Research activity information

• 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


• 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

  [Refereed]

  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

  [Refereed]

  Scientific journal


• Memantine ameliorates the impairment of social behaviors induced by a single social defeat stress as juveniles

  Mikio Yoshida, Sho Hasegawa, Masayuki Taniguchi, Akihiro Mouri, Chiharu Suzuki, Akira Yoshimi, Takayoshi Mamiya, Norio Ozaki, Yukihiro Noda

  Elsevier BV, Oct. 2022, Neuropharmacology, 217, 109208 - 109208

  [Refereed]

  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

  [Refereed]


• Early postnatal inhibition of GLAST causes abnormalities of psychobehaviors and neuronal morphology in adult mice

  Mizuki Uchida, Yukihiro Noda, Sho Hasegawa, Hirotake Hida, Masayuki Taniguchi, Akihiro Mouri, Akira Yoshimi, Toshitaka Nabeshima, Kiyofumi Yamada, Tomomi Aida, Kohichi Tanaka, Norio Ozaki

  The importance of glutamate transporters in learning, memory, and emotion remains poorly understood; hence, in the present study, we investigated whether deficiency of pharmacological GLAST in neurodevelopmental processes affects cognitive and/or emotional behaviors in mice. The mice were injected with a glutamate transporter inhibitor, dl-threo-β-benzyloxyaspartate (dl-TBOA), during the early postnatal period. At 8 weeks of age, they showed impairments in cognitive or emotional behaviors; dysfunction of glutamatergic neurotransmission (increased expressions of GLAST, GLT-1, or GFAP protein, and decreased ability of glutamate release) in the cortex or hippocampus; morphological changes (decreased cell size in the cortex and thickness of the pyramidal neuronal layer of the CA1 area in the hippocampus). Such behavioral and morphological changes were not observed in adult mice injected with dl-TBOA. These results suggest that GLAST plays an important role in the regulation of cognitive and emotional behaviors. Early postnatal glutamatergic facilitation by GLAST dysfunction leads to cognitive and emotional abnormalities due to neurodevelopmental abnormalities such as morphological changes.

  Elsevier BV, Nov. 2021, Neurochemistry International, 150, 105177 - 105177, English, International magazine

  [Refereed]

  Scientific journal


• 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

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

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• The Innate Immune Receptors TLR2/4 Mediate Repeated Social Defeat Stress-Induced Social Avoidance through Prefrontal Microglial Activation.

  Nie X, KITAOKA SHIHO, 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)


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

  Higashida S, Nagai H, Nakayama K, Shinohara R, Taniguchi M, Nagai M, Hikida T, Yawata S, Ago Y, Kitaoka S

  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.

  Nature Publishing Group, Jul. 2018, Scientific Reports, 8(1) (1), 10454 - 10454, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Juvenile social defeat stress exposure persistently impairs social behaviors and neurogenesis.

  Mouri A, Ukai M, Uchida M, Hasegawa S, Taniguchi M, Ito T, Hida H, Yoshimi A, Yamada K, Kunimoto S, Ozaki N, Nabeshima T, Noda Y

  Mar. 2018, Neuropharmacology, 133, 23 - 37, English

  [Refereed]

  Scientific journal


• Blonanserin ameliorates phencyclidine-induced visual-recognition memory deficits: The complex mechanism of blonanserin action involving D<inf>3</inf>-5-HT<inf>2A</inf> and D 1-NMDA receptors in the mPFC

  Hirotake Hida, Akihiro Mouri, Kentaro Mori, Yurie Matsumoto, Takeshi Seki, Masayuki Taniguchi, Kiyofumi Yamada, Kunihiro Iwamoto, Norio Ozaki, Toshitaka Nabeshima, Yukihiro Noda

  Nature Publishing Group, 2015, Neuropsychopharmacology, 40(3) (3), 601 - 613, English

  [Refereed]

