolite 4-oxoDHA by noradrenaline.

  Makoto Nishimori, Naomi Hayasaka, Kazunori Otsui, Nobutaka Inoue, Junko Asakura, Manabu Nagao, Ryuji Toh, Tatsuro Ishida, Ken-Ichi Hirata, Tomoyuki Furuyashiki, Masakazu Shinohara

  Stress has garnered significant attention as a prominent risk factor for inflammation-related diseases, particularly cardiovascular diseases (CVDs). However, the precise mechanisms underlying stress-driven CVDs remain elusive, thereby impeding the development of preventive and therapeutic strategies. To explore the correlation between plasma lipid metabolites and human depressive states, liquid chromatography-mass spectrometry (LC/MS) based analysis of plasma and the self-rating depression (SDS) scale questionnaire were employed. We also used a mouse model with restraint stress to study its effects on plasma lipid metabolites and stenotic vascular remodeling following carotid ligation. In vitro functional and mechanistic studies were performed using macrophages, endothelial cells, and neutrophil cells. We revealed a significant association between depressive state and reduced plasma levels of 4-oxoDHA, a specific omega-3 fatty acid metabolite biosynthesized by 5-lipoxygenase (LO), mainly in neutrophils. In mice, restraint stress decreased plasma 4-oxoDHA levels and exacerbated stenotic vascular remodeling, ameliorated by 4-oxoDHA supplementation. 4-oxoDHA enhanced Nrf2-HO-1 pathways, exerting anti-inflammatory effects on endothelial cells and macrophages. One of the stress hormones, noradrenaline, reduced 4-oxoDHA and the degraded 5-LO in neutrophils through the proteasome system, facilitated by dopamine D2-like receptor activation. Our study proposed circulating 4-oxoDHA levels as a stress biomarker and supplementation of 4-oxoDHA as a novel therapeutic approach for controlling stress-related vascular inflammation.

  Feb. 2024, Scientific reports, 14(1) (1), 4178 - 4178, English, International magazine

  Scientific journal


• Author Correction: Accelerated preprocessing of large numbers of brain images by parallel computing on supercomputers.

  Takehiro Jimbo, Hidetoshi Matsuo, Yuya Imoto, Takumi Sodemura, Makoto Nishimori, Yoshinari Fukui, Takuya Hayashi, Tomoyuki Furuyashiki, Ryoichi Yokoyama

  "Preprocessing" is the first step required in brain image analysis that improves the overall quality and reliability of the results. However, it is computationally demanding and time-consuming, particularly to handle and parcellate complicatedly folded cortical ribbons of the human brain. In this study, we aimed to shorten the analysis time for data preprocessing of 1410 brain images simultaneously on one of the world's highest-performing supercomputers, "Fugaku." The FreeSurfer was used as a benchmark preprocessing software for cortical surface reconstruction. All the brain images were processed simultaneously and successfully analyzed in a calculation time of 17.33 h. This result indicates that using a supercomputer for brain image preprocessing allows big data analysis to be completed shortly and flexibly, thus suggesting the possibility of supercomputers being used for expanding large data analysis and parameter optimization of preprocessing in the future.

  Jan. 2024, Scientific reports, 14(1) (1), 2233 - 2233, English, International magazine

  Scientific journal


• Overexpression of NT-3 in the hippocampus suppresses the early phase of the adult neurogenic process

  Nanami Kasakura, Yuka Murata, Asuka Shindo, Shiho Kitaoka, Tomoyuki Furuyashiki, Kanzo Suzuki, Eri Segi-Nishida

  The dentate gyrus (DG) of the hippocampus regulates stress-related emotional behaviors and ensures neurogenesis throughout life. Neurotrophin-3 (NT-3) is a neurotrophic factor that regulates neuronal differentiation, survival, and synaptic formation in both the peripheral and central nervous systems. NT-3 is expressed in the adult DG of the hippocampus; several chronic stress conditions enhance NT-3 expression in rodents. However, functional modulation of the adult DG by NT-3 signaling remains unclear. To directly investigate the impact of NT-3 on DG function, NT-3 was overexpressed in the hippocampal ventral DG by an adeno-associated virus carrying NT-3 (AAV-NT-3). Four weeks following the AAV-NT-3 injection, high NT-3 expression was observed in the ventral DG. We examined the influence of NT-3 overexpression on the neuronal responses and neurogenic processes in the ventral DG. NT-3 overexpression significantly increased the expression of the mature DG neuronal marker calbindin and immediate early genes, such as Fos and Fosb, thereby suggesting DG neuronal activation. During neurogenesis, the number of proliferating cells and immature neurons in the subgranular zone of the DG significantly decreased in the AAV-NT-3 group. Among the neurogenesis-related factors, Vegfd, Lgr6, Bmp7, and Drd1 expression significantly decreased. These results demonstrated that high NT-3 levels in the hippocampus regulate the activation of mature DG neurons and suppress the early phase of neurogenic processes, suggesting a possible role of NT-3 in the regulation of adult hippocampal function under stress conditions.

  Frontiers Media SA, Jul. 2023, Frontiers in Neuroscience, 17, 1178555 - 1178555, English, International magazine

  Scientific journal


• Stress-induced vascular remodeling: novel insight into the role of omega-3 fatty acid metabolite, 4-oxoDHA

  Makoto Nishimori, Naomi Hayasaka, Kazunori Otsui, Nobutaka Inoue, Manabu Nagao, Ryuji Toh, Tatsuro Ishida, Ken-ichi Hirata, Tomoyuki Furuyashiki, Masakazu Shinohara

  Jul. 2023


• Repeated Social Defeat Stress Induces HMGB1 Nuclear Export in Prefrontal Neurons, Leading to Social Avoidance in Mice

  Shiho Kitaoka, Ayaka Tomohiro, Shinya Ukeshima, Keyue Liu, Hidenori Wake, Shinya H. Kimura, Yasuhiko Yamamoto, Masahiro Nishibori, Tomoyuki Furuyashiki

  Inflammation has been associated with depression, and innate immune receptors, such as the Toll-like receptor (TLR) 2/4 in the medial prefrontal cortex (mPFC), are crucial for chronic stress-induced depression-related behaviors in mice. HMGB1, a putative ligand for TLR2/4, has been suggested to promote depression-related behaviors under acute stress. However, the roles of endogenous HMGB1 under chronic stress remain to be investigated. Here, we found that the cerebroventricular infusion of HMGB1 proteins blocked stress-induced social avoidance and that HMGB1-neutralizing antibodies augmented repeated social defeat stress-induced social avoidance in mice, suggesting the antidepressive-like effect of HMGB1 in the brain. By contrast, the infusion of HMGB1-neutralizing antibodies to the mPFC and HMGB1 knockout in α-CaMKII-positive forebrain neurons attenuated the social avoidance, suggesting the pro-depressive-like effect of HMGB1 released from prefrontal neurons under chronic stress. In addition, repeated social defeat stress induced HMGB1 nuclear export selectively in mPFC neurons, which was abolished in the mice lacking RAGE, one of HMGB1 receptors, suggesting the positive feedback loop of HMGB1-RAGE signaling under chronic stress. These findings pave the way for identifying multiple roles of HMGB1 in the brain for chronic stress and depression.

  MDPI AG, Jul. 2023, Cells, 12(13) (13), 1789 - 1789, English, International magazine

  Scientific journal


• High salt induces cognitive impairment via the interaction of angiotensin II-AT1 and prostaglandin E2-EP1 systems.

  Hisayoshi Kubota, Kazuo Kunisawa, Bolati Wulaer, Masaya Hasegawa, Hitomi Kurahashi, Takatoshi Sakata, Hiroyuki Tezuka, Masanori Kugita, Shizuko Nagao, Taku Nagai, Tomoyuki Furuyashiki, Shuh Narumiya, Kuniaki Saito, Toshitaka Nabeshima, Akihiro Mouri

  BACKGROUND AND PURPOSE: High salt (HS) intake has been associated with hypertension and cognitive impairment. It is well-known that angiotensin II (Ang II)-AT1 and prostaglandin E2 (PGE2)-EP1 systems are involved in hypertension and neurotoxicity. However, the involvement of these systems in HS-mediated hypertension and emotional and cognitive impairments remains unclear. EXPERIMENTAL APPROACH: Mice were loaded with HS solution (2% NaCl drinking water) for 12 weeks and blood pressure was monitored. Subsequently, effects of HS intake on emotional and cognitive function and tau phosphorylation in the prefrontal cortex (PFC) and hippocampus (HIP) were investigated. The involvement of Ang II-AT1 and PGE2-EP1 systems in HS-induced hypertension and neuronal and behavioral impairments was examined by treatment with losartan, an AT1 receptor blocker (ARB), or EP1 gene knockout. KEY RESULTS: We demonstrated that hypertension and impaired social behavior and object recognition memory following HS intake could be associated with tau hyperphosphorylation, decreased phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII), and postsynaptic density protein 95 (PSD95) expression in the PFC and HIP of mice. These changes were blocked by pharmacological treatment with losartan or EP1 gene knockout. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that the interaction of Ang II-AT1 and PGE2-EP1 systems could be novel therapeutic targets for hypertension-induced cognitive impairment.

  Apr. 2023, British journal of pharmacology, 180(18) (18), 2393 - 2411, English, International magazine

  Scientific journal


• 脳内炎症は骨格筋のC/EBP経路を介してストレス性筋萎縮を促進する

  内山 奏, 平田 悠, 野村 和弘, Wijaya Hendy, 谷口 将之, 北岡 志保, 古屋敷 智之, 小川 渉

  日本臨床分子医学会, Apr. 2023, 日本臨床分子医学会学術総会プログラム・抄録集, 58回, 56 - 56, Japanese


• Microglial subpopulations with distinct transcriptome signatures vary across brain regions in the resting mouse brain.

  Rei Mishima, Masayuki Taniguchi, Kazutoshi Matsushita, Bowen Tian, Tomoyuki Furuyashiki

  Microglia are crucial for tissue homeostasis and its disturbance. However, microglial heterogeneity and its relationship with microglial activation in physiological conditions remain elusive. Using single-cell RNA sequencing, we identified microglial subpopulations with distinct transcriptome signatures in the resting brain. The distribution of two major, continuous subpopulations varied across brain regions, especially between cerebral cortices and the hypothalamus. Lipopolysaccharide and chronic social defeat stress, both of which involve the innate immune receptor TLR4, upregulate the marker genes of selective microglial subpopulations. These findings suggest that microglial subpopulations contribute to the heterogeneity of microglial transcriptome and responsiveness within and across brain regions.

  Mar. 2023, Journal of pharmacological sciences, 151(3) (3), 142 - 147, English, Domestic magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• N-Acetylcysteine Suppresses Microglial Inflammation and Induces Mortality Dose-Dependently via Tumor Necrosis Factor-α Signaling.

  Mai Sakai, Zhiqian Yu, Masayuki Taniguchi, Rosanne Picotin, Nanami Oyama, David Stellwagen, Chiaki Ono, Yoshie Kikuchi, Ko Matsui, Miharu Nakanishi, Hatsumi Yoshii, Tomoyuki Furuyashiki, Takaaki Abe, Hiroaki Tomita

  N-acetylcysteine (NAC) is an antioxidant that prevents tumor necrosis factor (TNF)-α-induced cell death, but it also acts as a pro-oxidant, promoting reactive oxygen species independent apoptosis. Although there is plausible preclinical evidence for the use of NAC in the treatment of psychiatric disorders, deleterious side effects are still of concern. Microglia, key innate immune cells in the brain, play an important role in inflammation in psychiatric disorders. This study aimed to investigate the beneficial and deleterious effects of NAC on microglia and stress-induced behavior abnormalities in mice, and its association with microglial TNF-α and nitric oxide (NO) production. The microglial cell line MG6 was stimulated by Escherichia coli lipopolysaccharide (LPS) using NAC at varying concentrations for 24 h. NAC inhibited LPS-induced TNF-α and NO synthesis, whereas high concentrations (≥30 mM) caused MG6 mortality. Intraperitoneal injections of NAC did not ameliorate stress-induced behavioral abnormalities in mice, but high-doses induced microglial mortality. Furthermore, NAC-induced mortality was alleviated in microglial TNF-α-deficient mice and human primary M2 microglia. Our findings provide ample evidence for the use of NAC as a modulating agent of inflammation in the brain. The risk of side effects from NAC on TNF-α remains unclear and merits further mechanistic investigations.

  Feb. 2023, International journal of molecular sciences, 24(4) (4), English, International magazine

  Scientific journal


• Microarray dataset of gene transcription in mouse microglia and peripheral monocytes in contextual fear conditioning.

  Zhiqian Yu, Mai Sakai, Hotaka Fukushima, Chiaki Ono, Yoshie Kikuchi, Ryuta Koyama, Ko Matsui, Tomoyuki Furuyashiki, Satoshi Kida, Hiroaki Tomita

  The transcription profile of microglia related to fear conditioning remains unclear. Here, we used Illumina MouseWG-6v2 microarrays to investigate the gene transcription changes in microglia and peripheral monocytes after contextual fear conditioning of C57BL/6 J mice. Mice were trained with or without a single minimized footshock stimulation (0-s or 2-s, 0.4 mA) and re-exposed to the training context without footshock for three different durations 24 h later: 0 min (FS0), 3 min (FS3), or 30 min (FS30). Whole brain microglia and peripheral monocytes were prepared 24 h after re-exposure using a neural tissue dissociation kit, including non-footshock controls for two re-exposure durations (Con3 and Con30). The data can be valuable for researchers interested in glial cells and neurotransmission studies and are related to the research article "Contextual fear conditioning regulates synapse-related gene transcription in mouse microglia".

  Feb. 2023, Data in brief, 46, 108862 - 108862, English, International magazine

  Scientific journal


• Neutrophil mobilization is crucial for chronic social stress-induced behavioral alterations in mice

  Toshihiro Hisasue, Qing Zhu, Yuka Ishikawa, Taro Kato, Shinichi Ishii, Yoshio Katayama, Yuta Yamaguchi, Ryota Shinohara, Tomoyuki Furuyashiki

  Japanese Pharmacological Society, 2023, Proceedings for Annual Meeting of The Japanese Pharmacological Society, 97, 3 - B

  Scientific journal


• Prefrontal contributions to mental resilience: Lessons from rodent studies of stress and antidepressant actions

  Ryota Shinohara, Tomoyuki Furuyashiki

  Individual variability of stress susceptibility led to the concept of stress resilience to adapt well upon stressors. However, the neural mechanisms of stress resilience and its relevance to antidepressant actions remain elusive. In rodents, chronic stress induces dendritic atrophy and decreases dendritic spine density in the medial prefrontal cortex (mPFC), recapitulating prefrontal alterations in depressive patients, and the mPFC promotes stress resilience. Whereas dopamine neurons projecting to the nucleus accumbens potentiated by chronic stress promote stress susceptibility, dopamine neurons projecting to the mPFC activated upon acute stress contribute to dendritic growth of mPFC neurons via dopamine D1 receptors, leading to stress resilience. Rodent studies have also identified the roles of prefrontal D1 receptors as well as D1 receptor-expressing mPFC neurons projecting to multiple subcortical areas and dendritic spine formation in the mPFC for the sustained antidepressant-like effects of low-dose ketamine. Thus, understanding the cellular and neural-circuit mechanism of prefrontal D1 receptor actions paves the way for bridging the gap between stress resilience and the sustained antidepressant-like effects. The mechanistic understanding of stress resilience might be exploitable for developing antidepressants based on a naturally occurring mechanism, thus safer than low-dose ketamine.

  Elsevier BV, Dec. 2022, Neuroscience Research, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Chronic social defeat stress increases the amounts of 12-lipoxygenase lipid metabolites in the nucleus accumbens of stress-resilient mice

  Satoshi Akiyama, Hirotaka Nagai, Shota Oike, Io Horikawa, Masakazu Shinohara, Yabin Lu, Takashi Futamura, Ryota Shinohara, Shiho Kitaoka, Tomoyuki Furuyashiki

  Abstract Severe and prolonged social stress induces mood and cognitive dysfunctions and precipitates major depression. Neuroinflammation has been associated with chronic stress and depression. Rodent studies showed crucial roles of a few inflammation-related lipid mediators for chronic stress-induced depressive-like behaviors. Despite an increasing number of lipid mediators identified, systematic analyses of synthetic pathways of lipid mediators in chronic stress models have not been performed. Using LC–MS/MS, here we examined the effects of chronic social defeat stress on multiple synthetic pathways of lipid mediators in brain regions associated with stress susceptibility in mice. Chronic social defeat stress increased the amounts of 12-lipoxygenase (LOX) metabolites, 12-HETE and 12-HEPE, specifically in the nucleus accumbens 1 week, but not immediately, after the last stress exposure. The increase was larger in stress-resilient mice than stress-susceptible mice. The S isomer of 12-HETE was selectively increased in amount, indicating the role of 12S-LOX activity. Among the enzymes known to have 12S-LOX activity, only Alox12 mRNA was reliably detected in the brain and enriched in brain endothelial cells. These findings suggest that chronic social stress induces a late increase in the amounts of 12S-LOX metabolites derived from the brain vasculature in the nucleus accumbens in a manner associated with stress resilience.

  Springer Science and Business Media LLC, Dec. 2022, Scientific Reports, 12(1) (1), 11385 - 11385, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Contextual fear conditioning regulates synapse-related gene transcription in mouse microglia.

