Directory of Researchers

WAKE Hiroaki
Organization for Advanced and Integrated Research
Professor
Medicine
Last Updated :2020/08/05

Researcher Profile and Settings

Affiliation

  • <Faculty / Graduate School / Others>

    Organization for Advanced and Integrated Research
  • <Related Faculty / Graduate School / Others>

    School of Medicine, Graduate School of Medicine

Teaching

  • Graduate School of Medicine / Faculty of Biomedical Sciences, 2019, Basic Course of Bioscience
  • Graduate School of Medicine / Faculty of Biomedical Sciences, 2019, Biomedical ScienceA
  • Graduate School of Medicine / Faculty of Biomedical Sciences, 2019, Research in Biomedical Science
  • Graduate School of Medicine / Faculty of Biomedical Sciences, 2019, Literature Analysis and Presentation
  • School of Medicine / Faculty of Medicine, 2019, Physiology
  • Office for the Promotion of International Exchange, 2019, Medical Science A
  • Office for the Promotion of International Exchange, 2019, Medical Science B
  • Office for the Promotion of International Exchange, 2019, Forefront of Research at Kobe University B

Research at Kobe

  • 10 Oct. 2019, Illumination of abnormal neuronal activities caused by myelin impairment suggests possible contribution to learning deficits

Research Activities

Research Interests

  • 脳梗塞
  • ミクログリア
  • シナプス
  • 2光子励起顕微鏡
  • 神経-グリア相関
  • 生体

Research Areas

  • Life sciences / Clinical pharmacy
  • Life sciences / Physiology
  • Life sciences / Neuroscience - general
  • Life sciences / Neuroscience - general
  • Life sciences / Neuroscience - general

Awards

  • 2017 神戸大学, 神戸大学優秀若手研究賞・学長賞, 高次脳機能の解明と操作に光を当てる

    WAKE HIROAKI

    Others

Published Papers

  • Three-dimensional stimulation and imaging-based functional optical microscopy of biological cells

    Quan X, Kumar M, Matoba O, Awatsuji Y, Hayasaki Y, Hasegawa S, Wake Hiroaki

    Nov. 2018, Opt Lett, 43 (21), 5447 - 5450, English

    [Refereed]

    Scientific journal

  • Regulation of myelin structure and conduction velocity by perinodal astrocytes

    Dutta DJ, Woo DH, Lee PR, Pajevic S, Bukalo O, Huffman WC, Wake Hiroaki, Basser PJ, SheikhBahaei S, Lazarevic V, Smith JC, Fields RD

    Nov. 2018, Proc Natl Acad Sci U S A, 115 (46), 11832 - 11837, English

    [Refereed]

    Scientific journal

  • Akiko Takeda, Youichi Shinozaki, Kenji Kashiwagi, Nobuhiko Ohno, Kei Eto, Hiroaki Wake, Junichi Nabekura, Schuichi Koizumi

    Excitotoxicity is well known in the neuronal death in the brain and is also linked to neuronal damages in the retina. Recent accumulating evidence show that microglia greatly affect excitotoxicity in the brain, but their roles in retina have received only limited attention. Here, we report that retinal excitotoxicity is mediated by microglia. To this end, we employed three discrete methods, that is, pharmacological inhibition of microglia by minocycline, pharmacological ablation by an antagonist for colony stimulating factor 1 receptor (PLX5622), and genetic ablation of microglia using Iba1-tTA::DTAtetO/tetO mice. Intravitreal injection of NMDA increased the number of apoptotic retinal ganglion cells (RGCs) followed by reduction in the number of RGCs. Although microglia did not respond to NMDA directly, they became reactive earlier than RGC damages. Inhibition or ablation of microglia protected RGCs against NMDA. We found up-regulation of proinflammatory cytokine genes including Il1b, Il6 and Tnfa, among which Tnfa was selectively blocked by minocycline. PLX5622 also suppressed Tnfa expression. Tumor necrosis factor α (TNFα) signals were restricted in microglia at very early followed by spreading into other cell types. TNFα up-regulation in microglia and other cells were significantly attenuated by minocycline and PLX5622, suggesting a central role of microglia for TNFα induction. Both inhibition of TNFα and knockdown of TNF receptor type 1 by siRNA protected RGCs against NMDA. Taken together, our data demonstrate that a phenotypic change of microglia into a neurotoxic one is a critical event for the NMDA-induced degeneration of RGCs, suggesting an importance of non-cell-autonomous mechanism in the retinal neuronal excitotoxicity.