  Scientific journal

• 精神疾患と炎症応答

  谷口将之, 古屋敷智之

  Lead, Jul. 2022, 医学のあゆみ, 282(1) (1), 2 - 8, Japanese


• ストレスによる炎症応答のメカニズムとその役割

  谷口将之, 北岡志保, 古屋敷智之

  Lead, Jan. 2021, 生体の科学, 72(5) (5), 389 - 392, Japanese

  Introduction scientific journal


• 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


• ストレス抵抗性における内側前頭前皮質ドパミン系の役割と神経細胞形態変化の関与

  Taniguchi Masayuki, Shinohara Ryota, Furuyashiki Tomoyuki

  2018, 日本生物学的精神医学会誌, 29(1) (1), 27 - 33, Japanese

  [Refereed]

  Introduction other


• 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


• 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


• 幼若期慢性社会的敗北ストレス負荷が社会性行動とモノアミン作動性神経に与える影響

  三宅 裕里子, 長谷川 章, 毛利 彰宏, 谷口 将之, 肥田 裕丈, 吉見 陽, 尾崎 紀夫, 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, 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, 209 - 209, Japanese


• 幼若期マウスへの社会敗北ストレス負荷による社会性行動障害と神経新生低下におけるグルココルチコイドの関与

  谷口 将之, 鵜飼 麻由, 肥田 裕丈, 長谷川 章, 森 健太郎, 山田 清文, 鍋島 俊隆, 尾崎 紀夫, 毛利 彰宏, 野田 幸裕

  (公社)日本薬理学会, Nov. 2013, 日本薬理学雑誌, 142(5) (5), 12P - 12P, Japanese


• 日-P1-058 病院実務実習における医療用麻薬の適正使用に関する知識習得度の調査(薬学教育(実務実習),ポスター発表,一般演題,再興、再考、創ろう最高の医療の未来)

  土屋 翔子, 小谷 悠, 椿井 朋, 永井 智子, 谷口 将之, 小池 孝洋, 鈴木 守人, 浅井 玲名, 平林 彩, 室崎 千尋, 鵜飼 麻由, 荻野 由里恵, 櫛田 真由, 後藤 綾, 山下 加織, 肥田 裕丈, 宮崎 雅之, 毛利 彰宏, 野田 幸裕

  日本医療薬学会, 28 Aug. 2013, 日本医療薬学会年会講演要旨集, 23, 362 - 362, Japanese


• 薬学生主体の児童向け出前くすり実験授業において薬学生が得た成果

  肥田 裕丈, 櫛田 真由, 小谷 悠, 水野 智博, 土屋 翔子, 永井 智子, 谷口 将之, 山下 加織, 鵜飼 麻由, 後藤 綾, 荻野 由里恵, 松本 友里恵, 椿井 朋, 毛利 彰宏, 鍋島 俊隆, 野田 幸裕

  (公社)日本薬学会, Mar. 2013, 日本薬学会年会要旨集, 133年会(4) (4), 234 - 234, Japanese


• 児童向け出前くすり実験授業の有用性

  永井 智子, 櫛田 真由, 小谷 悠, 水野 智博, 肥田 裕丈, 土屋 翔子, 谷口 将之, 山下 加織, 鵜飼 麻由, 後藤 綾, 荻野 由里恵, 松本 友里恵, 毛利 彰宏, 鍋島 俊隆, 野田 幸裕

  (公社)日本薬学会, Mar. 2013, 日本薬学会年会要旨集, 133年会(4) (4), 234 - 234, Japanese


• 薬学生主導型児童向け出前くすり実験授業 薬学生への有用性

  肥田 裕丈, 櫛田 真由, 小谷 悠, 水野 智博, 土屋 翔子, 永井 智子, 谷口 将之, 山下 加織, 鵜飼 麻由, 後藤 綾, 荻野 由里恵, 石川 ゆり, 伊藤 美那子, 松本 友里恵, 飯田 耕太郎, 間宮 隆吉, 毛利 彰宏, 鍋島 俊隆, 野田 幸裕

  (一社)愛知県病院薬剤師会, Mar. 2013, APJHP: 愛知県病院薬剤師会雑誌, 40(4) (4), 7 - 10, Japanese


• Juvenile social defeat impairs social behaviors in adult: involvement of glucocorticoid and neurogenesis