  Zhiqian Yu, Mai Sakai, Hotaka Fukushima, Chiaki Ono, Yoshie Kikuchi, Ryuta Koyama, Ko Matsui, Tomoyuki Furuyashiki, Satoshi Kida, Hiroaki Tomita

  Microglia have been suggested to be involved in the underlying mechanism of conditional fear memory formation by regulating inflammatory cytokines. However, the mechanism linking microglia and neuronal activity related to fear conditioning remains unclear. This study characterized the transcription profile of microglia in a fear memory conditional mouse model. Compared with those in control mice microglia, the most significantly induced genes were synapse-related, whereas immune-related genes were reduced due to fear memory consolidation. Whilst the increased expression of synapse-related genes was reversed after fear memory extinction, that of immunological genes was not, strongly suggesting a connection between microglia, neurons, and a dysregulated immune response following contextual fear conditioning. Furthermore, in the hippocampal microglia, we found that the expression of neurotransmitter release regulators, γ-aminobutyric acid (GABA) receptor GABRB3 and synapsin 1/2, increased under fear memory consolidation and restored (decreased) after extinction. In addition, compared with the transcription profile in peripheral monocytes, few overlapping genes were not enriched in biological processes. Taken together, the identified conditional fear stress-induced changes in mouse microglial transcription profiles suggest that microglia-neuron communication mediates contextual fear conditioning.

  Aug. 2022, Brain research bulletin, 189, 57 - 68, English, International magazine

  Scientific journal


• ストレスは骨格筋のC/EBP経路を介して筋萎縮を促進する

  内山 奏, 平田 悠, 野村 和弘, Wijaya Hendy, 谷口 将之, 北岡 志保, 古屋敷 智之, 小川 渉

  (一社)日本筋学会, Aug. 2022, 日本筋学会学術集会プログラム・抄録集, 8回, 78 - 78, Japanese


• Brain fractalkine-CX3CR1 signalling is anti-obesity system as anorexigenic and anti-inflammatory actions in diet-induced obese mice.

  Namiko Kawamura, Goro Katsuura, Nobuko Yamada-Goto, Riho Nakama, Yuki Kambe, Atsuro Miyata, Tomoyuki Furuyashiki, Shuh Narumiya, Yoshihiro Ogawa, Akio Inui

  Fractalkine is one of the CX3C chemokine family, and it is widely expressed in the brain including the hypothalamus. In the brain, fractalkine is expressed in neurons and binds to a CX3C chemokine receptor 1 (CX3CR1) in microglia. The hypothalamus regulates energy homeostasis of which dysregulation is associated with obesity. Therefore, we examined whether fractalkine-CX3CR1 signalling involved in regulating food intake and hypothalamic inflammation associated with obesity pathogenesis. In the present study, fractalkine significantly reduced food intake induced by several experimental stimuli and significantly increased brain-derived neurotrophic factor (BDNF) mRNA expression in the hypothalamus. Moreover, tyrosine receptor kinase B (TrkB) antagonist impaired fractalkine-induced anorexigenic actions. In addition, compared with wild-type mice, CX3CR1-deficient mice showed a significant increase in food intake and a significant decrease in BDNF mRNA expression in the hypothalamus. Mice fed a high-fat diet (HFD) for 16 weeks showed hypothalamic inflammation and reduced fractalkine mRNA expression in the hypothalamus. Intracerebroventricular administration of fractalkine significantly suppressed HFD-induced hypothalamic inflammation in mice. HFD intake for 4 weeks caused hypothalamic inflammation in CX3CR1-deficient mice, but not in wild-type mice. These findings suggest that fractalkine-CX3CR1 signalling induces anorexigenic actions via activation of the BDNF-TrkB pathway and suppresses HFD-induced hypothalamic inflammation in mice.

  Jul. 2022, Scientific reports, 12(1) (1), 12604 - 12604, English, International magazine

  Scientific journal


• The transcription factor Hhex regulates inflammation-related genes in microglia.

  Risa Sakate, Masahiro Nishiyama, Yu Fukuda, Shiho Kitaoka, Tomoyuki Furuyashiki

  Microglia have diverse physiological and pathological functions. However, the transcriptional mechanisms remain elusive. Here we sought new transcription factors relevant to microglial functions from the microglial transcriptome of stressed mice and evaluated their roles in primary microglia. TLR2 and TLR4 agonists increased Rel, Atf3, and Cebpb and decreased Hhex in primary microglia as repeated social defeat stress. Although Hhex was not studied in microglia, TLR2 and TLR4 agonists decreased Hhex, and Hhex overexpression attenuated TLR4-increased expression of inflammation-related genes. These findings suggest that Hhex negatively regulates inflammation-related genes in microglia and that TLR2/4 activation reduces Hhex, facilitating TLR4-mediated neuroinflammation.

  Jul. 2022, Journal of pharmacological sciences, 149(3) (3), 166 - 171, English, Domestic magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Single-Shot 10K Proteome Approach: Over 10,000 Protein Identifications by Data-Independent Acquisition-Based Single-Shot Proteomics with Ion Mobility Spectrometry.

  Yusuke Kawashima, Hirotaka Nagai, Ryo Konno, Masaki Ishikawa, Daisuke Nakajima, Hironori Sato, Ren Nakamura, Tomoyuki Furuyashiki, Osamu Ohara

  The evolution of mass spectrometry (MS) and analytical techniques has led to the demand for proteome analysis with high proteome coverage in single-shot measurements. Focus has been placed on data-independent acquisition (DIA)-MS and ion mobility spectrometry as techniques for deep proteome analysis. We aimed to expand the proteome coverage by single-shot measurements using optimizing high-field asymmetric waveform ion mobility spectrometry parameters in DIA-MS. With our established proteome analysis system, more than 10,000 protein groups were identified from HEK293 cell digests within 120 min of MS measurement time. Additionally, we applied our approach to the analysis of host proteins in mouse feces and detected as many as 892 host protein groups (771 upregulated/121 downregulated proteins) in a mouse model of repeated social defeat stress (R-SDS) used in studying depression. Interestingly, 285 proteins elevated by R-SDS were related to mental disorders. The fecal host protein profiling by deep proteome analysis may help us understand mental illness pathologies noninvasively. Thus, our approach will be helpful for an in-depth comparison of protein expression levels for biological and medical research because it enables the analysis of highly proteome coverage in a single-shot measurement.

  Jun. 2022, Journal of proteome research, 21(6) (6), 1418 - 1427, English, International magazine

  Scientific journal


• Single-Cell RNA Sequencing Reveals a Distinct Immune Landscape of Myeloid Cells in Coronary Culprit Plaques Causing Acute Coronary Syndrome.

  Takuo Emoto, Hiroyuki Yamamoto, Tomoya Yamashita, Tomofumi Takaya, Takahiro Sawada, Shintaro Takeda, Masayuki Taniguchi, Naoto Sasaki, Naofumi Yoshida, Yoshihiro Saito, Tharini Sivasubramaniyam, Hiromasa Otake, Tomoyuki Furuyashiki, Clinton S Robbins, Hiroya Kawai, Ken-Ichi Hirata

  May 2022, Circulation, 145(18) (18), 1434 - 1436, English, International magazine


• ストレスはC/EBP-KLF15経路を介して筋萎縮を促進する

  内山 奏, 平田 悠, 野村 和弘, Wijaya Hendy, 北岡 志保, 古屋敷 智之, 小川 渉

  (一社)日本内分泌学会, Apr. 2022, 日本内分泌学会雑誌, 98(1) (1), 273 - 273, Japanese


• ストレスはC/EBP-KLF15経路を介して筋萎縮を促進する

  内山 奏, 平田 悠, 野村 和弘, Wijaya Hendy, 谷口 将之, 北岡 志保, 古屋敷 智之, 小川 渉

  (一社)日本糖尿病学会, Apr. 2022, 糖尿病, 65(Suppl.1) (Suppl.1), S - 185, Japanese


• C/EBP-KLF15経路はストレスによる筋萎縮に関与する

  内山 奏, 平田 悠, 野村 和弘, 北岡 志保, 古屋敷 智之, 小川 渉

  (一社)日本肥満学会, Mar. 2022, 肥満研究, 27(Suppl.) (Suppl.), 328 - 328, Japanese


• Deficient Autophagy in Microglia Aggravates Repeated Social Defeat Stress-Induced Social Avoidance.

  Mai Sakai, Zhiqian Yu, Ryo Hirayama, Masa Nakasato, Yoshie Kikuchi, Chiaki Ono, Hiroshi Komatsu, Miharu Nakanishi, Hatsumi Yoshii, David Stellwagen, Tomoyuki Furuyashiki, Masaaki Komatsu, Hiroaki Tomita

  Major depressive disorder (MDD) is associated with repeated exposure to environmental stress. Autophagy is activated under various stress conditions that are associated with several diseases in the brain. This study was aimed at elucidating the autophagy signaling changes in the prefrontal cortex (PFC) under repeated social defeat (RSD) to investigate the involvement of microglial autophagy in RSD-induced behavioral changes. We found that RSD stress, an animal model of MDD, significantly induced initial autophagic signals followed by increased transcription of autophagy-related genes (Atg6, Atg7, and Atg12) in the PFC. Similarly, significantly increased transcripts of ATGs (Atg6, Atg7, Atg12, and Atg5) were confirmed in the postmortem PFC of patients with MDD. The protein levels of the prefrontal cortical LC3B were significantly increased, whereas p62 was significantly decreased in the resilient but not in susceptible mice and patients with MDD. This indicates that enhanced autophagic flux may alleviate stress-induced depression. Furthermore, we identified that FKBP5, an early-stage autophagy regulator, was significantly increased in the PFC of resilient mice at the transcript and protein levels. In addition, the resilient mice exhibited enhanced autophagic flux in the prefrontal cortical microglia, and the autophagic deficiency in microglia aggravated RSD-induced social avoidance, indicating that microglial autophagy involves stress-induced behavioral changes.

  2022, Neural plasticity, 2022, 7503553 - 7503553, English, International magazine

  Scientific journal


• Relationship between dairy product intake and sense of coherence among middle and high school students in Japan.

  Kato Yoshiko, Kazumi Nagano, Chenghong Hu, Tomoyuki Furuyashiki

  Despite the growing attention toward the effects of dairy intake on stress and mental health, its relationship to psychological constructs that affect mental health remains poorly understood. We conducted a cross-sectional study (Study 1) and a longitudinal study (Study 2) to examine the association between food intake and stress resilience in Japanese middle and high school students. In Study 1, 865 participants (412 males and 453 females) completed the questionnaires. In Study 2, 109 students (51 males and 58 females) participated each year from 2016 to 2018. Dietary intake was assessed using a brief self-administered diet history questionnaire. Stress resilience was evaluated using a 13-item sense of coherence (SOC) questionnaire. Correlation coefficients were calculated in Study 1 to investigate the relationship between food group intake and SOC. In Study 2, a cross-lagged panel model was tested using structural equation modeling to investigate the effect of dairy product consumption on SOC. Study 1 revealed that only dairy product intake positively correlated with SOC and other food intake indicated no significant relationship. Study 2 indicated that augmented dairy product intake was positively associated with SOC. Among all foods, only dairy products were associated with SOC in adolescents. Although the association was weak, the longitudinal study confirmed that dairy consumption was associated with SOC. Randomized controlled trials are necessary to examine the causal relationship.

  2022, PloS one, 17(12) (12), e0279232, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Roles of synaptic mitochondrial regulations for stress susceptibility

  Numa Chisato, Nagai Hirotaka, Nagai Midori, Yamashita Tomomi, Kawashima Yusuke, Ohno Nobuhiko, Kataoka Yosky, Mimori-Kiyosue Yuko, Kato Taro, Furuyashiki Tomoyuki

  Chronic social stress induces neuronal dysfunctions in the medial prefrontal cortex (mPFC) for emotional and cognitive disturbances. However, the subcellular mechanism remains elusive. Here we examined ultrastructural and multi-omics changes in the mPFC in a mouse model of social defeat stress. Acute stress induced dendritic membrane deformation with mitochondrial swelling in mPFC neurons, leading to dendritic atrophy after chronic stress. Synaptic, but not bulk tissue, proteomes in the mPFC differentiated naïve and stressed mice and further uncovered two distinct states in stressed mice. Proteins involved in mitochondrial metabolic functions mostly decreased with chronic stress regardless of the synaptic proteomic state. By contrast, proteins responsible for mitochondrial homeostasis increased in stressed mice with a specific synaptic proteomic state associated with behavioral resilience to chronic stress. These findings suggest that the balance between mitochondrial metabolic dysfunction and its maintenance at mPFC synapses determines stress susceptibility in mice.

  Japanese Pharmacological Society, 2022, Proceedings for Annual Meeting of The Japanese Pharmacological Society, 95, 1-SS-13, Japanese


• Chronic social stress alters synaptic central metabolism for depression

  Nagai Hirotaka, Nagai Midori, Numa Chisato, Yamashita Tomomi, Kawashima Yusuke, Ohno Nobuhiko, Kataoka Yosky, Shimma Shuuichi, Mimori-Kiyosue Yuko, Kato Taro, Soga Tomoyoshi, Furuyashiki Tomoyuki

  Chronic social stress induces emotional and cognitive disturbances and is a risk for mental illness. Reduced neuronal activity in the medial prefrontal cortex (mPFC) underlies these behavioral abnormalities. However, the subcellular origin and process of this neuronal change remain elusive. Here we examined ultrastructural and multi-omics changes in the mPFC with social stress in mice. Social stress caused the loss of dendritic branches with morphological alterations of mitochondria and induced synaptic shrinkage selectively at mitochondria-containing synapses. Social stress deteriorated mitochondrial functions at synapses with altered mitochondrial proteome and central metabolism in the mPFC. Pharmacological manipulation targeting mitochondria attenuated the synaptic shrinkage and depression-related behaviors. These findings show that chronic social stress alters the central metabolism at mPFC synapses, leading to neuronal pathology and depression-related behaviors.

  Japanese Pharmacological Society, 2022, Proceedings for Annual Meeting of The Japanese Pharmacological Society, 95, 1-YIA-11, Japanese


• 【With/afterコロナ時代の新たな薬理学教育I:遠隔教育の実践と課題】「COVID-19に対する各大学の対応と生理学及び薬理学教育への影響に関する緊急合同調査」についての結果報告

  茂木 正樹, 古屋敷 智之, 田熊 一敞, 乙黒 兼一, 田中 智之, 南 雅文

  (公社)日本薬理学会, Nov. 2021, 日本薬理学雑誌, 156(6) (6), 324 - 329, Japanese


• The impact of stress on immune systems and its relevance to mental illness.

  Yuka Ishikawa, Tomoyuki Furuyashiki

  Stress due to adverse and demanding conditions alters immune functions. How innate and adaptive immune systems respond to stress and affect neural processes remains unclear. Rodent studies have demonstrated crucial roles of stress-induced immune responses for depressive- and anxiety-like behaviors. In the periphery, stress evokes the mobilization of neutrophils and monocytes to the circulation via sympathetic nerves and glucocorticoids. These myeloid cells are thought to promote depressive- and anxiety-like behaviors by infiltrating the brain's perivascular space, releasing cytokines, and affecting vascular endothelial functions. In the brain, stress activates microglia via innate immune receptors TLR2/4. The activated microglia in the medial prefrontal cortex secrete cytokines and alter neuronal morphology and activity in their vicinity. In subcortical brain areas, prostaglandin (PG) E2 released from the activated microglia attenuates the dopaminergic projection to the medial prefrontal cortex via PGE receptor EP1. These multiple actions of microglia promote depressive-like behavior in concert. These rodent findings may be translatable to depression that clinical studies have associated with brain and peripheral inflammations. Understanding causal relationships between immune and neural alterations under stress might be exploitable to develop inflammation-targeting therapeutics for mental illness.

  Oct. 2021, Neuroscience research, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Mobilization efficiency is critically regulated by fat via marrow PPARδ.

  Tomohide Suzuki, Shinichi Ishii, Masakazu Shinohara, Yuko Kawano, Kanako Wakahashi, Hiroki Kawano, Akiko Sada, Kentaro Minagawa, Michito Hamada, Satoru Takahashi, Tomoyuki Furuyashiki, Nguan Soon Tan, Toshimitsu Matsui, Yoshio Katayama

  The mobilization efficiency of hematopoietic stem/progenitor cells from bone marrow (BM) to circulation by granulocyte colony-stimulating factor (G-CSF) is dramatically dispersed in humans and mice with no mechanistic lead for poor mobilizers. The regulatory mechanism for mobilization efficiency by dietary fat was assessed in mice. Fat-free diet (FFD) for 2 weeks greatly increased mobilization compared to normal diet (ND). The BM mRNA level of peroxisome proliferator-activated receptor δ (PPARδ), a receptor for lipid mediators, was markedly up-regulated by G-CSF in mice fed with ND and displayed strong positive correlation with widely scattered mobilization efficiency. It was hypothesized that BM fat ligand for PPARδ might inhibit mobilization. The PPARδ agonist inhibited mobilization in mice fed with ND and enhanced mobilization by FFD. Treatment with the PPARδ antagonist and chimeric mice with PPARδ+/- BM showed enhanced mobilization. Immunohistochemical staining and flow cytometry revealed that BM PPARδ expression was enhanced by G-CSF mainly in mature/immature neutrophils. BM lipid mediator analysis revealed that G-CSF treatment and FFD resulted in the exhaustion of ω3-polyunsaturated fatty acids such as eicosapentaenoic acid (EPA). EPA induced the up-regulation of genes downstream of PPARδ, such as carnitine palmitoyltransferase-1α and angiopoietin-like protein 4 (Angptl4), in mature/immature neutrophils in vitro and inhibited enhanced mobilization in mice fed with FFD in vivo. Treatment of wild-type mice with the anti-Angptl4 antibody enhanced mobilization together with BM vascular permeability. Collectively, PPARδ signaling in BM mature/immature neutrophils induced by dietary fatty acids negatively regulates mobilization, at least partially, via Angptl4 production.