    Nov. 2018, Glia, 66 (11), 2366 - 2384, English, International magazine

    [Refereed]

    Scientific journal

  • Microglia Enhance Synapse Activity to Promote Local Network Synchronization

    Akiyoshi R, Wake Hiroaki, Kato D, Horiuchi H, Ono R, Ikegami A, Haruwaka K, Omori T, Tachibana Y, Moorhouse AJ, Nabekura J

    Oct. 2018, eNeuro, 5 (5), English

    [Refereed]

    Scientific journal

  • Tatsuya Ishikawa, Kei Eto, Sun Kwang Kim, Hiroaki Wake, Ikuko Takeda, Hiroshi Horiuchi, Andrew J Moorhouse, Hitoshi Ishibashi, Junichi Nabekura

    Peripheral nerve injury causes maladaptive plasticity in the central nervous system and induces chronic pain. In addition to the injured limb, abnormal pain sensation can appear in the limb contralateral to the injury, called mirror image pain. Because synaptic remodeling in the primary somatosensory cortex (S1) has critical roles in the induction of chronic pain, cortical reorganization in the S1 ipsilateral to the injured limb may also accompany mirror image pain. To elucidate this, we conducted in vivo 2-photon calcium imaging of neuron and astrocyte activity in the ipsilateral S1 after a peripheral nerve injury. We found that cross-callosal inputs enhanced the activity of both S1 astrocytes and inhibitory neurons, whereas activity of excitatory neurons decreased. When local inhibitory circuits were blocked, astrocyte-dependent spine plasticity and allodynia were revealed. Thus, we propose that cortical astrocytes prime the induction of spine plasticity and mirror image pain after peripheral nerve injury. Moreover, this result suggests that cortical synaptic rewiring could be sufficient to cause allodynia on the uninjured periphery.

    Aug. 2018, Pain, 159 (8), 1592 - 1606, English, International magazine

    [Refereed]

    Scientific journal

  • Three-dimensional stimulation and imaging-based functional optical microscopy of biological cells

    Xiangyu Quan, Manoj Kumar, MATOBA Osamu, Yasuhiro Awatsuji, Yoshio Hayasaki, Satoshi Hasegawa, WAKE Hiroki

    2018, Optics Letters, Vol. 43 (No. 21), pp. 5447 - 5480, English

    [Refereed]

    Scientific journal

  • Reduced Mastication Impairs Memory Function

    Fukushima-NakayamaY, OnoT, HayashiM, InoueM, Wake Hiroaki, OnoT, NakashimaT

    Aug. 2017, J Dent Res, 96 (9), 1058 - 1066, English

    [Refereed]

    Scientific journal

  • Akiko Miyamoto, Hiroaki Wake, Ayako Wendy Ishikawa, Kei Eto, Keisuke Shibata, Hideji Murakoshi, Schuichi Koizumi, Andrew J Moorhouse, Yumiko Yoshimura, Junichi Nabekura

    Microglia are the immune cells of the central nervous system that play important roles in brain pathologies. Microglia also help shape neuronal circuits during development, via phagocytosing weak synapses and regulating neurogenesis. Using in vivo multiphoton imaging of layer 2/3 pyramidal neurons in the developing somatosensory cortex, we demonstrate here that microglial contact with dendrites directly induces filopodia formation. This filopodia formation occurs only around postnatal day 8-10, a period of intense synaptogenesis and when microglia have an activated phenotype. Filopodia formation is preceded by contact-induced Ca(2+) transients and actin accumulation. Inhibition of microglia by genetic ablation decreases subsequent spine density, functional excitatory synapses and reduces the relative connectivity from layer 4 neurons. Our data provide the direct demonstration of microglial-induced spine formation and provide further insights into immune system regulation of neuronal circuit development, with potential implications for developmental disorders of immune and brain dysfunction.

    25 Aug. 2016, Nature communications, 7, 12540 - 12540, English, International magazine

    [Refereed]

    Scientific journal

  • Microglial Contact Prevents Excess Depolarization and Rescues Neurons from Excitotoxicity

    KatoG, InadaH, Wake Hiroaki, AkiyoshiR, Miyamoto Akiko, EtoK, IshikawaT, MoorhouseAJ, StrassmanAM, NabekuraJ

    Jun. 2016, eNeuro, 3 (3), English

    [Refereed]

    Scientific journal

  • Hiroaki Wake, Andrew J. Moorhouse, Akiko Miyamoto, Junichi Nabekura

    The traditional role of microglia has been in brain infection and disease, phagocytosing debris and secreting factors to modify disease progression. Recent evidence extends their role to healthy brain homeostasis, including the regulation of cell death, synapse elimination, neurogenesis, and neuronal surveillance. These actions contribute to the maturation and plasticity of neural circuits that ultimately shape behavior. Here we review microglial contributions to the development, plasticity, and maintenance of neural circuits with a focus on interactions with synapses. We introduce this topic by reviewing recent studies on the migration and proliferation of microglia within the brain, and conclude with the proposal that microglia dysfunction may adversely affect brain function, and thereby contribute to the development of psychiatric and neurological disorders.