  Mayu Ukai, Akihiro Mouri, Taniguchi Masayuki, Hirotake Hida, Yu Ando, Akira Yoshimi, Toshitaka Nabeshima, Norio Ozaki, Yukihiro Noda

  2013, JOURNAL OF PHARMACOLOGICAL SCIENCES, 121, 224P - 224P, English

  Summary international conference


• 【統合失調症の最新研究】統合失調症のモデル動物 行動薬理学的妥当性

  毛利 彰宏, 谷口 将之, 野田 幸裕, 鍋島 俊隆

  (株)ライフ・サイエンス, Nov. 2012, Progress in Medicine, 32(11) (11), 2339 - 2350, 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


• Combination of a neonatal viral infection with an adolescent substance use affect psychological function in adult

  HIDA H, MOURI A, TANIGUCHI M, UKAI A, OZAKI N, YAMADA K, NABESHIMA T, NODA Y

  (一社)日本神経精神薬理学会, 25 Apr. 2012, 日本神経精神薬理学雑誌 = Japanese journal of psychopharmacology, 32(2) (2), 101 - 103, Japanese


• Influence of social defeat stress during the juvenile period on the social behaviors and monoaminergic or endocrine systems in mice

  Mayu Ukai, Yu Ando, Akihiro Mouri, Hirotake Hida, Masayuki Taniguchi, Akira Yoshimi, Kiyofumi Yamada, Toshitaka Nabeshima, Norio Ozaki, Yukihiro Noda

  2012, JOURNAL OF PHARMACOLOGICAL SCIENCES, 118, 189P - 189P, English

  Summary international conference

• ミクログリアのストレス応答における 転写・エピゲノム制御

  谷口将之, 古屋敷智之

  第44回日本炎症再生医学会, Jul. 2023, Japanese

  Nominated symposium


• ミクログリアはToll様受容体2/4とグルココルチコイド受容体 を介してストレス期間とストレス感受性を 統合し情動変容を誘導する

  谷口将之, 松下和敏, 三島零, 北岡志保, 工樂樹洋, 門田満隆, 古屋敷智之

  第143回日本薬理学会近畿部会, May 2023, Japanese

  Oral presentation


• ストレスによるミクログリアの転写・ エピゲノム応答とその役割

  谷口将之, 古屋敷智之

  次世代薬理学セミナー 2023 in 東京, Mar. 2023, Japanese

  [Invited]

  Public discourse


• Transcriptional machinery of microglial stress response

  Masayuki Taniguchi, Furuyashiki Tomoyuki

  第96回日本薬理学会年会（JWP2022）, Dec. 2022, Japanese

  Public symposium


• Stress-induced transcriptional and epigenetic landscape of microglia

  Masayuki Taniguchi, Tomoyuki Furuyashiki

  BPCNPNPPP4合同年会, Oct. 2022, Japanese

  Public symposium


• Transcriptional and epigenetic regulations of microglia for stress responses

  Masayuki Taniguchi, Kazutoshi Matsushita, Rei Mishima, Shiho Kitaoka, Shigehiro Kuraku, Mitsutaka Kadota, Tomoyuki Furuyashiki

  NEURO2022, Jul. 2022, English

  Poster presentation


• Transcriptional programs of microglia for integrating brain and peripheral stress responses

  Masayuki Taniguchi, Tomoyuki Furuyashiki

  The 95th Annual Meeting of Japanese Pharmacological Society, Mar. 2022, Japanese

  Public symposium


• Transcriptional and epigenetic regulations of microglia for local and global stress responses

  Masayuki Taniguchi, Kazutoshi Matsushita, Rei Mishima, Shiho Kitaoka, Shigehiro Kuraku, Mitsutaka Kadota, Tomoyuki Furuyashiki

  The 44th Annual Meeting of the Japan Neuroscience Society, Jul. 2021

  Poster presentation


• ミクログリアのストレス応答を担う転写・エピゲノム制御

  谷口将之, 松下和敏, 三島零, 北岡志保, 工樂樹洋, 門田満隆, 古屋敷智之

  第139回日本薬理学会近畿部会, Jun. 2021

  Oral presentation


• Multiple spatiotemporal patterns of social stress-induced epigenetic regulations in microglia