  Jun. 2021, Haematologica, 106(6) (6), 1671 - 1683, English, International magazine, Co-authored internationally

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Resting-state dopaminergic cell firing in the ventral tegmental area negatively regulates affiliative social interactions in a developmental animal model of schizophrenia.

  Hidekazu Sotoyama, Hisaaki Namba, Yutaro Kobayashi, Taku Hasegawa, Dai Watanabe, Ena Nakatsukasa, Kenji Sakimura, Tomoyuki Furuyashiki, Hiroyuki Nawa

  Hyperdopaminergic activities are often linked to positive symptoms of schizophrenia, but their neuropathological implications on negative symptoms are rather controversial among reports. Here, we explored the regulatory role of the resting state-neural activity of dopaminergic neurons in the ventral tegmental area (VTA) on social interaction using a developmental rat model for schizophrenia. We prepared the model by administering an ammonitic cytokine, epidermal growth factor (EGF), to rat pups, which later exhibit the deficits of social interaction as monitored with same-gender affiliative sniffing. In vivo single-unit recording and microdialysis revealed that the baseline firing frequency of and dopamine release from VTA dopaminergic neurons were chronically increased in EGF model rats, and their social interaction was concomitantly reduced. Subchronic treatment with risperidone ameliorated both the social interaction deficits and higher frequency of dopaminergic cell firing in this model. Sustained suppression of hyperdopaminergic cell firing in EGF model rats by DREADD chemogenetic intervention restored the event-triggered dopamine release and their social behaviors. These observations suggest that the higher resting-state activity of VTA dopaminergic neurons is responsible for the reduced social interaction of this schizophrenia model.

  Springer Science and Business Media LLC, Apr. 2021, Translational psychiatry, 11(1) (1), 236 - 236, English, International magazine

  Scientific journal


• Correlation Between Lactic Acid Bacteria Beverage Intake and Stress Resilience.

  Yoshiko Kato, Yukari Shimomura, Yoshihiro Takada, Tomoyuki Furuyashiki

  We investigated the effect of lactic acid bacteria-containing beverage intake on the level of resilience against stress in male university students. Forty male university students were recruited into the study and randomly assigned into two groups. They were instructed to consume lactic acid bacteria-containing beverage or water twice a day for 28 days. The level of stress resilience, stress reaction, and anxiety were evaluated by a series of questionnaires conducted at three time points (T1: day 0, T2: day 14, and T3: day 28). The stress response was also assessed by measuring their salivary amylase levels. The variance analysis of each group showed a significant increase in stress resilience at T3 compared with T1 in the group of participants who consumed the lactic acid bacteria-containing beverage. Our results suggest that lactic acid bacteria-containing beverage intake could affect resilience against stress positively.

  Apr. 2021, The Kobe journal of medical sciences, 67(1) (1), E1-E6, English, Domestic magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• [Responses to the COVID-19 pandemic and its impacts on pharmacology education in the universities and colleges in Japan: nationwide emergency survey jointly conducted by the Physiological Society of Japan and the Japanese Pharmacological Society].

  Masaki Mogi, Tomoyuki Furuyashiki, Kazuhiro Takuma, Ken-Ichi Otsuguro, Satoshi Tanaka, Masabumi Minami

  With the spread of new coronavirus infections (COVID-19), universities/colleges have transformed their educational format from conventional group education to distance learning. In order to share information on the new educational format among the members of the society, the Physiological Society of Japan and the Japanese Pharmacological Society (JPS) jointly conducted the "Emergency Joint Survey on Responses of Universities to COVID-19 and Its Impact on Physiology and Pharmacology Education". The JPS surveyed pharmacology departments/divisions at schools of pharmacy, medicine, dentistry, and veterinary medicine in 202 universities (response rate 89%) from August to September 2020. 85% of the universities changed the lecture method, and 70% changed the practical training. 30%, 30%, and 40% of the lectures were live, on-demand, and mixed (combination of live and on-demand) lectures, respectively. 25% of the practical training was live or a combination of live and on-demand lectures, and 45% was on-demand delivery. There are many problems to do online methods such as stable network environment, lack of the reality for students and difficulty of the check of their understanding. On the other hand, there are unexpected benefits in online methods such as anytime learning, an increase in questions from students and repeatable learning. More than 60% considered employing the newly introduced educational styles even after the pandemic. Students' mental health problems and disruption of daily rhythms, quality assurance of online education, and copyright issues were also concerned. Pharmacology education faces a significant turning point in introducing and improving distance learning with or post the COVID-19 pandemic.

  2021, Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 156(6) (6), 324 - 329, Japanese, Domestic magazine

  Scientific journal


• Hop Bitter Acids Increase Hippocampal Dopaminergic Activity in a Mouse Model of Social Defeat Stress.

  Yasuhisa Ano, Shiho Kitaoka, Rena Ohya, Keiji Kondo, Tomoyuki Furuyashiki

  As daily lifestyle is closely associated with mental illnesses, diet-based preventive approaches are receiving attention. Supplementation with hop bitter acids such as iso-α-acids (IAA) and mature hop bitter acids (MHBA) improves mood states in healthy older adults. However, the underlying mechanism remains unknown. Since acute oral consumption with IAA increases dopamine levels in hippocampus and improves memory impairment via vagal nerve activation, here we investigated the effects of chronic administration of hop bitter acids on the dopaminergic activity associated with emotional disturbance in a mouse model of repeated social defeat stress (R-SDS). Chronic administration of IAA and MHBA significantly increased dopaminergic activity based on the dopamine metabolite to dopamine ratio in the hippocampus and medial prefrontal cortex following R-SDS. Hippocampal dopaminergic activity was inversely correlated with the level of R-SDS-induced social avoidance with or without IAA administration. Therefore, chronic treatment with hop bitter acids enhances stress resilience-related hippocampal dopaminergic activity.

  Dec. 2020, International journal of molecular sciences, 21(24) (24), English, International magazine

  Scientific journal


• Repeated social defeat stress induces neutrophil mobilization in mice: maintenance after cessation of stress and strain-dependent difference in response.

  Yuka Ishikawa, Shiho Kitaoka, Yuko Kawano, Shinichi Ishii, Tomohide Suzuki, Kanako Wakahashi, Taro Kato, Yoshio Katayama, Tomoyuki Furuyashiki

  BACKGROUND AND PURPOSE: Inflammation has been associated with stress-related mental disturbances. Rodent studies have reported that blood-borne cytokines are crucial for stress-induced changes in emotional behaviours. However, the roles and regulation of leukocytes in chronic stress remain unclear. EXPERIMENTAL APPROACH: Adult male C57BL/6N mice were subjected to repeated social defeat stress (R-SDS) with two protocols which differed in stress durations, stress cycles, and housing conditions, followed by the social interaction test. The numbers of leukocyte subsets in the bone marrow, spleen, and blood were determined by flow cytometry shortly after or several days after R-SDS. These leukocyte changes were studied in two strains of mice with different stress susceptibility, C57BL/6N and BALB/c mice. KEY RESULTS: R-SDS with both protocols similarly induced social avoidance in C57BL/6N mice. In the bone marrow, neutrophils and monocytes were increased, and T cells, B cells, NK cells, and dendritic cells were decreased with both protocols. In the blood, neutrophils and monocytes were increased with both protocols, whereas T cells, B cells, NK cells, and dendritic cells were decreased with one of these. Neutrophils and monocytes were also increased in the spleen. Changes in the bone marrow and increased levels of circulating neutrophils were maintained for 6 days after R-SDS. BALB/c mice showed greater social avoidance and increase in circulating neutrophils than C57BL/6N mice. CONCLUSION AND IMPLICATIONS: In two strains of mice, chronic stress induced neutrophil mobilization and its maintenance. These effects were strain-related and may contribute to the pathology of mental illness.

  Jul. 2020, British journal of pharmacology, 178(4) (4), 827 - 844, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• The role of prostaglandin E₂ in environmental factors of psychiatric disorders

  Hida Hirotake, Mouri Akihiro, Takasu Mitsuhira, Muto Rina, Uchida Mizuki, Furuyashiki Tomoyuki, Narumiya Shuh, Nabeshima Toshitaka, Yamada Kiyofumi, Yoshimi Akira, Ozaki Norio, Noda Yukihiro

  We investigated the possibility of prostaglandin E₂ (PGE₂) as one of common molecules associated with vulnerability to neurodevelopmental disruptions induced by environmental factors. PGE₂ levels in whole brain were significantly increased after exposure to viral infection [injection of polyinosinic-polycytidylic acid (polyI:C)], hypoxia (exposure to CO₂), and neglect (separation from the dams) in postnatal day (PD) 2, compared to those after non-exposure. The mice administered polyI:C during PD 2-6 exhibited the impairment of sociality, object recognition memory, and pre-pulse inhibition (PPI) in adult at PD 70, and further, significant decreased spine density of the mPFC in adult mice. Exposure to CO₂ at PD 2 and separation from dams during PD 2-21 exhibited the impairment of PPI and decrease of spine density in adult mice. These behavioral impairments induced by administration of polyI:C were recovered by an inhibition of PGE₂-EP1 (PGE₂ receptor subtype) and of cyclooxygenase (COX).  Our findings suggest that PGE₂ is one of potential common molecules associated with vulnerability to neurodevelopmental disruptions induced by environmental factors, and PGE₂ plays a crucial role in the development of behavioral and neuronal impairments, which are associated with activation of PGE₂-EP1.

  Japanese Pharmacological Society, 2020, Proceedings for Annual Meeting of The Japanese Pharmacological Society, 93, 3-P-282, Japanese


• Stress-induced sleep-like inactivity modulates stress susceptibility in mice.

  Midori Nagai, Hirotaka Nagai, Chisato Numa, Tomoyuki Furuyashiki

  Severe environmental and social stress induces dysregulation of sleep along with mood and cognitive disturbances. However, the role and mechanism of this sleep dysregulation remain elusive. Here we evaluated sleep-like inactivity measured by voluntary movements and its relationship to social behaviors in mice without or with social defeat stress as well as the stressed mice with subsequent sleep deprivation. Social defeat stress immediately induced sleep-like inactivity with decreased body temperature. In the social interaction test, the control mice showed high social interest and its correlation with social sniffing intensity, the latter of which indicates positive valence of social sniffing. After the stress, these social characteristics were maintained in stress-resilient mice, but disrupted in stress-susceptible mice, leading to social avoidance. Sleep deprivation after the stress decreased social sniffing intensity along with reduced social interest, but enhanced the exploratory activity with the positive valence of social sniffing. We also found by c-Fos immunohistochemistry that the stress activated sleep-related brain regions, the dorsomedial hypothalamus and ventrolateral periaqueductal gray. Collectively, these findings show that stress activates sleep-related brain regions and induces sleep-like inactivity, contributing to multiple roles of stress-induced sleep for social behaviors.

  2020, Scientific reports, in press(1) (1), 19800 - 19800, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Social defeat stress-specific increase in c-Fos expression in the extended amygdala in mice: Involvement of dopamine D1 receptor in the medial prefrontal cortex

  Chisato Numa, Hirotaka Nagai, Masayuki Taniguchi, Midori Nagai, Ryota Shinohara, Tomoyuki Furuyashiki

  We recently reported that dopamine D1 receptor in the medial prefrontal cortex (mPFC) is activated by subthreshold social defeat stress and suppresses the induction of depressive-like behavior in mice. However, which mPFC projection(s) mediates this antidepressant-like effect remains poorly understood. Here we show that social defeat stress specifically increased c-Fos expression, a marker for neuronal activity, in distinct brain regions involved in emotional regulation, relative to novelty-induced exploration. Among these brain areas, D1 knockdown in the mPFC decreased social defeat stress-induced c-Fos expression in the interstitial nucleus of the posterior limb of the anterior commissure (IPAC), a subregion of the extended amygdala. Using retrograde adeno-associated virus vectors and transgenic mice expressing Cre recombinase under the D1 promoter, we also found that D1-expressing deep-layer pyramidal neurons in the mPFC send direct projections to the IPAC. These findings indicate that social defeat stress specifically activates neurons in distinct brain areas, among which the IPAC is regulated by dopamine D1 receptor in the mPFC perhaps through direct projections. Thus, this study provides hints toward identifying neural circuits that underlie antidepressant-like effects of stress-induced dopamine D1 receptor signaling in the mPFC.

  Springer Science and Business Media LLC, Dec. 2019, Scientific Reports, 9(1) (1), 16670 - 16670, English, International magazine, Co-authored internationally

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Roles of Toll-like receptor 2/4, monoacylglycerol lipase, and cyclooxygenase in social defeat stress-induced prostaglandin E2 synthesis in the brain and their behavioral relevance

  Xiang Nie, Shiho Kitaoka, Masakazu Shinohara, Akira Kakizuka, Shuh Narumiya, Tomoyuki Furuyashiki

  Inflammation in the brain and periphery has been associated with stress-related pathology of mental illness. We have shown that prostaglandin (PG) E2, an arachidonic acid-derived lipid mediator, and innate immune receptors Toll-like receptor (TLR) 2/4 are crucial for repeated stress-induced behavioral changes in rodents. However, how the stress induces PGE2 synthesis in the brain and whether TLR2/4 are involved in the PGE2 synthesis remain unknown. Using mice lacking TLR2 and TLR4 in combination, here we show that social defeat stress (SDS) induced the PGE2 synthesis in subcortical, but not cortical, tissues in a TLR2/4-dependent manner. It is known that PGE2 in the brain is mainly derived by monoacylglycerol lipase (MAGL)-mediated conversion of endocannabinoid 2-arachidonoylglycerol to free-arachidonic acid, a substrate for cyclooxygenase (COX) for PGE2 synthesis. We found that TLR2/4 deletion reduced the mRNA expression of MAGL and COX1 in subcortical tissues after repeated SDS. Perturbation of MAGL and COX1 as well as COX2 abolished SDS-induced PGE2 synthesis in subcortical tissues. Furthermore, systemic administration of JZL184, an MAGL inhibitor, abolished repeated SDS-induced social avoidance. These results suggest that SDS induces PGE2 synthesis in subcortical regions of the brain via the MAGL-COX pathway in a TLR2/4-dependent manner, thereby leading to social avoidance.

  Springer Science and Business Media LLC, Dec. 2019, Scientific Reports, 9(1) (1), 17548 - 17548, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Three-dimensional fluorescence imaging using the transport of intensity equation

  Sudheesh K. Rajput, Manoj Kumar, Xiangyu Quan, Mitsuhiro Morita, Tomoyuki Furuyashiki, Yasuhiro Awatsuji, Enrique Tajahuerce, Osamu Matoba

  We propose a nonscanning three-dimensional (3-D) fluorescence imaging technique using the transport of intensity equation (TIE) and free-space Fresnel propagation. In this imaging technique, a phase distribution corresponding to defocused fluorescence images with a point-light-source-like shape is retrieved by a TIE-based phase retrieval algorithm. From the obtained phase distribution, and its corresponding amplitude distribution, of the defocused fluorescence image, various images at different distances can be reconstructed at the desired plane after Fresnel propagation of the complex wave function. Through the proposed imaging approach, the 3-D fluorescence imaging can be performed in multiple planes. The fluorescence intensity images are captured with the help of an electrically tunable lens; hence, the imaging technique is free from motion artifacts. We present experimental results corresponding to microbeads and a biological sample to demonstrate the proposed 3-D fluorescence imaging technique.

  SPIE-Intl Soc Optical Eng, Nov. 2019, Journal of Biomedical Optics, 25(03) (03), 1 - 1, English, International magazine

  [Refereed]

  Scientific journal


• Neural mechanisms underlying adaptive and maladaptive consequences of stress: Roles of dopaminergic and inflammatory responses

  Tomoyuki Furuyashiki, Shiho Kitaoka

  Stress caused by adverse and demanding conditions, a risk factor for mental illnesses, induces adaptive or maladaptive neural and behavioral consequences, depending on the conditions. Studies using rodent stress models have revealed multiple mechanisms related to dopamine and inflammation for stress-induced neural and behavioral changes. Thus, repeated stress alters activities of ventral tegmental area dopamine neurons projecting to the nucleus accumbens and the medial prefrontal cortex in distinct manners. In the nucleus accumbens, repeated stress decreases activities of D1 receptor-expressing neurons. In the medial prefrontal cortex, single stress increases dopamine D1 receptor signaling, leading to dendritic hypertrophy of excitatory neurons and stress resilience. These changes are attenuated with repetition of stress via prostaglandin E2 , an inflammation-related lipid mediator. Repeated stress activates microglia in the medial prefrontal cortex and the hippocampus. Innate immune receptors, such as the toll-like receptor 2/4 and P2X7, are crucial for repeated stress-induced microglial activation, leading to neural and behavioral changes through proinflammatory cytokines. In addition, repeated stress induces monocyte infiltration to the brain, and impairs the blood-brain barrier in the nucleus accumbens, leading to cytokine leakage to the brain. These monocyte-derived responses are involved in stress-induced behavioral changes. These findings show crucial roles of the accumbal and prefrontal dopamine pathways and inflammatory responses in the brain and body to direct adaptive and maladaptive consequences of stress, and pave the way for identifying a neural origin of stress and understanding the stress-related pathology of mental illnesses.