    ELSEVIER SCIENCE LONDON, Apr. 2013, TRENDS IN NEUROSCIENCES, 36 (4), 209 - 217, English

    [Refereed]

  • Miyamoto A, Wake H, Moorhouse AJ, Nabekura J

    2013, Frontiers in cellular neuroscience, 7 (MAY)

    [Refereed]

  • Jacqueline Y. K. Leung, William R. Bennett, Rosalind P. Herbert, Adrian K. West, Philip R. Lee, Hiroaki Wake, R. Douglas Fields, Meng Inn Chuah, Roger S. Chung

    Prior studies have reported that metallothionein I/II (MT) promote regenerative axonal sprouting and neurite elongation of a variety of central nervous system neurons after injury. In this study, we evaluated whether MT is capable of modulating regenerative axon outgrowth of neurons from the peripheral nervous system. The effect of MT was firstly investigated in dorsal root ganglion (DRG) explants, where axons were scratch-injured in the presence or absence of exogenous MT. The application of MT led to a significant increase in regenerative sprouting of neurons 16 h after injury. We show that the pro-regenerative effect of MT involves an interaction with the low-density lipoprotein receptor megalin, which could be blocked using the competitive antagonist RAP. Pre-treatment with the mitogen-activated protein kinase (MAPK) inhibitor PD98059 also completely abrogated the effect of exogenous MT in promoting axonal outgrowth. Interestingly, we only observed megalin expression in neuronal soma and not axons in the DRG explants. To investigate this matter, an in vitro injury model was established using Campenot chambers, which allowed the application of MT selectively into either the axonal or cell body compartments after scratch injury was performed to axons. At 16 h after injury, regenerating axons were significantly longer only when exogenous MT was applied solely to the soma compartment, in accordance with the localized expression of megalin in neuronal cell bodies. This study provides a clear indication that MT promotes axonal regeneration of DRG neurons, via a megalin-and MAPK-dependent mechanism.

    SPRINGER BASEL AG, Mar. 2012, CELLULAR AND MOLECULAR LIFE SCIENCES, 69 (5), 809 - 817, English

    [Refereed]

    Scientific journal

  • Takanari Toyoda, Noriyuki Matsukawa, Takafumi Sagisaka, Norihiko Uematsu, Tetsuko Kanamori, Daisuke Kato, Masayuki Mizuno, Hiroaki Wake, Hideki Hida, Cesario V. Borlongan, Kosei Ojika

    Hippocampal cholinergic neurostimulating peptide (HCNP) is known to promote differentiation of septo-hippocampal cholinergic neurons. The HCNP precursor protein (HCNP-pp) may play several roles, for example, as an ATP-binding protein, a Raf kinase inhibitor protein, and a phosphatidylethanolamine-binding protein, as well as a precursor for HCNP. This study therefore aimed to elucidate the involvement of HCNP-pp in specific neural lineages after stroke using a hypoxic-ischemic (HI) rat model of brain ischemia. The specific neural lineages in the hippocampus were investigated 14 days after ischemia. Some bromodeoxyuridine (BrdU)(+) neural progenitor cells in the hippocampus of hypoxic, HI, or sham-operated rats expressed HCNP-pp. Almost half of the BrdU(+)/HCNP-pp(+) cells also expressed the oligodendrocyte lineage marker 2',3'-cyclic nucleotide 3'-phosphodiesterase, whereas only a few BrdU(+)/HCNP-pp(+) cells in the hippocampus in HI brains expressed the neuronal lineage marker, doublecortin (DCX). Interestingly, no BrdU(+)/HCNP-pp(+) progenitor cells in hypoxic, HI, or sham-operated brains expressed the astrocyte lineage marker, glial fibrillary acidic protein. Together with previous in vitro data, the results of this study suggest that the expression level of HCNP-pp regulates the differentiation of neural progenitor cells into specific neural lineages in the HI hippocampus, indicating that neural stem cell fate can be controlled via the HCNP-pp mediating pathway.