  Masayuki Taniguchi, Kazutoshi Matsushita, Rei Mishima, Shiho Kitaoka, Shigehiro Kuraku, Mitsutaka Kadota, Tomoyuki Furuyashiki

  The 94th Annual Meeting of the Japanese Pharmacological Society, Mar. 2021

  Oral presentation


• 社会ストレスによるミクログリアのエピゲノム制御における多様な時空間的パターン

  谷口 将之

  第13回K-CONNEX研究会, Feb. 2021

  Oral presentation


• 次世代シークエンサーを用いたオミクス解析

  谷口 将之

  シグナル伝達医学研究展開センター（CSMI）1st Emergence Conference, Dec. 2020

  Oral presentation


• 反復ストレスによるミクログリアのエピゲノム変化の解析

  谷口 将之

  2020年度 Neuro science Network in Kobe 秋の会, Nov. 2020

  Oral presentation


• Analysis of epigenetic regulation in social defeat stress-induced microglial activation

  谷口将之, 北岡志保, 門田満隆, 工樂樹洋, 古屋敷智之

  新学術領域 マルチスケール精神病態の構成的理解 第3回領域会議, Jul. 2020

  Poster presentation


• Epigenomic regulation of prefrontal microglia induced by social defeat stress

  谷口将之, 北岡志保, 門田満隆, 工樂樹洋, 古屋敷智之

  第93回 日本薬理学会, Mar. 2020

  Poster presentation


• 社会挫折ストレスにより誘導される内側前頭前皮質ミクログリアのエピゲノム変化の解析

  谷口 将之

  シグナル伝達医学研究展開センター(CSMI)主催 若手研究者リトリート「若手道場」, Feb. 2020, English

  Oral presentation


• Analysis of epigenetic changes in prefrontal microglia induced by repeated social defeat stress

  Masayuki Taniguchi, Shiho Kitaoka, Shigehiro Kuraku, Mitsutaka Kadota, Tomoyuki Furuyashiki

  University of Washington Department of Pharmacology 2019 Symposium on Molecular Pharmacology, Sep. 2019, English

  Poster presentation


• 反復社会挫折ストレスによる前頭前皮質ミクログリアのエピゲノム制御

  谷口将之, 北岡志保, 門田満隆, 工樂樹洋, 古屋敷智之

  NEURO2019（第42回日本神経科学大会・第62回日本神経化学会大会）, Jul. 2019, English

  Poster presentation


• 反復ストレスによる内側前頭前皮質ミクログリアのエピゲノム制御

  TANIGUCHI MASAYUKI

  第9回K-CONNEX研究会, Mar. 2019, Japanese, 神戸市, Domestic conference

  Oral presentation


• マウス反復社会挫折ストレスによる前頭前皮質ミクログリアのエピゲノム変化の解析

  TANIGUCHI MASAYUKI, KITAOKA SHIHO, 門田 満隆, 工樂 樹洋, FURUYASHIKI TOMOYUKI

  第92回日本薬理学会年会, Mar. 2019, Japanese, 大阪市, Domestic conference

  Poster presentation


• マウスの社会挫折ストレスにより誘導される情動変容の多面的解析：社会忌避と不安亢進の解離

  NAGAI HIROTAKA, 東田 崇, 中山 和紀, SHINOHARA RYOTA, TANIGUCHI MASAYUKI, 永井 碧, 疋田 貴俊, 矢和多 智, 吾郷 由希夫, KITAOKA SHIHO, 成宮 周, FURUYASHIKI TOMOYUKI

  第92回日本薬理学会年会, Mar. 2019, Japanese, 大阪, Domestic conference

  Poster presentation


• ストレスによる脳内変化の実体とその役割に迫る

  TANIGUCHI MASAYUKI

  第14回KRPアイデア・シェアリング・コミュニティ, Mar. 2019, Japanese, 京都市, Domestic conference

  [Invited]