  Wiley, Nov. 2019, Psychiatry and Clinical Neurosciences, 73(11) (11), 669 - 675, English, International magazine

  [Refereed]

  Scientific journal


• The Lacto-Tetrapeptide Gly-Thr-Trp-Tyr, β-Lactolin, Improves Spatial Memory Functions via Dopamine Release and D1 Receptor Activation in the Hippocampus.

  Tatsuhiro Ayabe, Yasuhisa Ano, Rena Ohya, Shiho Kitaoka, Tomoyuki Furuyashiki

  SCOPE: Peptides containing tryptophan-tyrosine sequences, including the lacto-tetrapeptide glycine-threonine-tryptophan-tyrosine (GTWY) and β-lactolin, from β-lactoglobulin in whey enzymatic digestion, enhance hippocampus-dependent memory functions, which are blocked by the systemic administration of dopamine D1-like antagonist. In this study, we investigated the role of the hippocampal dopaminergic system in the memory-enhancing effect of β-lactolin. METHODS AND RESULTS: The results of in vivo microdialysis revealed that oral administration of β-lactolin increased the extracellular concentration of dopamine in the hippocampus and enhanced both spatial working memory, as measured in the Y-maze test, and spatial reference memory, as measured in the novel object location test. These memory-enhancing effects of β-lactolin, but not the baseline memory functions, were impaired by the knockdown of the dopamine D1 receptor subtype in the hippocampus. β-Lactolin also enhanced object memory, as measured by the novel object recognition test. However, D1 knockdown in the hippocampus spared this memory function either with or without the administration of β-lactolin. CONCLUSIONS: The present results indicate that oral administration of β-lactolin increases dopamine release and D1 receptor signaling in the hippocampus, thereby enhancing spatial memory, but it may improve object memory via a separate mechanism.

  Oct. 2019, Nutrients, 11(10) (10), English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Roles of multiple lipid mediators in stress and depression

  Tomoyuki Furuyashiki, Satoshi Akiyama, Shiho Kitaoka

  Prolonged or excessive stress may induce emotional and cognitive disturbances, and is a risk factor for mental illnesses. Using rodent chronic stress models of depression, roles of multiple lipid mediators related to inflammation have been revealed in chronic stress-induced emotional alterations. Prostaglandin (PG) E2, an arachidonic acid (AA)-derived lipid mediator, and its receptor subtype EP1 mediate depression-like behavior induced by repeated social defeat stress through attenuating prefrontal dopaminergic activity. Repeated social defeat stress activates microglia through innate immune receptors, and induces PGE2 synthesis through cyclooxygenase-1, a prostaglandin synthase enriched in microglia. PGD2, another AA-derived lipid mediator, has been implicated in depression induced by chronic stress, although either pro-depressive or anti-depressive actions have been reported. Chronic stress up-regulates hippocampal expression of 5-lipoxygenase, hence synthesis of cysteinyl leukotrienes, thereby inducing depression through their receptors. Consistent with beneficial effects of n-3 fatty acids in the diet of depressive patients, resolvins—a novel class of pro-resolving lipid mediators—in the brain attenuate neuroinflammation-associated depression. These findings in animal models of depression offer lipid mediators and related molecules as novel therapeutic targets for treating depression. To translate these findings into clinics, translational biomarkers to visualize lipid mediator profiles in depressive patients need to be established.

  Oxford University Press (OUP), Aug. 2019, International Immunology, 31(9) (9), 579 - 587, English, International magazine

  [Refereed]

  Scientific journal


• Leucine-Histidine Dipeptide Attenuates Microglial Activation and Emotional Disturbances Induced by Brain Inflammation and Repeated Social Defeat Stress.

  Yasuhisa Ano, Masahiro Kita, Shiho Kitaoka, Tomoyuki Furuyashiki

  The number of patients with mental illnesses is rapidly increasing, and daily lifestyle is closely associated with the development of symptoms. It is suggested that inflammatory molecules derived from microglia play crucial roles for the pathophysiology of depression. In the present study, we discovered that leucine-histidine (LH) dipeptide suppressed activation of primary microglia. The effects of LH dipeptide orally administered were measured using tail suspension test (TST) in mice injected with lipopolysaccharide and social interaction test in mice received social defeat stress. LH dipeptide reduced pro-inflammatory cytokines upon stimulation in microglia. Orally administered LH dipeptide was delivered to the brain and suppressed the production of pro-inflammatory cytokines in the brain and concomitant depression-like behavior in the TST. Moreover, oral administration of LH dipeptide suppressed the induction of depression- and anxiety-like behaviors induced by repeated social defeat stress. These results indicate that LH dipeptide suppressed the activation of microglia and ameliorated depression-associated emotional disturbances. Further, we found that LH dipeptide was abundant in various fermented products. Together with previous epidemiological reports that daily intake of these fermented foods is negatively associated with the incidence of psychiatric diseases, our findings suggest that food rich in LH dipeptide may improve mental health.

  Aug. 2019, Nutrients, 11(9) (9), 2161, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Improvement of PTSD-like behavior by the forgetting effect of hippocampal neurogenesis enhancer memantine in a social defeat stress paradigm.

  Rie Ishikawa, Chiaki Uchida, Shiho Kitaoka, Tomoyuki Furuyashiki, Satoshi Kida

  Post-traumatic stress disorder (PTSD) is a psychiatric disorder associated with memories of traumatic experiences. Recent studies have shown that the forgetting of contextual fear memory is promoted via increased adult hippocampal neurogenesis induced by neurogenesis enhancers, such as memantine (MEM) and exercise, raising the possibility that neurogenesis enhancers improve PTSD by facilitating the forgetting of traumatic memory. On the other hand, repeated exposure to social defeat (SD) stress by aggressor mice induces social avoidance behavior to the aggressor and chronic anxiety-like behavior. In this study, we assumed this SD stress paradigm as a PTSD-like model and examined the effects of treatment with neurogenesis enhancer MEM on SD stress-induced PTSD-like behavior. Male C57BL/6 mice received SD stress for 10 consecutive days and were assessed for social avoidance memory to the aggressor (memory of aggressor mice) and anxiety-like behavior using social interaction and elevated zero maze tasks. Consistent with previous studies, SD mice formed social avoidance memory and exhibited increased anxiety-like behavior. Importantly, subsequent MEM treatment (once a week for 4 weeks) significantly reduced social avoidance behavior, suggesting that MEM-treated SD mice showed forgetting of social avoidance memory. Interestingly, MEM-treated SD mice showed comparable anxiety-like behavior with control mice that were not exposed to SD stress. Moreover, MEM-treated SD mice showed no reinstatement of social avoidance memory following single re-exposure to the aggressor. Our findings suggest that neurogenesis enhancer not only enhanced the forgetting of traumatic memory but also improved PTSD (anxiety)-like behavior.

  Aug. 2019, Molecular brain, 12(1) (1), 68 - 68, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Social defeat stress induces phosphorylation of extracellular signal-regulated kinase in the leptomeninges in mice

  Satoshi Okamura, Hirotaka Nagai, Chisato Numa, Midori Nagai, Ryota Shinohara, Tomoyuki Furuyashiki

  AIMS: Animal studies using various stress models have shown that excessive environmental stress induces depression? and anxiety?like behaviors through inflammatory responses in the brain and periphery. Although the leptomeningeal cells have multiple functions related to inflammatory responses in the brain, whether environmental stress influences the leptomeninges remains unknown. In this study, we aimed to examine phosphorylation of the extracellular signal-regulated kinase (ERK) in the leptomeninges. METHODS: We subjected C57BL/6 male mice to a single episode of social defeat stress and analyzed the expression of phosphorylated ERK in the leptomeninges by immunohistochemistry. RESULTS: Social defeat stress in mice induced phosphorylation of ERK in the leptomeninges, adjacent to vascular endothelial cells and the glia limitans. This ERK phosphorylation was maintained for at least one hour after the stress. CONCLUSIONS: This study shows the effect of environmental stress on the leptomeninges for the first time and paves the way for elucidating its functional role in stress-induced changes in neural functions.

  Wiley, Jun. 2019, Neuropsychopharmacology Reports, 39(2) (2), 134 - 139, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Iso-α-acids, the bitter components of beer, improve hippocampus-dependent memory through vagus nerve activation.

  Ano Y, Hoshi A, Ayabe T, Ohya R, Uchida S, Yamada K, Kondo K, Kitaoka S, Furuyashiki T

  Iso-α-acids (IAAs) are hop-derived bitter acids of beer. Epidemiologic studies suggest that moderate alcohol consumption is beneficial for cognitive function, but they do not show the ingredients in alcoholic beverages. Previously, we reported that long-term consumption of IAAs prevents inflammation and Alzheimer pathologies in mice, but their effects on cognitive function have not been evaluated. In the present study, we demonstrated that the consumption of IAAs improves spatial and object recognition memory functions not only in normal Crl:CD1(ICR) male mice but also in mice with pharmacologically induced amnesia. IAA consumption increased the total and extracellular levels of dopamine in the hippocampus of mice and Sprague-Dawley male rats, respectively. Dopamine D1 receptor antagonist treatment and knockdown of dopamine D1 receptor expression in the hippocampus attenuated IAA-induced spatial memory improvement. Furthermore, vagotomy attenuated the effects of IAAs in improving spatial and object recognition memory functions and increasing the total level of dopamine in the hippocampus. These results suggest that the consumption of IAAs activates dopamine D1 receptor-signaling in the hippocampus in a vagus nerve-dependent manner and, consequently, improves spatial and object recognition memory functions. Vagal activation with food components including IAAs may be an easy and safe approach to improve cognitive functions.-Ano, Y., Hoshi, A., Ayabe, T., Ohya, R., Uchida, S., Yamada, K., Kondo, K., Kitaoka, S., Furuyashiki, T. Iso-α-acids, the bitter components of beer, improve hippocampus-dependent memory through vagus nerve activation.

  Apr. 2019, FASEB J, 33(4) (4), 4987 - 4995, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Tryptophan-tyrosine dipeptide improves memory modulating the dopamine system.

  Ano Y, Ayabe T, Ohya R, Kondo K, Kitaoka S, Furuyashiki T

  Tryptophan-tyrosine (WY)-related peptides including the β-lactopeptide of the glycine-threonine-tryptophan-tyrosine peptide, β-lactolin, improve spatial memory. However, whether and how the WY dipeptide as the core sequence in WY-related peptides improves memory functions has not been investigated. This study assessed the pharmacological effects of the WY dipeptide on memory impairment to elucidate the mechanisms. Here, we showed that oral administration of dipeptides of WY, tryptophan-methionine (WM), tryptophan-valine, tryptophan-leucine, and tryptophan-phenylalanine improved spontaneous alternation of the Y-maze test in scopolamine-induced amnesic mice. In contrast, tyrosine-tryptophan, methionine-tryptophan, tryptophan, tyrosine, and methionine had no effect. These results indicated that the conformation of dipeptides with N-terminal tryptophan is required for their memory improving effects. WY dipeptide inhibited the monoamine oxidase B activity in vitro and increased dopamine levels in the hippocampus and frontal cortex, whereas tryptophan did not cause these effects. In addition, the treatment with SCH-23390, a dopamine D1-like receptor antagonist, and the knockdown of the hippocampal dopamine D1 receptor partially attenuated the memory improvement induced by the WY dipeptide. Importantly, WY dipeptide improved the spontaneous alternations of the Y-maze test in aged mice. These results suggest that the WY dipeptide restores memory impairments by augmenting dopaminergic activity. The development of supplements rich in these peptides might help to prevent age-related cognitive decline.

  Feb. 2019, Nutrients, 11(2) (2), E348, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Repeated social defeat stress impairs attentional set shifting irrespective of social avoidance and increases female preference associated with heightened anxiety

  Shu Higashida, Hirotaka Nagai, Kazuki Nakayama, Ryota Shinohara, Masayuki Taniguchi, Midori Nagai, Takatoshi Hikida, Satoshi Yawata, Yukio Ago, Shiho Kitaoka, Shuh Narumiya, Tomoyuki Furuyashiki

  Repeated social defeat stress (R-SDS) induces multiple behavioral changes in mice. However, the relationships between these behavioral changes were not fully understood. In the first experiment, to examine how the social avoidance is related to R-SDS-impaired behavioral flexibility, 10-week-old male C57BL/6N mice received R-SDS followed by the social interaction test and the attentional set shifting task. R-SDS impaired attentional set shifting irrespective of the development of social avoidance. In the second experiment, to examine whether R-SDS affects sexual preference and how this behavioral change is related to the social avoidance and R-SDS-heightened anxiety, another group of 10-week-old male C57BL/6N mice were subjected to R-SDS followed by the social interaction test, the female encounter test and the elevated plus maze test. The anxiety was heightened in the defeated mice without social avoidance, but not in those which showed social avoidance. Furthermore, female preference was increased specifically in the defeated mice which showed heightened anxiety, but was not related to the level of social avoidance. Together, these results showed that attentional set shifting is more sensitive to R-SDS than social interaction, and that female preference is affected by R-SDS in association with heightened anxiety rather than the social avoidance.

  Springer Science and Business Media LLC, Dec. 2018, Scientific Reports, 8(1) (1), 10454 - 10454, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Ulk2 controls cortical excitatory-inhibitory balance via autophagic regulation of p62 and GABAA receptor trafficking in pyramidal neurons.

  Sumitomo A, Yukitake H, Hirai K, Horike K, Ueta K, Chung Y, Warabi E, Yanagawa T, Kitaoka S, Furuyashiki T, Narumiya S, Hirano T, Niwa M, Sibille E, Hikida T, Sakurai T, Ishizuka K, Sawa A, Tomoda T

  Autophagy plays an essential role in intracellular degradation and maintenance of cellular homeostasis in all cells, including neurons. Although a recent study reported a copy number variation of Ulk2, a gene essential for initiating autophagy, associated with a case of schizophrenia (SZ), it remains to be studied whether Ulk2 dysfunction could underlie the pathophysiology of the disease. Here we show that Ulk2 heterozygous (Ulk2+/-) mice have upregulated expression of sequestosome-1/p62, an autophagy-associated stress response protein, predominantly in pyramidal neurons of the prefrontal cortex (PFC), and exhibit behavioral deficits associated with the PFC functions, including attenuated sensorimotor gating and impaired cognition. Ulk2+/- neurons showed imbalanced excitatory-inhibitory neurotransmission, due in part to selective down-modulation of gamma-aminobutyric acid (GABA)A receptor surface expression in pyramidal neurons. Genetically reducing p62 gene dosage or suppressing p62 protein levels with an autophagy-inducing agent restored the GABAA receptor surface expression and rescued the behavioral deficits in Ulk2+/- mice. Moreover, expressing a short peptide that specifically interferes with the interaction of p62 and GABAA receptor-associated protein, a protein that regulates endocytic trafficking of GABAA receptors, also restored the GABAA receptor surface expression and rescued the behavioral deficits in Ulk2+/- mice. Thus, the current study reveals a novel mechanism linking deregulated autophagy to functional disturbances of the nervous system relevant to SZ, through regulation of GABAA receptor surface presentation in pyramidal neurons.

  Sep. 2018, Hum Mol Genet, 27(18) (18), 3165 - 3176, English, International magazine

  [Refereed]

  Scientific journal


• The innate immune receptors TLR2/4 mediate repeated social defeat stress-induced social avoidance through prefrontal microglial activation.

  Nie X, Kitaoka S, Tanaka K, Segi-Nishida E, Imoto Y, Ogawa A, Nakano F, Tomohiro A, Nakayama K, Taniguchi M, Mimori-Kiyosue Y, Kakizuka A, Narumiya S, Furuyashiki T

  Repeated environmental stress has been proposed to induce neural inflammation together with depression and anxiety. Innate immune receptors, such as Toll-like receptors (TLRs), are activated by exogenous or endogenous ligands to evoke inflammation. Here we show that the loss of TLR2 and TLR4 (TLR2/4) abolished repeated social defeat stress (R-SDS)-induced social avoidance and anxiety in mice. TLR2/4 deficiency mitigated R-SDS-induced neuronal response attenuation, dendritic atrophy, and microglial activation in the medial prefrontal cortex (mPFC). Furthermore, mPFC microglia-specific TLR2/4 knockdown blocked social avoidance. Transcriptome analyses revealed that R-SDS induced IL-1α and TNF-α in mPFC microglia in a TLR2/4-dependent manner, and antibody blockade of these cytokines in the mPFC suppressed R-SDS-induced social avoidance. These results identify TLR2/4 as crucial mediators of R-SDS-induced microglial activation in the mPFC, which leads to neuronal and behavioral changes through inflammation-related cytokines, highlighting unexpected pivotal roles of innate immunity in the mPFC in repeated environmental stress-induced behavioral changes. VIDEO ABSTRACT.