    COGNIZANT COMMUNICATION CORP, 2012, CELL TRANSPLANTATION, 21 (10), 2159 - 2169, English

    [Refereed]

    Scientific journal

  • Hiroyuki Inada, Miho Watanabe, Taku Uchida, Hitoshi Ishibashi, Hiroaki Wake, Tomomi Nemoto, Yuchio Yanagawa, Atsuo Fukuda, Junichi Nabekura

    Cortical GABAergic interneurons originate from ganglionic eminences and tangentially migrate into the cortical plate at early developmental stages. To elucidate the characteristics of this migration of GABAergic interneurons in living animals, we established an experimental design specialized for in vivo time-lapse imaging of the neocortex of neonate mice with two-photon laser-scanning microscopy. In vesicular GABA/glycine transporter (VGAT)-Venus transgenic mice from birth (P0) through P3, we observed multidirectional tangential migration of genetically-defined GABAergic interneurons in the neocortical marginal zone. The properties of this migration, such as the motility rate (distance/hr), the direction moved, and the proportion of migrating neurons to stationary neurons, did not change through P0 to P3, although the density of GABAergic neurons at the marginal zone decreased with age. Thus, the characteristics of the tangential motility of individual GABAergic neurons remained constant in development. Pharmacological block of GABA(A) receptors and of the Na(+)-K(+)-Cl(-) cotransporters, and chelating intracellular Ca(2+), all significantly reduced the motility rate in vivo. The motility rate and GABA content within the cortex of neonatal VGAT-Venus transgenic mice were significantly greater than those of GAD67-GFP knock-in mice, suggesting that extracellular GABA concentration could facilitate the multidirectional tangential migration. Indeed, diazepam applied to GAD67-GFP mice increased the motility rate substantially. In an in vitro neocortical slice preparation, we confirmed that GABA induced a NKCC sensitive depolarization of GABAergic interneurons in VGAT-Venus mice at P0-P3. Thus, activation of GABA(A)R by ambient GABA depolarizes GABAergic interneurons, leading to an acceleration of their multidirectional motility in vivo.

    PUBLIC LIBRARY SCIENCE, Dec. 2011, PLOS ONE, 6 (12), English

    [Refereed]

    Scientific journal

  • Marie-Eve Tremblay, Beth Stevens, Amanda Sierra, Hiroaki Wake, Alain Bessis, Axel Nimmerjahn

    Microglia were recently shown to play unexpected roles in normal brain development and adult physiology. This has begun to dramatically change our view of these resident "immune" cells. Here, we briefly review topics covered in our 2011 Society for Neuroscience minisymposium "The Role of Microglia in the Healthy Brain." This summary is not meant to be a comprehensive review of microglia physiology, but rather to share new results and stimulate further research into the cellular and molecular mechanisms by which microglia influence postnatal development, adult neuronal plasticity, and circuit function.

    SOC NEUROSCIENCE, Nov. 2011, JOURNAL OF NEUROSCIENCE, 31 (45), 16064 - 16069, English

    [Refereed]

    Scientific journal

  • Hiroaki Wake, Philip R. Lee, Douglas Fields

    Formation of myelin, the electrical insulation on axons produced by oligodendrocytes, is controlled by complex cell-cell signaling that regulates oligodendrocyte development and myelin formation on appropriate axons. If electrical activity could stimulate myelin induction, then neurodevelopment and the speed of information transmission through circuits could be modified by neural activity. We find that release of glutamate from synaptic vesicles along axons of mouse dorsal root ganglion neurons in culture promotes myelin induction by stimulating formation of cholesterol-rich signaling domains between oligodendrocytes and axons, and increasing local synthesis of the major protein in the myelin sheath, myelin basic protein, through Fyn kinase-dependent signaling. This axon-oligodendrocyte signaling would promote myelination of electrically active axons to regulate neural development and function according to environmental experience.

    AMER ASSOC ADVANCEMENT SCIENCE, Sep. 2011, SCIENCE, 333 (6049), 1647 - 1651, English

    [Refereed]

    Scientific journal

  • Masato Sawada, Naoko Kaneko, Hiroyuki Inada, Hiroaki Wake, Yasuko Kato, Yuchio Yanagawa, Kazuto Kobayashi, Tomomi Nemoto, Junichi Nabekura, Kazunobu Sawamoto

    Throughout life, new neurons are added and old ones eliminated in the adult mouse olfactory bulb. Previous studies suggested that olfactory experience controls the process by which new neurons are integrated into mature circuits. Here we report novel olfactory-experience-dependent mechanisms of neuronal turnover. Using two-photon laser-scanning microscopy and sensory manipulations in adult live mice, we found that the neuronal turnover was dynamically controlled by olfactory input in a neuronal subtype-specific manner. Olfactory input enhanced this turnover, which was characterized by the reiterated use of the same positions in the glomeruli by new neurons. Our results suggest that olfactory-experience-dependent modification of neuronal turnover confers structural plasticity and stability on the olfactory bulb.