  Invited oral presentation


• 反復社会挫折ストレスにより誘導される前頭前皮質ミクログリアのエピゲノム変化の解析

  TANIGUCHI MASAYUKI, KITAOKA SHIHO, 門田 満隆, 工樂 樹洋, FURUYASHIKI TOMOYUKI

  新学術領域 マルチスケール精神病態の構成的理解 第1回領域会議, Feb. 2019, Japanese, 安中市, Domestic conference

  Poster presentation


• 反復ストレスによる内側前頭前皮質ミクログリアのエピゲノム制御の解析

  TANIGUCHI MASAYUKI

  シグナル伝達医学研究展開センター若手道場, Feb. 2019, Japanese, 淡路市, Domestic conference

  Oral presentation


• Analysis of epigenomic changes in prefrontal microglia induced by repeated social defeat stress.

  Masayuki Taniguchi, Shiho Kitaoka, Shigehiro Kuraku, Mitsutaka Kadota, Tomoyuki Furuyashiki

  第２回 神戸理研 神戸大学合同シンポジウム, Jan. 2019, Japanese, 神戸市, Domestic conference

  Poster presentation


• マウス反復社会挫折ストレスにより誘導されるミクログリアのエピゲノム解析

  Taniguchi Masayuki, Kitaoka Shiho, Kadota Mitsutaka, Kuraku Shigehiro, Furuyashiki Tomoyuki

  第134回日本薬理学会近畿部会, Nov. 2018, Japanese, Domestic conference

  Oral presentation


• マウス社会挫折ストレスにおける内側前頭前皮質ミクログリアのエピゲノム解析

  Taniguchi Masayuki

  K-CONNEX 平成30年度 成果報告会, Nov. 2018, Japanese, 大阪市, Domestic conference

  Invited oral presentation


• D1 receptor subtype mediates acute stress-induced dendritic growth of excitatory neurons and gene expression changes associated with stress resilience in the medial prefrontal cortex

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

  WCP2018, Jul. 2018, English, International conference

  Poster presentation


• マウスの社会挫折ストレスにより誘導される情動変容の多面的解析：社会忌避と不安亢進の解離

  NAGAI HIROTAKA, 東田 崇, 中山 和紀, SHINOHARA RYOTA, TANIGUCHI MASAYUKI, 永井 碧, 疋田 貴俊, 矢和多 智, 吾郷 由希夫, KITAOKA SHIHO, 成宮 周, FURUYASHIKI TOMOYUKI

  第133回日本薬理学会近畿部会, Jun. 2018, Japanese, 広島, Domestic conference

  Oral presentation


• 内側前頭前皮質のドパミンD1受容体によるストレス抵抗性増強と神経細胞形態制御

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

  第132回日本薬理学会近畿部会, Nov. 2017, Japanese, Domestic conference

  Oral presentation


• Dopamine D1 receptor mediates social defeat stress-induced dendritic growth in excitatory neurons of the medial prefrontal cortex and regulates stress-induced behavioral resilience in mice

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

  The 60th annual meeting of Japanese Society for Neurochemistry, Sep. 2017, Japanese, Domestic conference

  Oral presentation


• A role of dopamine D1 receptor in the medial prefrontal cortex in acute stress-induced emotional response

  谷口 将之, 篠原 亮太, エーリック アリザ, 横川 賢多朗, 成宮 周, Furuyashiki Tomoyuki

  第38回日本神経科学大会, Jul. 2015, Japanese, The Japan Neuroscience Society, 神戸, Domestic conference