  Aug. 2018, Neuron, 99(3) (3), 464 - 479, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Dopamine D1 receptor subtype mediates acute stress-induced dendritic growth in excitatory neurons of the medial prefrontal cortex and contributes to suppression of stress susceptibility in mice

  R Shinohara, M Taniguchi, A T Ehrlich, K Yokogawa, Y Deguchi, Y Cherasse, M Lazarus, Y Urade, A Ogawa, S Kitaoka, A Sawa, S Narumiya, T Furuyashiki

  Springer Science and Business Media LLC, Aug. 2018, Molecular Psychiatry, 23(8) (8), 1717 - 1730, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• EP2 receptor plays pivotal roles in generating mechanical hyperalgesia after lengthening contractions

  H. Ota, K. Katanosaka, S. Murase, T. Furuyashiki, S. Narumiya, K. Mizumura

  Blackwell Munksgaard, Mar. 2018, Scandinavian Journal of Medicine and Science in Sports, 28(3) (3), 826 - 833, English

  [Refereed]

  Scientific journal


• 神経発達脆弱性因子による成体期の精神機能への影響 PGE2の関与

  竹内 佐織, 肥田 裕丈, 毛利 彰宏, 吉見 陽, 森 健太郎, 山田 清文, 尾崎 紀夫, 古屋敷 智之, 成宮 周, 野田 幸裕

  (公社)日本薬学会, Mar. 2018, 日本薬学会年会要旨集, 138年会(3) (3), 84 - 84, Japanese


• Depressive-Like Behaviors Are Regulated by NOX1/NADPH Oxidase by Redox Modification of NMDA Receptor 1.

  Masakazu Ibi, Junjie Liu, Noriaki Arakawa, Shiho Kitaoka, Ai Kawaji, Ken-Ichi Matsuda, Kazumi Iwata, Misaki Matsumoto, Masato Katsuyama, Kai Zhu, Satoshi Teramukai, Tomoyuki Furuyashiki, Chihiro Yabe-Nishimura

  Involvement of reactive oxygen species (ROS) has been suggested in the development of psychiatric disorders. NOX1 is a nonphagocytic form of NADPH oxidase whose expression in the nervous system is negligible compared with other NOX isoforms. However, NOX1-derived ROS increase inflammatory pain and tolerance to opioid analgesia. To clarify the role of NOX1 in the brain, we examined depressive-like behaviors in mice deficient in Nox1 (Nox1-/Y). Depressive-like behaviors induced by chronic social defeat stress or administration of corticosterone (CORT) were significantly ameliorated in Nox1-/Y Generation of ROS was significantly elevated in the prefrontal cortex (PFC) of mice administrated with CORT, while NOX1 mRNA was upregulated only in the ventral tegmental area (VTA) among brain areas responsible for emotional behaviors. Delivery of miRNA against NOX1 to VTA restored CORT-induced depressive-like behaviors in wild-type (WT) littermates. Administration of CORT to WT, but not to Nox1-/Y, significantly reduced transcript levels of brain-derived neurotrophic factor (bdnf), with a concomitant increase in DNA methylation of the promoter regions in bdnf Delivery of miRNA against NOX1 to VTA restored the level of BDNF mRNA in WT PFC. Redox proteome analyses demonstrated that NMDA receptor 1 (NR1) was among the molecules redox regulated by NOX1. In cultured cortical neurons, hydrogen peroxide significantly suppressed NMDA-induced upregulation of BDNF transcripts in NR1-expressing cells but not in cells harboring mutant NR1 (C744A). Together, these findings suggest a key role of NOX1 in depressive-like behaviors through NR1-mediated epigenetic modification of bdnf in the mesoprefrontal projection.SIGNIFICANCE STATEMENT NADPH oxidase is a source of reactive oxygen species (ROS) that have been implicated in the pathogenesis of various neurological disorders. We presently showed the involvement of a nonphagocytic type of NADPH oxidase, NOX1, in major depressive disorders, including behavioral, biochemical, and anatomical changes in mice. The oxidation of NR1 by NOX1-derived ROS was demonstrated in prefrontal cortex (PFC), which may be causally linked to the downregulation of BDNF, promoting depressive-like behaviors. Given that NOX1 is upregulated only in VTA but not in PFC, mesocortical projections appear to play a crucial role in NOX1-dependent depressive-like behaviors. Our study is the first to present the potential molecular mechanism underlying the development of major depression through the NOX1-induced oxidation of NR1 and epigenetic modification of bdnf.

  Apr. 2017, The Journal of neuroscience : the official journal of the Society for Neuroscience, 37(15) (15), 4200 - 4212, English, International magazine

  [Refereed]

  Scientific journal


• G-CSF-induced sympathetic tone provokes fever and primes antimobilizing functions of neutrophils via PGE(2)

  Yuko Kawano, Chie Fukui, Masakazu Shinohara, Kanako Wakahashi, Shinichi Ishii, Tomohide Suzuki, Mari Sato, Noboru Asada, Hiroki Kawano, Kentaro Minagawa, Akiko Sada, Tomoyuki Furuyashiki, Satoshi Uematsu, Shizuo Akira, Toshimitsu Uede, Shuh Narumiya, Toshimitsu Matsui, Yoshio Katayama

  Feb. 2017, BLOOD, 129(5) (5), 587 - 597, English, International magazine

  [Refereed]

  Scientific journal


• Roles of Inflammation in Stress-induced Emotional Changes

  Kitaoka Shiho, Furuyashiki Tomoyuki

  Social and environmental stress evokes stress responses through endocrine, immune and autonomic nervous systems. However, how these stress responses are integrated to promote emotional changes and mental illnesses remains poorly understood. Recent studies have established critical roles of inflammation-like responses in stress-induced emotional changes, and have been studying about the involvement of endocrine, immune and autonomic nervous systems. In the periphery, stress-induced endocrine responses activate myeloid cells and increase proinflammatory cytokines, whereas stress-induced sympathetic activation increases the numbers of neutrophils and monocytes in the blood. Stress also alters the composition of gut microbiota and activates immune systems. In the brain, stress activates microglial cells and suppresses dopaminergic system in the prefrontal cortex through inflammation-related molecules. These findings suggest that multiple stress responses are converged to inflammation-like responses inside and outside the brain, thereby promoting emotional changes and mental illnesses, and have led us to propose that stress-induced inflammation-like responses are a target for therapeutic development of novel antidepressants.

  Japanese Society of Psychosomatic Medicine, 2017, Japanese Journal of Psychosomatic Medicine, 57(9) (9), 922 - 928, Japanese


• mDia and ROCK Mediate Actin-Dependent Presynaptic Remodeling Regulating Synaptic Efficacy and Anxiety

  Yuichi Deguchi, Masaya Harada, Ryota Shinohara, Michael Lazarus, Yoan Cherasse, Yoshihiro Urade, Daisuke Yamada, Masayuki Sekiguchi, Dai Watanabe, Tomoyuki Furuyashiki, Shuh Narumiya

  Nov. 2016, CELL REPORTS, 17(9) (9), 2405 - 2417, English, International magazine

  [Refereed]

  Scientific journal


• Genetic interactions among AMPK catalytic subunit Ssp2 and glycogen synthase kinases Gsk3 and Gsk31 in Schizosaccharomyces Pombe.

  Qingyun, Ma Y, Kato T, Furuyashiki T

  In Schizosaccharomyces pombe, Ssp2, an ortholog of AMP-activated protein kinase (AMPK), is critical for cell growth at restrictive temperatures and under glucose depletion as well as sexual differentiation under nitrogen depletion. To identify genes genetically related to Ssp2, we performed a genetic screening to search for the genes whose overexpression rescued the growth defects in Δssp2 cells at restrictive temperatures, and identified 35 cosmids as multicopy suppressor genes. In Southern blot analyses, 22 out of these cosmids were hybridized to an ssp2+ probe. Using nucleotide sequencing, we identified the gsk3+ gene in one of the cosmids, and the remaining 12 cosmids were hybridized to a gsk3+ probe. Overexpression of the gsk3+ gene or the gsk31+ gene, another GSK3 member, rescues defective growth of Δssp2 cells at restrictive temperatures and under glucose depletion as well as sexual differentiation under nitrogen depletion. Δgsk3Δgsk31 double knockout cells, but neither Δgsk3 nor Δgsk31 single knockout cells, phenocopy Δssp2 cells. The deletion of the gsk3+ or gsk31+ gene augments the phenotypes of Δssp2 cells. These findings suggest that Gsk3 and Gsk31 are critical and interact with Ssp2 in multiple cellular functions.

  Aug. 2016, Kobe J Med Sci, 62(3) (3), E70 - E78, English, Domestic magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• The Loss of Lam2 and Npr2-Npr3 Diminishes the Vacuolar Localization of Gtr1-Gtr2 and Disinhibits TORC1 Activity in Fission Yeast

  Ning Ma, Yan Ma, Akio Nakashima, Ushio Kikkawa, Tomoyuki Furuyashiki

  May 2016, PLOS ONE, 11(5) (5), e0156239, English, International magazine

  [Refereed]

  Scientific journal


• Tor Signaling Regulates Transcription of Amino Acid Permeases through a GATA Transcription Factor Gaf1 in Fission Yeast

  Yan Ma, Ning Ma, Qingbin Liu, Yao Qi, Ri-ichiroh Manabe, Tomoyuki Furuyashiki

  Dec. 2015, PLOS ONE, 10(12) (12), e0144677, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• The combined effect of clothianidin and environmental stress on the behavioral and reproductive function in male mice

  Tetsushi Hirano, Shogo Yanai, Takuya Omotehara, Rie Hashimoto, Yuria Umemura, Naoto Kubota, Kiichi Minami, Daichi Nagahara, Eiko Matsuo, Yoshiko Aihara, Ryota Shinohara, Tomoyuki Furuyashiki, Youhei Mantani, Toshifumi Yokoyama, Hiroshi Kitagawa, Nobuhiko Hoshi

  Oct. 2015, JOURNAL OF VETERINARY MEDICAL SCIENCE, 77(10) (10), 1207 - 1215, English, Domestic magazine

  [Refereed]

  Scientific journal


• Characterization of tamoxifen as an antifungal agent using the yeast Schizosaccharomyces pombe model organism.

  Zhang X, Fang Y, Jaiseng W, Hu L, Lu Y, Ma Y, Furuyashiki T

  Tamoxifen, a selective estrogen receptor modulator used for managing breast cancer, is known to have antifungal activity. However, its molecular mechanism remains unknown. Using the fission yeast Schizosaccharomyces pombe as a model organism, we have explored the mechanism involved in antifungal action of tamoxifen. Since tamoxifen was shown to inhibit the binding of calmodulin to calcineurin in fungi, we first examined involvement of these molecules and found that overexpression of a catalytic subunit of calcineurin and its constitutively active mutant as well as calmodulin increases tamoxifen sensitivity. Since terbinafine and azoles inhibit enzymes for ergosterol biosynthesis, Erg1 and Erg11, for their antifungal actions, we also examined involvement of these molecules. Overexpression of Erg1 and Erg11 reduced the sensitivity to terbinafine and azoles, respectively, but increased tamoxifen sensitivity, suggesting that ergosterol biosynthesis is differently related to the action of tamoxifen and those of terbinafine and azoles. To elucidate molecules involved in tamoxifen action, we performed a genome-wide screen for altered sensitivity to tamoxifen using a fission yeast gene deletion library, and identified various hypersensitive and resistant mutants to this drug. Notably, these mutants are rarely overlapped with those identified in similar genetic screens with currently used antifungals, suggesting a novel mode of antifungal action. Furthermore, tamoxifen augmented antifungal actions of terbinafine and azoles, suggesting synergetic actions between these drugs. Therefore, our findings suggest that calmodulin-calcineurin pathway and ergosterol biosynthesis are related to antifungal action of tamoxifen, and propose novel targets for antifungal development as well as combined therapy with tamoxifen for fungal diseases.

  Oct. 2015, Kobe J Med Sci, 61(2) (2), E54 - E63, English, Domestic magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Constitutive Tor2 Activity Promotes Retention of the Amino Acid Transporter Agp3 at Trans-Golgi/Endosomes in Fission Yeast

  Qingbin Liu, Yan Ma, Xin Zhou, Tomoyuki Furuyashiki

  Oct. 2015, PLOS ONE, 10(10) (10), e0139045, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Azoles activate Atf1-mediated transcription through MAP kinase pathway for antifungal effects in fission yeast

  Lingling Hu, Yue Fang, Tsutomu Hayafuji, Yan Ma, Tomoyuki Furuyashiki

  Sep. 2015, GENES TO CELLS, 20(9) (9), 695 - 705, English, International magazine

  [Refereed]

  Scientific journal


• The CCAAT/enhancer-binding protein delta/miR135a/thrombospondin 1 axis mediates PGE2-induced angiogenesis in Alzheimer's disease

  Chiung-Yuan Ko, Yu-Yi Chu, Shuh Narumiya, Jhih-Ying Chi, Tomoyuki Furuyashiki, Tomohiro Aoki, Shao-Ming Wang, Wen-Chang Chang, Ju-Ming Wang

  Mar. 2015, NEUROBIOLOGY OF AGING, 36(3) (3), 1356 - 1368, English, International magazine

  [Refereed]

  Scientific journal


• [A role of prostaglandin E2-mediated regulation of prefrontal dopaminergic activity under repeated social defeat stress].

  Tomoyuki Furuyashiki

  Feb. 2015, Seikagaku. The Journal of Japanese Biochemical Society, 87(1) (1), 122 - 4, Japanese, Domestic magazine

  Scientific journal


• Roles and actions of arachidonic acid-derived bioactive lipids in stress-related behaviors

  Tomoyuki Furuyashiki, Shiho Kitaokai

  Springer Japan, Jan. 2015, Bioactive Lipid Mediators: Current Reviews and Protocols, 315 - 328, English

  [Refereed]

  In book


• The MluI Cell Cycle Box (MCB) Motifs, but Not Damage-Responsive Elements (DREs), Are Responsible for the Transcriptional Induction of the rhp51(+) Gene in Response to DNA Replication Stress

  Wugangerile Sartagul, Xin Zhou, Yuki Yamada, Ning Ma, Katsunori Tanaka, Tomoyuki Furuyashiki, Yan Ma

  Nov. 2014, PLOS ONE, 9(11) (11), e111936, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• The possibility of prostaglandin E-2 (PGE(2)) as a common molecule associated with vulnerability to neurodevelopmental disruptions

  Hirotake Hida, Akihiro Mouri, Kentaro Mori, Tomoyuki Furuyashiki, Kiyofumi Yamada, Norio Ozaki, Shuh Narumiya, Toshitaka Nabeshima, Yukihiro Noda

  2014, JOURNAL OF PHARMACOLOGICAL SCIENCES, 124, 75P - 75P, English

  [Refereed]


• EphA4-dependent axon retraction and midline localization of Ephrin-B3 are disrupted in the spinal cord of mice lacking mDia1 and mDia3 in combination

  Yosuke Toyoda, Ryota Shinohara, Dean Thumkeo, Hiroshi Kamijo, Hiroshi Nishimaru, Hiroyuki Hioki, Takeshi Kaneko, Toshimasa Ishizaki, Tomoyuki Furuyashiki, Shuh Narumiya

  Oct. 2013, GENES TO CELLS, 18(10) (10), 873 - 885, English, International magazine

  [Refereed]

  Scientific journal


• Prostaglandin E Receptor EP1 Forms a Complex with Dopamine D1 Receptor and Directs D1-Induced cAMP Production to Adenylyl Cyclase 7 through Mobilizing G(beta gamma) Subunits in Human Embryonic Kidney 293T Cells

  Aliza T. Ehrlich, Tomoyuki Furuyashiki, Shiho Kitaoka, Akira Kakizuka, Shuh Narumiya

  Sep. 2013, MOLECULAR PHARMACOLOGY, 84(3) (3), 476 - 486, English, International magazine

  [Refereed]

  Scientific journal


• Prostaglandin E2 regulates murine hematopoietic stem/progenitor cells directly via EP4 receptor and indirectly through mesenchymal progenitor cells

  Yoshiko Matsumoto Ikushima, Fumio Arai, Kentaro Hosokawa, Hirofumi Toyama, Keiyo Takubo, Tomoyuki Furuyashiki, Shuh Narumiya, Toshio Suda

  American Society of Hematology, 2013, Blood, 121(11) (11), 1995 - 2007, English, International magazine

  [Refereed]

  Scientific journal


• Involvement of prostaglandin E2 in behavioral abnormalities induced by neonatal immune activation

  Hirotake Hida, Akihiro Mouri, Tomoyuki Furuyashiki, Kiyofumi Yamada, Norio Ozaki, Shuh Narumiya, Toshitaka Nabeshima, Yukihiro Noda

  2013, JOURNAL OF PHARMACOLOGICAL SCIENCES, 121, 123P - 123P, English

  [Refereed]


• Roles of Dopamine and Inflammation-Related Molecules in Behavioral Alterations Caused by Repeated Stress

  Tomoyuki Furuyashiki

  Oct. 2012, JOURNAL OF PHARMACOLOGICAL SCIENCES, 120(2) (2), 63 - 69, English, Domestic magazine

  [Refereed][Invited]

  Scientific journal


• Orally administered rubiscolin-6, a delta opioid peptide derived from Rubisco, stimulates food intake via leptomeningeal lipocallin-type prostaglandin D synthase in mice

  Kentaro Kaneko, Michael Lazarus, Chihiro Miyamoto, Yo Oishi, Nanae Nagata, Shuzhang Yang, Masaaki Yoshikawa, Kosuke Aritake, Tomoyuki Furuyashiki, Shuh Narumiya, Yoshihiro Urade, Kousaku Ohinata

  Aug. 2012, MOLECULAR NUTRITION & FOOD RESEARCH, 56(8) (8), 1315 - 1323, English, International magazine

  [Refereed]

  Scientific journal


• Roles of altered striatal function in major depression

  Tomoyuki Furuyashiki, Yuichi Deguchi

  Aug. 2012, Brain and Nerve, 64(8) (8), 919 - 926, Japanese, Domestic magazine

  [Refereed]

  Scientific journal


• [Role of prostaglandin signaling in stress and its implication in pharmaceutical development of antidepressants].