    SOC NEUROSCIENCE, Aug. 2011, JOURNAL OF NEUROSCIENCE, 31 (32), 11587 - 11596, English

    [Refereed]

    Scientific journal

  • Kei Eto, Hiroaki Wake, Miho Watanabe, Hitoshi Ishibashi, Mami Noda, Yuchio Yanagawa, Junichi Nabekura

    Multiple cortical areas are involved in pain processing, including the primary somatosensory cortex (S1) and the anterior cingulate cortex (ACC). Although accumulations of evidence suggest that the S1 activity increases under chronic pain conditions, whether plastic change occurs or not within the S1, and whether and how the plastic change contributes to chronic pain behavior, is unknown. Here, we provide the first evidence that intra-regional remodeling within the mouse S1 accelerates chronic pain behavior by modulating neuronal activity in the ACC, one of the important cortical areas for chronic pain. Using two-photon Ca(2+) imaging, we found that the spontaneous activity of layer 2/3 neurons in the S1 and then response to sensory and layer 4 stimulations increased under chronic pain conditions. In addition, pharmacological attenuation and facilitation of S1 activity attenuated and facilitated the chronic pain behavior, respectively. Furthermore, electrical response of the ACC to peripheral stimulation successfully correlated with S1 neuronal activity, and inhibition of ACC activity alleviated the mechanical allodynia. The present results will provide development of efficient therapeutic strategies against chronic pain by focusing on the S1 and ACC.

    21, 25 May 2011, The Journal of neuroscience : the official journal of the Society for Neuroscience, 31 (21), 7631 - 6, English, International magazine

    [Refereed]

  • Hiroaki Wake, R. Douglas Fields

    Broad interest in the rapidly advancing field of microglial involvement in forming neural circuits is evident from the fresh findings published in leading journals. This special issue of Neuron Glia Biology contains a special collection of research articles and reviews concerning the new appreciation of microglial function in the normal physiology of the brain that extends beyond their traditionally understood role in pathology.

    CAMBRIDGE UNIV PRESS, 2011, NEURON GLIA BIOLOGY, 7 (1), 1 - 3, English

    [Refereed]

    Scientific journal

  • Hiroaki Wake, Andrew J. Moorhouse, Junichi Nabekura

    Microglia cells are the immune cells of the central nervous system and consequently play important roles in brain infections and inflammation. Recent in vivo imaging studies have revealed that in the resting healthy brain, microglia are highly dynamic, moving constantly to actively survey the brain parenchyma. These active microglia can rapidly respond to pathological insults, becoming activated to induce a range of effects that may contribute to both pathogenesis, or to confer neuronal protection. However, interactions between microglia and neurons are being recognized as important in shaping neural circuit activity under more normal, physiological conditions. During development and neurogenesis, microglia interactions with neurons help to shape the final patterns of neural circuits important for behavior and with implications for diseases. In the mature brain, microglia can respond to changes in sensory activity and can influence neuronal activity acutely and over the long term. Microglia seem to be particularly involved in monitoring the integrity of synaptic function. In this review, we discuss some of these new insights into the involvement of microglia in neural circuits.

    CAMBRIDGE UNIV PRESS, 2011, NEURON GLIA BIOLOGY, 7 (1), 47 - 53, English

    [Refereed]