  Poster presentation

• ミクログリアによる情動変容を担う脳内組織恒常性の維持とその破綻機構の解明

  谷口 将之

  日本学術振興会, 科学研究費助成事業, 若手研究, 神戸大学, 01 Apr. 2021 - 31 Mar. 2023

  うつ病など精神疾患の発症には遺伝的素因に加えて環境要因が関わる。研究代表者らはマウス社会挫折ストレスを用い、反復ストレスは情動変容に伴う内側前頭前皮質の神経細胞樹状突起の萎縮を誘導すること、この変化には内側前頭前皮質特異的なミクログリアの活性化が関わることを示した。これらの知見からストレスによる情動変容はミクログリアの活性化に端を発した組織恒常性の破綻によると推測されるが、その実態は不明である。本研究では、ストレスにおける組織恒常性の維持とその破綻の分子基盤を解明し、うつ病などストレス性疾患の病態機序解明や新たな創薬標的創出に資する知見を得る。 本年度は、単回・反復社会挫折ストレスに供したマウスの内側前頭前皮質と側坐核のミクログリアのトランスクリプトーム解析（RNA-seq）、エピゲノム解析（ChIP-seq、ATAC-seq）のデータからストレスによるミクログリアの変化の実体とその分子メカニズムを探索し、ミクログリアのストレス応答に関与する転写・エピゲノム制御因子やシグナル伝達分子の候補を同定した。関与が推定された転写・エピゲノム制御因子やシグナル伝達分子の阻害操作を実施し、この操作がミクログリアにおいてストレスによる遺伝子発現変化を消失させること、ストレスによる情動変容を阻害することを示した。薬理学実験などで対応が難しい転写・エピゲノム制御因子については欠損マウスの作出も進めた。さらに、内側前頭前皮質の全細胞集団の解析のための単一細胞遺伝子発現解析の最適化を実施し、実測定のための準備を整えた。


• Elucidation of mechanisms for regulating microglial activation underlying brain microenvironmental deterioration

  Masayuki Taniguchi

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists, Kobe University, 01 Apr. 2019 - 31 Mar. 2021

  Social stress often induces emotional alterations such as depression and anxiety, and can be a risk factor for mental illness. However, the mechanism remains unknown. Recently studies suggest that chronic stress induces neuroinflammation through microglia activation. Using a mouse model of social defeat stress, here we found that repetition of stress exposure induces brain region-specific epigenomic changes in microglia and these epigenetic changes are concordant with the expression of adjacent genes associated with different biological functions. Furthermore, we specified transcription factors associated with epigenomic changes. These results suggest that stress induces epigenomic changes in microglia, which may contribute to neuroinflammation for emotional disturbances.


• 前頭前皮質ドパミン系によるストレス抵抗性増強を担う神経回路とその分子機序の解明

  谷口 将之

  日本学術振興会, 科学研究費助成事業, 特別研究員奨励費, 26 Apr. 2017 - 31 Mar. 2019

  社会挫折や孤独から受けるストレスは、抑うつや不安亢進など情動変容を惹き起し、精神疾患のリスク因子となる。我々は社会挫折ストレスを用い、単回ストレスは内側前頭前皮質（mPFC）のドパミンD1受容体サブタイプを介してmPFC神経細胞の樹状突起やスパインを造成してストレス抵抗性を増強することを示してきた。本研究では、社会挫折ストレスを用い、ストレス抵抗性増強を担う神経回路とmPFC神経細胞の機能・形態的増強の機序を解明することを目的としている。 本年度は、昨年度に引き続き、即時応答遺伝子（cFos）の免疫染色によりストレス抵抗性増強に関与する脳領域を解析した。その結果、探索行動により活性化する脳領域と単回ストレスにより活性化する脳領域を見出した。mPFC特異的なドパミンD1受容体発現抑制マウスを作出し単回ストレスに供したところ、ストレスにより活性化する脳領域の一部でその活性化が消失していた。さらに、この脳領域に蛍光タンパク質を発現する逆行性感染性ウイルスベクターを注入したところ、mPFCの神経細胞が標識された。以上の結果は、本解析により同定した脳領域へのmPFCからの神経投射がストレス抵抗性増強を担う可能性を示唆する（沼ら 論文投稿中）。また、本年度は、昨年度までに確立した機能制御実験系を用いて形態制御因子がストレス抵抗性の増強に関与するかについて解析した。野生型マウスでは、反復ストレスにより社会忌避行動が誘導されたが、形態制御因子発現抑制マウスでは反復ストレスにより誘導される社会忌避行動の誘導が減弱していた。本結果は、ドパミンD1受容体を介して誘導される形態制御因子がストレス抵抗性増強に関与する可能性を推測させる。以上の成果により、ドパミンD1受容体によるストレス抵抗性を増強する神経回路と、樹状突起造成のメカニズムやその意義を提示した。