  Kohei Tanaka, Tomoyuki Furuyashiki

  Apr. 2012, Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 139(4) (4), 152 - 6, Japanese, Domestic magazine

  Scientific journal


• [Environmental factors that influence the pathophysiology of mental disorders in various life stages and the design of molecular- targeting drugs for these disorders].

  Tomoyuki Furuyashiki, Taku Yamaguchi

  Apr. 2012, Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 139(4) (4), 141 - 141, Japanese, Domestic magazine

  Scientific journal


• Role of PGE-type receptor 4 in auditory function and noise-induced hearing loss in mice

  Kiyomi Hamaguchi, Norio Yamamoto, Takayuki Nakagawa, Tomoyuki Furuyashiki, Shuh Narumiya, Juichi Ito

  Mar. 2012, NEUROPHARMACOLOGY, 62(4) (4), 1841 - 1847, English, International magazine

  [Refereed]

  Scientific journal


• Prostaglandin E-2-Mediated Attenuation of Mesocortical Dopaminergic Pathway Is Critical for Susceptibility to Repeated Social Defeat Stress in Mice

  Kohei Tanaka, Tomoyuki Furuyashiki, Shiho Kitaoka, Yuta Senzai, Yuki Imoto, Eri Segi-Nishida, Yuichi Deguchi, Richard M. Breyer, Matthew D. Breyer, Shuh Narumiya

  Mar. 2012, JOURNAL OF NEUROSCIENCE, 32(12) (12), 4319 - 4329, English, International magazine

  [Refereed]

  Scientific journal


• A role for mDia, a Rho-regulated actin nucleator, in tangential migration of interneuron precursors

  Ryota Shinohara, Dean Thumkeo, Hiroshi Kamijo, Naoko Kaneko, Kazunobu Sawamoto, Keisuke Watanabe, Hirohide Takebayashi, Hiroshi Kiyonari, Toshimasa Ishizaki, Tomoyuki Furuyashiki, Shuh Narumiya

  Mar. 2012, NATURE NEUROSCIENCE, 15(3) (3), 373 - U193, English, International magazine

  [Refereed]

  Scientific journal


• Deficiency of mDia, an Actin Nucleator, Disrupts Integrity of Neuroepithelium and Causes Periventricular Dysplasia

  Dean Thumkeo, Ryota Shinohara, Keisuke Watanabe, Hirohide Takebayashi, Yosuke Toyoda, Kiyoshi Tohyama, Toshimasa Ishizaki, Tomoyuki Furuyashiki, Shuh Narumiya

  Sep. 2011, PLOS ONE, 6(9) (9), e25465, English, International magazine

  [Refereed]

  Scientific journal


• PGE2はEP1/EP4受容体を介して抗不安作用を示す

  宮本 知京, 鈴木 千尋, 古屋敷 智之, 成宮 周, 大日向 耕作

  (公社)日本生化学会, Sep. 2011, 日本生化学会大会プログラム・講演要旨集, 84回, 3T8p - 7, Japanese


• Rho依存的アクチン重合因子mDiaはephrinによる軸索成長円錐の退縮に重要である(mDia, a Rho effector and actin nucleator, is critical for growth cone retraction in ephrin-induced axonal repulsion)

  豊田 洋輔, 篠原 亮太, タムケオ・ディーン, 上條 博史, 日置 寛之, 金子 武嗣, 石崎 敏理, 古屋敷 智之, 成宮 周

  (公社)日本生化学会, Sep. 2011, 日本生化学会大会プログラム・講演要旨集, 84回, 3P - 0588, Japanese


• Thromboxane receptor activation enhances striatal dopamine release, leading to suppression of GABAergic transmission and enhanced sugar intake

  Tomoyuki Mitsumori, Tomoyuki Furuyashiki, Toshihiko Momiyama, Akinori Nishi, Takahide Shuto, Takashi Hayakawa, Fumitaka Ushikubi, Shiho Kitaoka, Tomohiro Aoki, Haruhisa Inoue, Toshiyuki Matsuoka, Shuh Narumiya

  Aug. 2011, EUROPEAN JOURNAL OF NEUROSCIENCE, 34(4) (4), 594 - 604, English, International magazine

  [Refereed]

  Scientific journal


• PGE(2)-EP2 signalling in endothelium is activated by haemodynamic stress and induces cerebral aneurysm through an amplifying loop via NF-kappa B

  T. Aoki, M. Nishimura, T. Matsuoka, K. Yamamoto, T. Furuyashiki, H. Kataoka, S. Kitaoka, R. Ishibashi, A. Ishibazawa, S. Miyamoto, R. Morishita, J. Ando, N. Hashimoto, K. Nozaki, S. Narumiya

  Jul. 2011, BRITISH JOURNAL OF PHARMACOLOGY, 163(6) (6), 1237 - 1249, English

  [Refereed]

  Scientific journal


• Central PGE(2) exhibits anxiolytic-like activity via EP1 and EP4 receptors in a manner dependent on serotonin 5-HT1A, dopamine D-1 and GABA(A) receptors

  Chihiro Suzuki, Chihiro Miyamoto, Tomoyuki Furuyashiki, Shuh Narumiya, Kousaku Ohinata

  Jul. 2011, FEBS LETTERS, 585(14) (14), 2357 - 2362, English, International magazine

  [Refereed]

  Scientific journal


• Fever, inflammation, pain and beyond: prostanoid receptor research during these 25 years

  Shuh Narumiya, Tomoyuki Furuyashiki

  Mar. 2011, FASEB JOURNAL, 25(3) (3), 813 - 818, English, International magazine

  [Refereed][Invited]

  Scientific journal


• Stress responses: the contribution of prostaglandin E-2 and its receptors

  Tomoyuki Furuyashiki, Shuh Narumiya

  Mar. 2011, NATURE REVIEWS ENDOCRINOLOGY, 7(3) (3), 163 - 175, English, International magazine

  [Refereed][Invited]

  Scientific journal


• Prostaglandin E receptor EP1 enhances GABA-mediated inhibition of dopaminergic neurons in the substantia nigra pars compacta and regulates dopamine level in the dorsal striatum

  Yasuhiro Tanaka, Tomoyuki Furuyashiki, Toshihiko Momiyama, Hisaaki Namba, Akira Mizoguchi, Tomoyuki Mitsumori, Tetsuro Kayahara, Hitoshi Shichi, Kazushi Kimura, Toshiyuki Matsuoka, Hiroyuki Nawa, Shuh Narumiya

  Dec. 2009, EUROPEAN JOURNAL OF NEUROSCIENCE, 30(12) (12), 2338 - 2346, English, International magazine

  [Refereed]

  Scientific journal


• Central control of fever and female body temperature by RANKL/RANK

  Reiko Hanada, Andreas Leibbrandt, Toshikatsu Hanada, Shiho Kitaoka, Tomoyuki Furuyashiki, Hiroaki Fujihara, Jean Trichereau, Magdalena Paolino, Fatimunnisa Qadri, Ralph Plehm, Steffen Klaere, Vukoslav Komnenovic, Hiromitsu Mimata, Hironobu Yoshimatsu, Naoyuki Takahashi, Arndt von Haeseler, Michael Bader, Sara Sebnem Kilic, Yoichi Ueta, Christian Pifl, Shuh Narumiya, Josef M. Penninger

  Nov. 2009, NATURE, 462(7272) (7272), 505 - 509, English, International magazine

  [Refereed]

  Scientific journal


• Roles of prostaglandin E receptors in stress responses

  Tomoyuki Furuyashiki, Shuh Narumiya

  Feb. 2009, CURRENT OPINION IN PHARMACOLOGY, 9(1) (1), 31 - 38, English, International magazine

  [Refereed]

  Scientific journal


• Rat orbitofrontal cortex separately encodes response and outcome information during performance of goal-directed behavior

  Tomoyuki Furuyashiki, Peter C. Holland, Michela Gallagher

  May 2008, JOURNAL OF NEUROSCIENCE, 28(19) (19), 5127 - 5138, English, International magazine

  [Refereed]

  Scientific journal


• Facilitation of Th1-mediated immune response by prostaglandin E receptor EP1

  Miyako Nagamachi, Daiji Sakata, Kenji Kabashima, Tomoyuki Furuyashiki, Takahiko Murata, Eri Segi-Nishida, Kitipong Soontrapa, Toshiyuki Matsuoka, Yoshiki Miyachi, Shuh Narumiya

  Nov. 2007, JOURNAL OF EXPERIMENTAL MEDICINE, 204(12) (12), 2865 - 2874, English, International magazine

  [Refereed]

  Scientific journal


• Prostaglandin E-2 acts on EP1 receptor and amplifies both dopamine D-1 and D-2 receptor signaling in the striatum

  Shiho Kitaoka, Tomoyuki Furuyashiki, Akinori Nishi, Takahide Shuto, Sho Koyasu, Toshiyuki Matsuoka, Masayuki Miyasaka, Paul Greengard, Shuh Narumiya

  Nov. 2007, JOURNAL OF NEUROSCIENCE, 27(47) (47), 12900 - 12907, English, International magazine

  [Refereed]

  Scientific journal


• Neural encoding in the orbitofrontal cortex related to goal-directed behavior

  Tomoyuki Furuyashiki, Michela Gallagher

  2007, LINKING AFFECT TO ACTION: CRITICAL CONTRIBUTIONS OF THE ORBITOFRONTAL CORTEX, 1121, 193 - 215, English, International magazine

  [Refereed]

  Scientific journal


• Molecular identification and characterization of a family of kinases with homology to Ca2+/calmodulin-dependent protein kinases I/IV

  Shogo Ohmae, Sayaka Takemoto-Kimura, Michiko Okamura, Aki Adachi-Morishima, Mio Nonaka, Toshimitsu Fuse, Satoshi Kida, Masahiro Tanji, Tomoyuki Furuyashiki, Yoshiki Arakawa, Shuh Narumiya, Hiroyuki Okuno, Haruhiko Bito

  Jul. 2006, JOURNAL OF BIOLOGICAL CHEMISTRY, 281(29) (29), 20427 - 20439, English, International magazine

  [Refereed]

  Scientific journal


• Prostaglandin E receptor EP1 controls impulsive behavior under stress

  Y Matsuoka, T Furuyashiki, K Yamada, T Nagai, H Bito, Y Tanaka, S Kitaoka, F Ushikubi, T Nabeshima, S Narumiya

  Nov. 2005, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 102(44) (44), 16066 - 16071, English, International magazine

  [Refereed]

  Scientific journal


• Enhanced cocaine responsiveness and impaired motor coordination in metabotropic glutamate receptor subtype 2 knockout mice

  Y Morishima, T Miyakawa, T Furuyashiki, Y Tanaka, H Mizuma, S Nakanishi

  Mar. 2005, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 102(11) (11), 4170 - 4175, English, International magazine

  [Refereed]

  Scientific journal


• Molecular cloning and characterization of CLICK-III/CaMKI gamma, a novel membrane-anchored neuronal Ca2+/calmodulin-dependent protein kinase (CaMK)

  S Takemoto-Kimura, H Terai, M Takamoto, S Ohmae, S Kikumura, E Segi, Y Arakawa, T Furuyashiki, S Narumiya, H Bito

  May 2003, JOURNAL OF BIOLOGICAL CHEMISTRY, 278(20) (20), 18597 - 18605, English, International magazine

  [Refereed]

  Scientific journal


• Control of axon elongation via an SDF-1 alpha/Rho/mDia pathway in cultured cerebellar granule neurons

  Y Arakawa, H Bito, T Furuyashiki, T Tsuji, S Takemoto-Kimura, K Kimura, K Nozaki, N Hashimoto, S Narumiya

  Apr. 2003, JOURNAL OF CELL BIOLOGY, 161(2) (2), 381 - 391, English, International magazine

  [Refereed]

  Scientific journal


• Impaired adrenocorticotropic hormone response to bacterial endotoxin in mice deficient in prostaglandin E receptor EP1 and EP3 subtypes

  Y Matsuoka, T Furuyashiki, H Bito, F Ushikubi, Y Tanaka, T Kobayashi, S Muro, N Satoh, T Kayahara, M Higashi, A Mizoguchi, H Shichi, Y Fukuda, K Nakao, S Narumiya

  Apr. 2003, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 100(7) (7), 4132 - 4137, English, International magazine

  [Refereed]

  Scientific journal


• Multiple spatiotemporal modes of actin reorganization by NMDA receptors and voltage-gated Ca2+ channels

  T Furuyashiki, Y Arakawa, S Takemoto-Kimura, H Bito, S Narumiya

  Oct. 2002, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 99(22) (22), 14458 - 14463, English, International magazine

  [Refereed]

  Scientific journal


• ROCK and mDia1 antagonize in Rho-dependent Rac activation in Swiss 3T3 fibroblasts

  T Tsuji, T Ishizaki, M Okamoto, C Higashida, K Kimura, T Furuyashiki, Y Arakawa, RB Birge, T Nakamoto, H Hirai, S Narumiya

  May 2002, JOURNAL OF CELL BIOLOGY, 157(5) (5), 819 - 830, English, International magazine

  [Refereed]

  Scientific journal


• Coordination of microtubules and the actin cytoskeleton by the Rho effector mDia1

  T Ishizaki, Y Morishima, M Okamoto, T Furuyashiki, T Kato, S Narumiya

  Jan. 2001, NATURE CELL BIOLOGY, 3(1) (1), 8 - 14, English

  [Refereed]

  Scientific journal


• A critical role for a Rho-associated kinase, p160ROCK, in determining axon outgrowth in mammalian CNS neurons

  H Bito, T Furuyashiki, H Ishihara, Y Shibasaki, K Ohashi, K Mizuno, M Maekawa, T Ishizaki, S Narumiya

  May 2000, NEURON, 26(2) (2), 431 - 441, English

  [Refereed]

  Scientific journal


• Citron, a Rho target that affects contractility during cytokinesis

  P Madaule, T Furuyashiki, M Eda, H Bito, T Ishizaki, S Narumiya

  Apr. 2000, MICROSCOPY RESEARCH AND TECHNIQUE, 49(2) (2), 123 - 126, English

  [Refereed]

  Scientific journal


• Citron, a Rho-target, interacts with PSD-95/SAP-90 at glutamatergic synapses in the thalamus

  T Furuyashiki, K Fujisawa, A Fujita, P Madaule, S Uchino, M Mishina, H Bito, S Narumiya

  Jan. 1999, JOURNAL OF NEUROSCIENCE, 19(1) (1), 109 - 118, English

  [Refereed]

  Scientific journal


• Rho標的分子,Citronは視床のグルタミン酸性シナプスでPSD-95と結合する

  古屋敷 智之, 藤澤 和子, 藤田 明子, Madaule Pascal, 喜久村 祥子, 内野 茂夫, 三品 昌美, 尾藤 晴彦, 成宮 周

  日本神経化学会, Sep. 1998, 神経化学, 37(3) (3), 410 - 410, Japanese


• Rhotekin, a new putative target for Rho bearing homology to a serine/threonine kinase, PKN, and rhophilin in the Rho-binding domain

  T Reid, T Furayashiki, T Ishizaki, G Watanabe, N Watanabe, K Fujisawa, N Morii, P Madaule, S Narumiya

  Jun. 1996, JOURNAL OF BIOLOGICAL CHEMISTRY, 271(23) (23), 13556 - 13560, English

  [Refereed]

  Scientific journal


• A novel partner for the GTP-bound forms of rho and rac

  P Madaule, T Furuyashiki, T Reid, T Ishizaki, G Watanabe, N Morii, S Narumiya

  Dec. 1995, FEBS LETTERS, 377(2) (2), 243 - 248, English

  [Refereed]

  Scientific journal

• 脳内炎症は骨格筋のC/EBP経路を介してストレス性筋萎縮を促進する

  内山 奏, 平田 悠, 野村 和弘, Wijaya Hendy, 谷口 将之, 北岡 志保, 古屋敷 智之, 小川 渉

  日本臨床分子医学会, Apr. 2023, 日本臨床分子医学会学術総会プログラム・抄録集, 58回, 56 - 56, Japanese


• 脳内炎症は骨格筋のC/EBP経路を介してストレス性筋萎縮を促進する

  内山 奏, 平田 悠, 野村 和弘, Wijaya Hendy, 谷口 将之, 北岡 志保, 古屋敷 智之, 小川 渉

  (一社)日本糖尿病学会, Apr. 2023, 糖尿病, 66(Suppl.1) (Suppl.1), S - 189, Japanese


• Social stress induces microglial contact with synapses, contributing to the release of heparan sulfate from synaptic proteoglycans in mice

  NAGAI Midori, NAGAI Hirotaka, NUMA Chisato, NADANAKA Satomi, KAWASHIMA Yusuke, OHNO Nobuhiko, KITAGAWA Hiroshi, FURUYASHIKI Tomoyuki

  2023, 日本薬理学会年会要旨集(Web), 97th


• 脳内炎症は骨格筋のC/EBP経路を介してストレス性筋萎縮を促進する

  内山 奏, 平田 悠, 野村 和弘, Hendy Wijaya, 谷口 将之, 北岡 志保, 古屋敷 智之, 小川 渉

  (一社)日本肥満学会, Nov. 2022, 肥満研究, 28(Suppl.) (Suppl.), 322 - 322, Japanese


• マウスの社会ストレスは前頭前皮質錐体神経細胞の樹状突起消失に先行して細胞内変性を誘導する

  沼知里, 永井裕崇, 永井碧, 山下朋美, 川島祐介, 大野伸彦, 片岡洋祐, 片岡洋祐, 三森(清末)優子, 加藤太朗, 古屋敷智之

  2022, 日本神経化学会大会抄録集(Web), 65th


• Analysis of synaptic structural changes induced by chronic social stress and their molecular mechanisms

  Nagai Hirotaka, Nagai Midori, Numa Chisato, Ota Kohei, Yamashita Tomomi, Kawashima Yusuke, Ohno Nobuhiko, Kataoka Yosky, Shimma Shuuichi, Mimori-Kiyosue Yuko, Kato Taro, Soga Tomoyoshi, Furuyashiki Tomoyuki

  Excessive or chronic social stress induces emotional and cognitive disturbances and precipitates mental illness. Altered neuronal morphology and functions in the medial prefrontal cortex (mPFC) underlie these behavioral abnormalities. However, its subcellular mechanisms remain elusive. Here we examined ultrastructural and multi-omics changes in the mPFC after social stress in mice. Social stress caused the loss of dendritic branches with morphological alterations of subcellular mitochondria and induced synaptic shrinkage selectively at the synapses with mitochondria. Multi-omics and functional analyses revealed that social stress deteriorated mitochondrial functions with altered mitochondrial proteome at synapses and dysregulated central metabolic pathways in the mPFC. Molecular biological and pharmacological manipulation targeting central metabolism and mitochondria attenuated the synaptic shrinkage and depression-related behaviors. These findings demonstrate that chronic social stress alters the central metabolism at mPFC synapses, leading to neuronal pathology and depression-related behaviors.