    Scientific journal

  • Toshiyuki Marumo, Kei Eto, Hiroaki Wake, Tomohiro Omura, Junichi Nabekura

    BACKGROUND AND PURPOSE: 20-Hydroxyeicosatetraenoic acid is a potent vasoconstrictor that contributes to cerebral ischaemia. An inhibitor of 20-Hydroxyeicosatetraenoic acid synthesis, TS-011, reduces infarct volume and improves neurological deficits in animal stroke models. However, little is known about how TS-011 affects the microvessels in ischaemic brain. Here, we investigated the effect of TS-011 on microvessels after cerebral ischaemia. EXPERIMENTAL APPROACH: TS-011 (0.3 mg·kg(-1) ) or a vehicle was infused intravenously for 1 h every 6 h in a mouse model of stroke, induced by transient occlusion of the middle cerebral artery occlusion following photothrombosis. The cerebral blood flow velocity and the vascular perfusion area of the peri-infarct microvessels were measured using in vivo two-photon imaging. KEY RESULTS: The cerebral blood flow velocities in the peri-infarct microvessels decreased at 1 and 7 h after reperfusion, followed by an increase at 24 h after reperfusion in the vehicle-treated mice. We found that TS-011 significantly inhibited both the decrease and the increase in the blood flow velocities in the peri-infarct microvessels seen in the vehicle-treated mice after reperfusion. In addition, TS-011 significantly inhibited the reduction in the microvascular perfusion area after reperfusion, compared with the vehicle-treated group. Moreover, TS-011 significantly reduced the infarct volume by 40% at 72 h after middle cerebral artery occlusion. CONCLUSIONS AND IMPLICATIONS: These findings demonstrated that infusion of TS-011 improved defects in the autoregulation of peri-infarct microcirculation and reduced the infarct volume. Our results could be relevant to the treatment of cerebral ischaemia.

    6, Nov. 2010, British journal of pharmacology, 161 (6), 1391 - 402, English, International magazine

    [Refereed]

  • Takafumi Sagisaka, Noriyuki Matsukawa, Takanari Toyoda, Norihiko Uematsu, Tetsuko Kanamori, Hiroaki Wake, Cesario V. Borlongan, Kosei Ojika

    Hippocampal cholinergic neurostimulating peptide (HCNP), originally purified from young rat hippocampus, has been known to promote the differentiation of septo-hippocampal cholinergic neurons. Recently, the precursor protein of HCNP (HCNP-pp) has also received attention as a multifunctional protein with roles, in addition to serving as the HCNP precursor, such as acting as an ATP-binding protein, a Raf kinase inhibitor protein (RKIP), and phosphatidylethanolamine-binding protein (PEBP). In particular, the function of RKIP has attracted attention over several years for its role in controlling cellular proliferation and metastasis in cancer cells. HCNP-pp is also thought to be important in regulating the proliferation and differentiation of neuronal cells in vitro and in vivo by modification of the MAPK cascade. In the present study, we used cultured adult rat hippocampal progenitor cells (AHPs), which are thought to be important for memory formation, and focused on the role of HCNP-pp in adult neurogenesis, namely, the production of new neurons from neural stem/progenitor cells. We found that HCNP-pp expression in AHPs was closely associated with differentiation into MAP2ab-positive neurons and RIP-positive oligodendrocytes, but not into GFAP-positive astrocytes. By contrast, a down-regulated HCNP-pp expression in AHPs accompanied differentiation into GFAP-positive astrocytes. Direct manipulations of HCNP-pp via viral over-expression or siRNA downregulation further confirmed the HCNP-pp contribution to specific neural lineage commitment of AHPs. Our results show that the expression level of HCNP-pp acts as a key regulator for differentiation of cultured AHPs into specific neural lineages, indicating that the control of neural stem cell fate can be achieved via the HCNP-pp pathway. (C) 2010 Elsevier B.V. All rights reserved.

    ELSEVIER SCIENCE BV, Apr. 2010, BRAIN RESEARCH, 1327, 107 - 117, English

    [Refereed]

    Scientific journal

  • Miho Watanabe, Hiroaki Wake, Andrew J. Moorhouse, Junichi Nabekura

    The neuronal K+-Cl- cotransporter (KCC2) is a membrane transport protein that extrudes Cl- from neurons and helps maintain low intracellular [Cl-] and hyperpolarizing GABAergic synaptic potentials. Depolarizing gamma-aminobutyric acid (GABA) responses in neonatal neurons and following various forms of neuronal injury are associated with reduced levels of KCC2 expression. Despite the importance for plasticity of inhibitory transmission, less is known about cellular mechanisms involved in more dynamic changes in KCC2 function. In this study, we investigated the role of tyrosine phosphorylation in KCC2 localization and function in hippocampal neurons and in cultured GT1-7 cells. Mutation to the putative tyrosine phosphorylation site within the long intracellular carboxyl terminus of KCC2(Y1087D) or application of the tyrosine kinase inhibitor genistein shifted the GABA reversal potential (E-GABA) to more depolarized values, indicating reduced KCC2 function. This was associated with a change in the expression pattern of KCC2 from a punctate distribution to a more uniform distribution, suggesting that functional tyrosine-phosphorylated KCC2 forms clusters in restricted membrane domains. Sodium vanadate, a tyrosine phosphatase inhibitor, increased the proportion of KCC2 associated with lipid rafts membrane domains. Loss of tyrosine phosphorylation also reduced oligomerization of KCC2. A loss of the punctuate distribution and oligomerization of KCC2 and a more depolarized E-GABA Were seen when the 28-amino-acid carboxyl terminus of KCC2 was deleted. These results indicate that direct tyrosine phosphorylation of KCC2 results in membrane clusters and functional transport activity, suggesting a mechanism by which intracellular Cl- concentrations and GABA responses can be rapidly modulated.

    AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, Oct. 2009, JOURNAL OF BIOLOGICAL CHEMISTRY, 284 (41), 27980 - 27988, English

    [Refereed]

    Scientific journal

  • Hiroaki Wake, Andrew J. Moorhouse, Shozo Jinno, Shinichi Kohsaka, Junichi Nabekura

    Recent studies have identified the important contribution of glial cells to the plasticity of neuronal circuits. Resting microglia, the primary immune effector cells in the brain, dynamically extend and retract their processes as if actively surveying the microenvironment. However, just what is being sampled by these resting microglial processes has not been demonstrated in vivo, and the nature and function of any interactions between microglia and neuronal circuits is incompletely understood. Using in vivo two-photon imaging of fluorescent-labeled neurons and microglia, we demonstrate that the resting microglial processesmakebrief (similar to 5 min) and direct contacts with neuronal synapses at a frequency of about once per hour. These contacts are activity-dependent, being reduced in frequency by reductions in neuronal activity. After transient cerebral ischemia, the duration of these microglia-synapse contacts are markedly prolonged (similar to 1 h) and are frequently followed by the disappearance of the presynaptic bouton. Our results demonstrate that at least part of the dynamic motility of resting microglial processes in vivo is directed toward synapses and propose that microglia vigilantly monitor and respond to the functional status of synapses. Furthermore, the striking finding that some synapses in the ischemic areas disappear after prolonged microglial contact suggests microglia contribute to the subsequent increased turnover of synaptic connections. Further understanding of the mechanisms involved in the microglial detection of the functional state of synapses, and of their role in remodeling neuronal circuits disrupted by ischemia, may lead to novel therapies for treating brain injury that target microglia.

    SOC NEUROSCIENCE, Apr. 2009, JOURNAL OF NEUROSCIENCE, 29 (13), 3974 - 3980, English

    [Refereed]

    Scientific journal

  • Koichiro Iohara, Li Zheng, Hiroaki Wake, Masataka Ito, Junichi Nabekura, Hideaki Wakita, Hiroshi Nakamura, Takeshi Into, Kenji Matsushita, Misako Nakashima

    Cell therapy with stem cells and endothelial progenitor cells (EPCs) to stimulate vasculogenesis as a potential treatment for ischemic disease is an exciting area of research in regenerative medicine. EPCs are present in bone marrow, peripheral blood, and adipose tissue. Autologous EPCs, however, are obtained by invasive biopsy, a potentially painful procedure. An alternative approach is proposed in this investigation. Permanent and deciduous pulp tissue is easily available from teeth after extraction without ethical issues and has potential for clinical use. We isolated a highly vasculogenic subfraction of side population (SP) cells based on CD31 and CD146, from dental pulp. The CD31(-); CD146(-) SP cells, demonstrating CD34(+) and vascular endothelial growth factor-2 (VEGFR2)/Flk1(+), were similar to EPCs. These cells were distinct from the hematopoietic lineage as CD11b, CD14, and CD45 mRNA were not expressed. They showed high proliferation and migration activities and multilineage differentiation potential including vasculogenic potential. In models of mouse hind limb ischemia, local transplantation of this subfraction of SP cells resulted in successful engraftment and an increase in the blood flow including high density of capillary formation. The transplanted cells were in proximity of the newly formed vasculature and expressed several proangiogenic factors, such as VEGF-A, G-CSF, GM-CSF, and MMP3. Conditioned medium from this subfraction showed the mitogenic and antiapoptotic activity on human umbilical vein endothelial cells. In conclusion, subfraction of SP cells from dental pulp is a new stem cell source for cell-based therapy to stimulate angiogenesis/vasculogenesis during tissue regeneration.