  Japanese Pharmacological Society, 2022, Proceedings for Annual Meeting of The Japanese Pharmacological Society, 96, 3-B-O06-4, Japanese


• Analysis of aging-induced neural dysfunctions and their biological basis

  Rui Yamada, Nagai Hirotaka, Numa Chisato, Horikawa Io, Nagai Midori, Kawashima Yusuke, Furuyashiki Tomoyuki

  Aging causes cognitive and motivational declines, but the biological basis remains elusive. Here we analyzed distinct behavioral effects of aging in C57BL6N (B6N) and C57BL/6J (B6J) strains. In this study, mice first learned a visual discrimination task to obtain food rewards by responding to the correct one of two visual stimuli. Then, they learned a response direction task of responding to either left or right for food rewards. Attentional set-shifting, behavioral flexibility between the tasks, is known to depend on working memory. Aged B6N mice showed motivational declines in both tasks. By contrast, task motivation was intact in aged B6J mice, but some of them showed a deficit in attentional set-shifting. We also analyzed synaptic proteomes in the medial prefrontal cortex, a brain region crucial for attentional set-shifting. Young and aged B6J mice showed differential expression of many synaptic proteins, some of which increased only in a subset of the aged mice with attentional set-shifting intact. These findings suggest that different biological mechanisms related to genetic and synaptic factors underlie motivation and cognitive declines with aging.

  Japanese Pharmacological Society, 2022, Proceedings for Annual Meeting of The Japanese Pharmacological Society, 95, 1-SS-43, Japanese


• Stress history monitoring based on mass spectrometry imaging in hair strand

  植木瞭生, 永井裕崇, 古屋敷智之, 福崎英一郎, 福崎英一郎, 福崎英一郎, 新間秀一, 新間秀一, 新間秀一

  (公社)日本生物工学会, 2021, 日本生物工学会大会講演要旨集, 73rd, 148 - 148, Japanese


• Chronic Stress-Induced Epigenetic Changes of Microglia

  Masayuki Taniguchi, Kazutoshi Matsushita, Mitsutaka Kadota, Shigehiro Kuraku, Tomoyuki Furuyashiki

  Dec. 2020, NEUROPSYCHOPHARMACOLOGY, 45(SUPPL 1) (SUPPL 1), 107 - 108, English

  Summary international conference


• Roles and Mechanisms of Neuroinflammation in Stress and Depression

  Ayaka Tomohiro, Shinya Ukeshima, Shiho Kitaoka, Xiang Nie, Keyue Liu, Hidenori Wake, Kiyoshi Teshigawara, Masahiro Nishibori, Tomoyuki Furuyashiki

  Dec. 2019, NEUROPSYCHOPHARMACOLOGY, 44(SUPPL 1) (SUPPL 1), 120 - 121, English

  Summary international conference


• 神経発達脆弱性因子による成体期の精神機能への影響:PGE₂の関与

  竹内佐織, 肥田裕丈, 毛利彰宏, 吉見陽, 森健太郎, 山田清文, 尾崎紀夫, 古屋敷智之, 成宮周, 野田幸裕

  2018, 日本薬学会年会要旨集(CD-ROM), 138th


• Elevated p62 and attenuated autophagy cause GABA receptor downregulation and underlie the pathophysiology of neuropsychiatric manifestation

  Akiko Sumitomo, Keisho Ueta, Kouta Horike, Shiho Kitaoka, Tomoyuki Furuyashiki, Takatoshi Hikida, Takeshi Sakurai, Akira Sawa, Toshifumi Tomoda, Shuh Narumiya

  Mar. 2017, JOURNAL OF PHARMACOLOGICAL SCIENCES, 133(3) (3), S221 - S221, English

  Summary international conference


• Innate immune molecules activate microglia in mPFC to induce neuronal and emotional changes in mice.

  Shiho Kitaoka, Tomoyuki Furuyashiki, Yuki Imoto, Kazuki Nakayama, Shuh Narumiya, Xiang Nie, Atsubumi Ogawa, Eri Segi-Nishida, Kohei Tanaka, Ayaka Tomohiro

  Jun. 2016, INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 19, 122 - 122, English

  Summary international conference


• Dopamine D1 receptor in the medial prefrontal cortex mediates behavioral resilience under stress in mice

  Ryota Shinohara, Yuichi Deguchi, Aliza Ehrlich, Tomoyuki Furuyashiki, Shiho Kitaoka, Shuh Narumiya, Atsubumi Ogawa, Akira Sawa, Masayuki Taniguchi, Kentarou Yokogawa

  Jun. 2016, INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 19, 96 - 96, English

  Summary international conference


• Repeated stress activates mPFC microglia through innate immune molecules for neuronal and emotional changes in mice

  Shiho Kitaoka, Xiang Nie, Kohei Tanaka, Atsubumi Ogawa, Ayaka Tomohiro, Kazuki Nakayama, Yuki Imoto, Eri Segi-Nishida, Shuh Narumiya, Tomoyuki Furuyashiki

  Mar. 2016, JOURNAL OF PHARMACOLOGICAL SCIENCES, 130(3) (3), S122 - S122, English

  Summary international conference


• 周産期における免疫応答異常による精神機能への影響 : Prostaglandin E₂ (PGE₂)-EP1受容体シグナル伝達系の関与

  野田 幸裕, 肥田 裕丈, 毛利 彰宏, 長谷川 章, 成宮 周, 古屋敷 智之, 尾崎 紀夫, 鍋島 俊隆

  名城大学総合研究所, 2016, 名城大学総合研究所紀要, (21) (21), 93 - 96, Japanese


• Roles of dopaminergic systems and inflammation-related molecules derived from microglia in stress-induced behavioral changes

  Ryota Shinohara, Shiho Kitaoka, Tomoyuki Furuyashiki

  2016, PAIN RESEARCH, 31(1) (1), 1 - 8, Japanese

  Book review


• A role for mDia, a Rho-regulated actin nucleator, in regulating morphology of presynaptic terminals and increased anxiety-like behavior induced by social isolation stress in mice

  Yuichi Deguchi, Masaya Harada, Ryota Shinohara, Michael Lazarus, Yoan Cherasse, Yoshihiro Urade, Dai Watanabe, Tomoyuki Furuyashiki, Shuh Narumiya

  Jul. 2015, JOURNAL OF PHARMACOLOGICAL SCIENCES, 128(3) (3), S92 - S92, English

  Summary international conference


• The prostaglandin E-2 induces neuronal and behavioral impairments like psychiatric disorders

  Hirotake Hida, Akihiro Mouri, Kentaro Mori, Tomoyuki Furuyashiki, Kiyofumi Yamada, Norio Ozaki, Shuh Narumiya, Toshitaka Nabeshima, Yukihiro Noda

  Jul. 2015, JOURNAL OF PHARMACOLOGICAL SCIENCES, 128(3) (3), S91 - S91, English

  Summary international conference


• The role of innate immune molecules in behavioral changes induced by repeated social defeat stress in mice

  Shiho Kitaoka, Xiang Nie, Kohei Tanaka, Atsubumi Ogawa, Yuki Imoto, Eri Segi-Nishida, Shuh Narumiya, Tomoyuki Furuyashiki

  Jul. 2015, JOURNAL OF PHARMACOLOGICAL SCIENCES, 128(3) (3), S43 - S43, English

  Summary international conference


• TOR signaling pathway regulates transcription of Isp5, an amino acid permease, through GATA transcription factor Gaf1 in fission yeast

  Yan Ma, Ning Ma, Qingbin Liu, Yao Qi, Tomoyuki Furuyashiki

  Jul. 2015, JOURNAL OF PHARMACOLOGICAL SCIENCES, 128(3) (3), S140 - S140, English

  Summary international conference


• A role for dopamine D1 receptor in the medial prefrontal cortex in stress-induced emotional changes

  Ryota Shinohara, Masayuki Taniguchi, Aliza Ehrlich, Kentaro Yokogawa, Shuh Narumiya, Tomoyuki Furuyashiki

  Jul. 2015, JOURNAL OF PHARMACOLOGICAL SCIENCES, 128(3) (3), S227 - S227, English

  Summary international conference


• 新生仔期マウスへのプロスタグランジンE2暴露が若年期や成体期における精神行動に及ぼす影響

  肥田 裕丈, 森 健太郎, 毛利 彰宏, 山田 清文, 尾崎 紀夫, 古屋敷 智之, 成宮 周

  日本臨床精神神経薬理学会・日本神経精神薬理学会, Nov. 2014, 日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集, 24回・44回, 206 - 206, Japanese


• Roles of inflammation-related molecules in emotional changes induced by repeated stress

  Shiho Kitaoka, Tomoyuki Furuyashiki

  Aug. 2014, JAPANESE JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 34(4) (4), 109 - 115, Japanese, Domestic magazine


• A role for mDia, a Rho-regulated actin nucleator, in elevated anxiety induced by social isolation stress in mice

  Yuichi Deguchi, Masaya Harada, Ryota Shinohara, Michael Lazarus, Yoan Cherasse, Yoshihiro Urade, Tomoyuki Furuyashiki, Shuh Narumiya

  2014, JOURNAL OF PHARMACOLOGICAL SCIENCES, 124, 98P - 98P, English

  Summary international conference


• The innate immune signaling plays an essential role in stress-induced emotional changes

  Shiho Kitaoka, Nie Xiang, Kohei Tanaka, Atsubumi Ogawa, Yuki Imoto, Eri Segi-Nichida, Shuh Narumiya, Tomoyuki Furuyashiki

  2014, JOURNAL OF PHARMACOLOGICAL SCIENCES, 124, 215P - 215P, English

  Summary international conference


• Functional changes of the medial prefrontal cortex induced by repeated social defeat stress in mice

  Ryota Shinohara, Aliza Ehrlich, Kentaro Yokogawa, Shuh Narumiya, Tomoyuki Furuyashiki

  2014, JOURNAL OF PHARMACOLOGICAL SCIENCES, 124, 217P - 217P, English

  Summary international conference


• A Role for Innate Immune Signaling in Microglia in Behavioral Changes Induced by Repeated Social Defeat Stress in Mice

  Xiang Nie, Shiho Kitaoka, Kohei Tanaka, Eri Segi-Nishida, Yuki Imoto, Atsubumi Ogawa, Shuh Narumiya, Tomoyuki Furuyashiki

  Dec. 2013, NEUROPSYCHOPHARMACOLOGY, 38, S548 - S549, English

  Summary international conference


• Metabolomic investigation in TP receptor deficient mice

  E. Mudersbach, C. Prehn, D. Atzler, R. Benndorf, R. H. Boeger, R. Nuesing, T. Furuyashiki, S. Narumiya, E. Schwedhelm, J. Adamski

  Feb. 2013, NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 386, S57 - S57, English

  Summary international conference


• A role for inflammation-related molecules in behavioral depression induced by repeated stress in mice

  Tomoyuki Furuyashiki, Shiho Kitaoka, Kohei Tanaka, Yuta Senzai, Xiang Nie, Shuh Narumiya

  2013, JOURNAL OF PHARMACOLOGICAL SCIENCES, 121, 80P - 80P, English

  Summary international conference


• Prostaglandin E receptor EP1 forms a complex with dopamine D1 receptor, regulates ligand binding of D1 receptors, and stimulates D1-induced cAMP production through G beta(Y) in HEK293T cells

  Aliza Ehrlich, Shiho Kitaoka, Tomoyuki Furuyashiki, Shuh Narumiya

  2013, JOURNAL OF PHARMACOLOGICAL SCIENCES, 121, 64P - 64P, English

  Summary international conference


• ストレスとミクログリア

  古屋敷 智之

  01 Dec. 2012, 日本薬理學雜誌 = Folia pharmacologica Japonica, 140(6) (6), 307 - 307, Japanese


• 新生仔期の免疫異常により惹起される行動障害におけるプロスタグランジンE2の関与

  肥田 裕丈, 毛利 彰宏, 古屋敷 智之, 鈴木 守人, 鵜飼 麻由, 谷口 将之, 山田 清文, 尾崎 紀夫, 成宮 周, 鍋島 俊隆, 野田 幸裕

  日本臨床精神神経薬理学会・日本神経精神薬理学会, Oct. 2012, 日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集, 22回・42回, 167 - 167, Japanese


• ストレスにおける中脳ドパミン系の役割

  古屋敷 智之

  01 Oct. 2012, 日本薬理學雜誌 = Folia pharmacologica Japonica, 140(4) (4), 185 - 185, Japanese


• 注目の遺伝子(第18回)ストレス関連分子プロスタグランジンE₂

  古屋敷 智之, 成宮 周

  先端医学社, Jul. 2012, 分子精神医学, 12(3) (3), 215 - 217, Japanese


• Attenuation of the mesocortical dopaminergic pathway and concomitant microglial activation in repeated social defeat stress in mice: Possible link via prostaglandin signaling

  Tomoyuki Furuyashiki, Kohei Tanaka, Shiho Kitaoka, Yuki Imoto, Eri Segi-Nishida, Yuta Senzai, Yuichi Deguchi, Shuh Narumiya

  2012, JOURNAL OF PHARMACOLOGICAL SCIENCES, 118, 29P - 29P, English

  Summary international conference


• Roles of prostaglandin E-2-mediated dopaminergic regulation for emotional behavior under stress

  Tomoyuki Furuyashiki

  2012, JOURNAL OF PHARMACOLOGICAL SCIENCES, 118, 8P - 8P, English

  Summary international conference


• Prostaglandin E receptor EP1 exerts a Ca2+-independent action in augmenting dopamine D1 receptor signaling via the C terminal domain of EP1

  Aliza Ehrlich, Tomoyuki Furuyashiki, Shiho Kitaoka, Shuh Narumiya

  2011, JOURNAL OF PHARMACOLOGICAL SCIENCES, 115, 256P - 256P, English

  Summary international conference


• Prostaglandin E-2-EP2 signaling mediates chronic inflammation in cerebral aneurysm formation via NF-kappa B

  Tomohiro Aoki, Tomoyuki Furuyashiki, Kimiko Yamamoto, Susumu Miyamoto, Kazuhiko Nozaki, Shuh Narumiya

  2011, JOURNAL OF PHARMACOLOGICAL SCIENCES, 115, 175P - 175P, English

  Summary international conference


• Prostaglandin E receptor EP1 is critical for social withdrawal and the plasticity of dopaminergic neurons after repeated social defeat

  Kohei Tanaka, Shiho Kitaoka, Yuta Senzai, Tomoyuki Furuyashiki, Shuh Narumiya

  2011, NEUROSCIENCE RESEARCH, 71, E167 - E167, English

  Summary international conference


• Prostaglandin E receptor EP1 is critical for social withdrawal and the plasticity of dopaminergic neurons after repeated social defeat in mice

  Kohei Tanaka, Shiho Kitaoka, Yuta Senzai, Tomoyuki Furuyashiki, Shuh Narumiya

  2011, JOURNAL OF PHARMACOLOGICAL SCIENCES, 115, 252P - 252P, English

  Summary international conference


• Roles of mDia isoforms, a Rho effector, in neuroblast migration

  Ryota Shinohara, Dean Thumkeo, Hiroshi Kamijo, Naoko Kaneko, Kazunobu Sawamoto, Keisuke Watanabe, Hirohide Takebayashi, Toshimasa Ishizaki, Tomoyuki Furuyashiki, Shuh Narumiya

  2011, JOURNAL OF PHARMACOLOGICAL SCIENCES, 115, 133P - 133P, English

  Summary international conference


• Roles of prostaglandin E-2 in emotional behavior under acute and chronic stress

  Tomoyuki Furuyashiki, Kohei Tanaka, Shiho Kitaoka, Yuta Senzai, Shuh Narumiya

  2011, JOURNAL OF PHARMACOLOGICAL SCIENCES, 115, 47P - 47P, English

  Summary international conference


• mDia, an actin nucleator and a Rho effector, is critical for tangential migration of cortical and olfactory bulb inhibitory interneuron precursors

  Ryota Shinohara, Dean Thumkeo, Hiroshi Kamijo, Naoko Kaneko, Kazunobu Sawamoto, Keisuke Watanabe, Hirohide Takebayashi, Hiroshi Kiyonari, Toshimasa Ishizaki, Tomoyuki Furuyashiki, Shuh Narumiya

  2011, NEUROSCIENCE RESEARCH, 71, E130 - E130, English

  Summary international conference


• Prostaglandin E-2-mediated desensitization of mesocortical dopamine neurons is critical for susceptibility to repeated social defeat stress

  Tomoyuki Furuyashiki, Kohei Tanaka, Shiho Kitaoka, Yuta Senzai, Shuh Narumiya

  2011, NEUROSCIENCE RESEARCH, 71, E52 - E52, English

  Summary international conference


• ドパミン系と興奮性シナプス可塑性におけるプロスタグランジンE2とその受容体の役割 (シナプスをめぐるシグナリンク)

  古屋敷 智之, 成宮 周

  金原一郎記念医学医療振興財団, Sep. 2010, 生体の科学, 61(5) (5), 474 - 477, Japanese


• Central control of body temperature by the osteoclast differentiation factors RANK/RANK

  Reiko Hanada, Andreas Leibbrandt, Shiho Kitaoka, Tomoyuki Furuyashiki, Hiroaki Fujihara, John Trichereau, Magdalena Paolino, Michael Bader, Hironobu Yoshimatsu, Sara Sebnem Kilic, Yoichi Ueta, Christian Pifl, Shuh Narumiya, Josef M. Penninger

  Mar. 2010, ENDOCRINE JOURNAL, 57, S538 - S539, English

  Summary international conference


• Roles of prostanoid in stress responses

  古屋敷 智之, 成宮 周

  医歯薬出版, 02 Jan. 2010, 医学のあゆみ, 232(1) (1), 68 - 73, Japanese


• Roles of prostaglandin E2, a proinflammatory mediator, in emotional adaptation to stress

  Tomoyuki Furuyashiki, Kohei Tanaka, Shiho Kitaoka, Shuh Narumiya

  2010, NEUROSCIENCE RESEARCH, 68, E47 - E47, English

  Summary international conference


• tProstaglandin E receptor EP1 induces intracellular accumulation of dopamine D1 receptor and facilitates dopamine D1 receptor signaling in a Ca2+-independent manner

  Aliza T. Ehrlich, Tomoyuki Furuyashiki, Shiho Kitaoka, Shuh Narumiya

  2010, NEUROSCIENCE RESEARCH, 68, E121 - E121, English

  Summary international conference


• Roles of thromboxane receptor in dopamine signaling in the striatum

  Tomoyuki Mitsumori, Tomoyuki Furuyashiki, Shiho Kitaoka, Haruhisa Inoue, Toshiyuki Matsuoka, Shuh Narumiya

  2010, JOURNAL OF PHARMACOLOGICAL SCIENCES, 112, 190P - 190P, English

  Summary international conference


• Roles of prostaglandin E2-EP4 signaling in functional hyperemia in the brain

  Tomohiro Aoki, Tomoyuki Furuyashiki, Akira Takatsuki, Akitoshi Seiyama, Shuh Narumiya

  2010, NEUROSCIENCE RESEARCH, 68, E355 - E355, English

  Summary international conference


• Roles of mDia isoforms, a Rho effector, in neural development

  Ryota Shinohara, Dean Thumkeo, Hiroshi Kamijo, Naoko Kaneko, Kazunobu Sawamoto, Hiroyuki Hioki, Takeshi Kaneko, Keisuke Watanabe, Hirohide Takebayashi, Toshimasa Ishizaki, Tomoyuki Furuyashiki, Shuh Narumiya

  2010, NEUROSCIENCE RESEARCH, 68, E138 - E138, English

  Summary international conference


• Roles of prostaglandin E2 and its receptor EP1 in adaptive selection of emotional behaviors

  Tomoyuki Furuyashiki, Kohei Tanaka, Shiho Kitaoka, Yasuhiro Tanaka, Tomoyuki Mitsumori, Aliza Ehrlich, Shuh Narumiya

  2010, JOURNAL OF PHARMACOLOGICAL SCIENCES, 112, 123P - 123P, English

  Summary international conference


• Roles of prostaglandin E2 and its receptor EP1 in social withdrawal due to repeated social defeat in mice

  Kohei Tanaka, Shiho Kitaoka, Tomoyuki Furuyashiki, Shuh Narumiya

  2010, JOURNAL OF PHARMACOLOGICAL SCIENCES, 112, 190P - 190P, English

  Summary international conference


• Roles of prostaglandin E2 and its receptor EP1 in social withdrawal after repeated social defeat in mice

  Kohei Tanaka, Shiho Kitaoka, Tomoyuki Furuyashiki, Shuh Narumiya

  2010, NEUROSCIENCE RESEARCH, 68, E171 - E171, English

  Summary international conference


• Roles of thromboxane receptor in dopaminergic signaling in the striatum

  Tomoyuki Mitsumori, Tomoyuki Furuyashiki, Shiho Kitaoka, Haruhisa Inoue, Toshiyuki Matsuoka, Shuh Narumiya

  2010, NEUROSCIENCE RESEARCH, 68, E235 - E235, English

  Summary international conference


• Two opposite actions of prostaglandin E receptor EP1 on dopamine D1 receptor signaling

  Aliza Ehrlich, Tomoyuki Furuyashiki, Shiho Kitaoka, Shuh Narumiya

  2010, JOURNAL OF PHARMACOLOGICAL SCIENCES, 112, 190P - 190P, English

  Summary international conference


• Roles of mDia, a Rho effector, in neural development

  Ryota Shinohara, Hiroshi Kamijo, Hiroyuki Hioki, Takeshi Kaneko, Toshimasa Ishizaki, Tomoyuki Furuyashiki, Shuh Narumiya

  2009, NEUROSCIENCE RESEARCH, 65, S95 - S95, English

  Summary international conference


• Prostaglandin E-2 acts on EP1 receptor and amplifies both dopamine D1 and D2 receptor signaling in the striatum

  Shiho Kitaoka, Tomoyuki Furuyashiki, Akinori Nishi, Takahide Shuto, Sho Koyasu, Toshiyuki Matsuoka, Masayuki Miyasaka, Paul Greengard, Shuh Narumiya

  2008, JOURNAL OF PHARMACOLOGICAL SCIENCES, 106, 67P - 67P, English

  Summary international conference


• Rodent orbitofrontal cortex separately encodes response and outcome information during performance of goal-directed behavior

  Tomoyuki Furuyashiki, Aliza T. Ehrlich, Peter C. Holland, Michela Gallagher

  2008, NEUROSCIENCE RESEARCH, 61, S261 - S261, English

  Summary international conference


• Prostaglandin E receptor EP1 enhances GABA-mediated inhibition of dopaminergic neurons in the substantia nigra and suppresses dopamine level in dorsal striatum

  Yasuhiro Tanaka, Tomoyuki Furuyashiki, Toshiyuki Matsuoka, Tetsurou Kayahara, Toshihiko Momiyama, Hisaaki Namba, Tomoyuki Mitsumori, Hitoshi Shichi, Kazushi Kimura, Hiroyuki Nawa, Akira Mizoguchi, Shuh Narumiya

  2008, JOURNAL OF PHARMACOLOGICAL SCIENCES, 106, 231P - 231P, English

  Summary international conference


• Prostaglandin E receptor EP1 enhances GABA-mediated inhibition of dopaminergic neurons in the substantia nigra and suppresses dopamine level in dorsal striatum

  Tomoyuki Mitsumori, Yasuhiro Tanake, Tomoyuki Furuyashiki, Toshiyuki Matsuoka, Tetsurou Kayahara, Toshihiko Momiyama, Hisaaki Namba, Hitoshi Shichi, Kazushi Kimura, Hiroyuki Nawa, Akira Mizoguchi, Shuh Narumiya

  2008, NEUROSCIENCE RESEARCH, 61, S221 - S221, English

  Summary international conference


• Facilitation of Th1-mediated immune response by prostaglandin E receptor EP1

  Daiji Sakata, Miyako Nagamachi, Kenji Kabashima, Tomoyuki Furuyashiki, Kitipong Soontrapa, Toshiyuki Matsuoka, Eri Segi-Nishida, Shuh Narumiya

  2008, JOURNAL OF PHARMACOLOGICAL SCIENCES, 106, 94P - 94P, English

  Summary international conference


• Prostaglandin E receptor EP1 amplifies dopaminergic signaling in the striatum

  Shiho Kitaoka, Tomoyuki Furuyashiki, Akinori Nishi, Takahide Shuto, Sho Koyasu, Toshiyuki Matsuoka, Paul Greengard, Shuh Narumiya

  2008, NEUROSCIENCE RESEARCH, 61, S81 - S81, English

  Summary international conference


• PGE(2)-EP1 signaling facilitate Th1 immune response

  Daiji Sakata, Miyako Nagamachi, Kenji Kabashima, Tomoyuki Furuyashiki, Kitipong Soontrapa, Toshiyuki Matsuoka, Eri Segi-Nishida, Shuh Narumiya

  2007, JOURNAL OF PHARMACOLOGICAL SCIENCES, 103, 55P - 55P, English

  Summary international conference


• Prostaglandin e receptor subtype EP1 regulates dopamine receptor signaling in the striatum.

  Shiho Kitaoka, Tomoyuki Furuyashiki, Akinori Nishi, Takahide Shuto, Sho Koyasu, Toshiyuki Matsuoka, Shuh Narumiya

  2007, JOURNAL OF PHARMACOLOGICAL SCIENCES, 103, 135P - 135P, English

  Summary international conference


• PGE2 receptor EP1 enhance Th1 differentiation

  D Sakata, M Nagamachi, K Kabashima, T Furuyashiki, E Segi-Nishida, S Narumiya

  2006, JOURNAL OF PHARMACOLOGICAL SCIENCES, 100, 93P - 93P, English

  Summary international conference


• Prostaglandin E2 potentiates dopamine D1 receptor signaling via EP1

  Shiho Kitaoka, Sho Koyasu, Akinori Nishi, Tomoyuki Furuyashiki, Toshiyuki Matsuoka, Shuh Narumiya

  2006, NEUROSCIENCE RESEARCH, 55, S170 - S170, English

  Summary international conference


• Prostaglandin E-2 potentiates D1R signaling via EP1

  S Kitaoka, S Koyasu, Y Tanaka, A Nishi, T Furuyashiki, T Matsuoka, M Miyasaka, S Narumiya

  2006, JOURNAL OF PHARMACOLOGICAL SCIENCES, 100, 193P - 193P, English

  Summary international conference


• Prostaglandin E-2 modulates midbrain dopaminergic system via its receptor EP1

  Y Tanaka, T Furuyashiki, T Matsuoka, S Kitaoka, T Nagai, K Yamada, A Mizoguchi, A Nishi, T Nabeshima, S Narumiya

  2005, JOURNAL OF PHARMACOLOGICAL SCIENCES, 97, 273P - 273P, English

  Summary international conference


• Prostaglandin E receptor EP1 regulates dopamine release in vivo

  Y Tanaka, T Furuyashiki, A Mizoguchi, S Narumiya

  2004, JOURNAL OF PHARMACOLOGICAL SCIENCES, 94, 228P - 228P, English

  Summary international conference


• Prostanoid receptor-dependent mechanism regulating stress-related behaviors

  T Furuyashiki, Y Matsuoka, A Mizoguchi, S Narumiya

  2004, JOURNAL OF PHARMACOLOGICAL SCIENCES, 94, 56P - 56P, English

  Summary international conference


• Behavioral approaches for emotion in the prostaglandin E receptor mutant mice

  T Nagai, T Furuyashiki, S Narumiya, T Nabeshima

  2004, JOURNAL OF PHARMACOLOGICAL SCIENCES, 94, 18P - 18P, English

  Summary international conference


• 「神経再生移植(2)」低分子量G蛋白Rho情報伝達系操作による機能的神経再生の可能性の探索:軸索伸展制御機構の解析

  荒川芳輝, 尾藤晴彦, 古屋敷智之, 山名則和, 竹本(木村)さやか, 野崎和彦, 成宮周, 橋本信夫

  2003, 日本脳神経外科学会総会抄録集, 62nd(CD-ROM Abstracts) (CD-ROM Abstracts)


• Dynamic and activity-dependent control of neuronal actin cytoskeleton.

  H Bito, Y Arakawa, T Furuyashiki, S Takemoto-Kimura, S Narumiya

  2003, JOURNAL OF PHARMACOLOGICAL SCIENCES, 91, 21P - 21P, English

  Summary international conference


• 新規CREB kinase CLICK-I&IIによるCREB抑制の可能性

  大前彰吾, 竹本(木村)さやか, 古屋敷智之, 丹治正大, 喜久村祥子, 荒川芳輝, 成宮周, 尾藤晴彦

  2002, 生化学, 74(8) (8)


• RhoGTPase effector mDia1の軸索伸展過程における役割の解析

  荒川芳輝, 尾藤晴彦, 古屋敷智之, 竹本(木村)さやか, 辻隆宏, 石崎敏理, 野崎和彦, 橋本信夫, 成宮周

  2002, 日本神経科学大会プログラム・抄録集, 25th


• 海馬神経細胞におけるCa²⁺とアクチン細胞骨格の時間的・空間的制御

  古屋敷智之, 荒川芳輝, 竹本(木村)さやか, 尾藤晴彦, 成宮周

  2002, 日本神経科学大会プログラム・抄録集, 25th


• Rho 情報伝達系操作により機能的神経再生ができるか?:Rho 情報伝達系による軸索伸展制御機構の解析

  荒川芳輝, 尾藤晴彦, 古屋敷智之, 辻隆宏, 竹本さやか, 石崎敏理, 野崎和彦, 成宮周, 橋本信夫

  2002, 日本脳神経外科学会総会抄録集, 61st(CD-ROM Abstracts) (CD-ROM Abstracts)


• 新規CaM kinase CLICK-IIIのクローニング及び解析

  竹本(木村)さやか, 大前彰吾, 古屋敷智之, 荒川芳輝, 喜久村祥子, 成宮周, 尾藤晴彦

  2002, 日本神経科学大会プログラム・抄録集, 25th


• 新規CREBキナーゼCLICK-IIIによるCREB活性化機構

  竹本(木村)さやか, 大前彰吾, 古屋敷智之, 荒川芳輝, 喜久村祥子, 成宮周, 尾藤晴彦

  2002, 生化学, 74(8) (8)


• Citron, a Rho target, interacts with PSD-95 at glutamatergic synapses in the thalamus

  FURUYASHIKI Tomoyuki, FUJISAWA Kazuko, FUJITA Akiko, MADAULE Pascal, KIKUMURA Shoko, UCHINO Shigeo, MISHINA Masayoshi, BITO Haruhiko, NARUMIYA Shuh

  01 Dec. 1998, 日本分子生物学会年会プログラム・講演要旨集, 21, 643 - 643, Japanese


• Neuronal CREB signaling and synaptic Ca^<2+> influx

  BITO Haruhiko, TSIEN Richard W., FURUYASHIKI Tomoyuki, UCHINO Shigeo, MISHINA Masayoshi, NARUMIYA Shuh

  01 Dec. 1998, 日本分子生物学会年会プログラム・講演要旨集, 21, 199 - 199, Japanese

• Bioactive Lipid Mediators Current Reviews and Protocols

  Furuyashiki T, Kitaoka S

  Joint work, Part III Lipid Mediators and Diseases, 22. Roles and actions of arachidonic acid-derived bioactive lipids in stress-related behaviors., Springer, Nov. 2015, 315-328

• INTERNATIONAL COLLEGE OF NEUROPSYCHOPHARMACOLOGY


• SOCIETY FOR NEUROSCIENCE


• JAPANESE ASSOCIATION FOR THE STUDY OF PAIN


• THE JAPANESE SOCIETY OF INFLAMMATION AND REGENERATION


• THE JAPANESE SOCIETY OF NEUROPSYCHOPHARMACOLOGY


• THE JAPANESE SOCIETY FOR NEUROCHEMISTRY


• THE JAPANESE PHARMACOLOGICAL SOCIETY


• THE JAPAN NEUROSCIENCE SOCIETY


• THE MOLECULAR BIOLOGY SOCIETY OF JAPAN


• THE JAPANESE BIOCHEMICAL SOCIETY


• Psychoneuroimmunology research society


• JAPANESE SOCIETY OF BIOLOGICAL PSYCHIATRY