    ALPHAMED PRESS, Sep. 2008, STEM CELLS, 26 (9), 2408 - 2418, English

    [Refereed]

    Scientific journal

  • Hiroaki Wake, Miho Watanabe, Andrew J. Moorhouse, Takashi Kanematsu, Shoko Horibe, Noriyuki Matsukawa, Kiyofumi Asai, Kosei Ojika, Masato Hirata, Junichi Nabekura

    The K+ Cl- cotransporter KCC2 plays an important role in chloride homeostasis and in neuronal responses mediated by ionotropic GABA and glycine receptors. The expression levels of KCC2 in neurons determine whether neurotransmitter responses are inhibitory or excitatory. KCC2 expression is decreased in developing neurons, as well as in response to various models of neuronal injury and epilepsy. We investigated whether there is also direct modulation of KCC2 activity by changes in phosphorylation during such neuronal stressors. We examined tyrosine phosphorylation of KCC2 in rat hippocampal neurons under different conditions of in vitro neuronal stress and the functional consequences of changes in tyrosine phosphorylation. Oxidative stress (H2O2) and the induction of seizure activity (BDNF) and hyperexcitability (0 Mg2+) resulted in a rapid dephosphorylation of KCC2 that preceded the decreases in KCC2 protein or mRNA expression. Dephosphorylation of KCC2 is correlated with a reduction of transport activity and a decrease in [Cl-](i), as well as a reduction in KCC2 surface expression. Manipulation of KCC2 tyrosine phosphorylation resulted in altered neuronal viability in response to in vitro oxidative stress. During continued neuronal stress, a second phase of functional KCC2 downregulation occurs that corresponds to decreases in KCC2 protein expression levels. We propose that neuronal stress induces a rapid loss of tyrosine phosphorylation of KCC2 that results in translocation of the protein and functional loss of transport activity. Additional understanding of the mechanisms involved may provide means for manipulating the extent of irreversible injury resulting from different neuronal stressors.

    SOC NEUROSCIENCE, Feb. 2007, JOURNAL OF NEUROSCIENCE, 27 (7), 1642 - 1650, English

    [Refereed]

    Scientific journal

  • Yoshito Mizoguchi, Akihiko Kitamura, Hiroaki Wake, Hitoshi Ishibashi, Miho Watanabe, Takuya Nishimaki, Junichi Nabekura

    During the development of the rat hippocampus, both gamma-aminobutyric acid (GABA)(B) autoreceptors and brain-derived neurotrophic factor (BDNF) play important roles in the formation of GABAergic synapses as well as in the GABA(A) receptor-mediated transmissions. While a number of studies have reported rapid effects of BDNF on GABA(A) receptor-mediated responses, the interactions between GABA(B) autoreceptors and BDNF are less clear. Using conventional whole-cell patch-clamp recordings, we demonstrated here that BDNF significantly occludes baclofen-induced suppression of GABA(A) receptor-mediated transmissions in each of the preparations including hippocampal slices prepared from P14 rats, hippocampal CA1 pyramidal neurons isolated from P14 and P21 rats, and cultured hippocampal pyramidal neurons. This effect of BDNF was rapid and reversible, and was mediated via the activation of presynaptic TrkB receptor tyrosine kinases, and subsequent activation of phospholipase C and protein kinase C. On the contrary, in hippocampal CA1 pyramidal neurons isolated from P7 rats, BDNF failed to occlude the GABA(B) receptor-mediated inhibition of GABA release. Thus, the ability of BDNF to occlude the GABA(B) receptor-mediated inhibition of GABA release develops between P7 and P14. This demonstrates a novel aspect of the effects of BDNF on inhibitory transmissions in rat hippocampus, which may have some functional roles in the induction of developmental plasticity and/or pathophysiology of epilepsy.

    BLACKWELL PUBLISHING, Oct. 2006, EUROPEAN JOURNAL OF NEUROSCIENCE, 24 (8), 2135 - 2144, English

    [Refereed]

    Scientific journal

MISC

Presentations

  • The response to whisker stimulation in the visual cortex of monocular deprived mice in vivo

    橋本 明香里, MIYAMOTO AKIKO, TACHIBANA YOSHIHISA, 春若航一路, WAKE HIROAKI

    9th FAOPS, Mar. 2019, English, 神戸, International conference

    Poster presentation

  • Physiologiacl function of microglia and their effect on neuronal circuits

    Hiroaki Wake

    第9回アジアオセアニア生理学会(神戸市), Mar. 2019, English, 神戸, International conference

    Public symposium

  • 生体 in Vivoイメージング

    WAKE HIROAKI

    第2回ニコンイメージングフォーラム, Feb. 2019, Japanese, 東京, Domestic conference

    Nominated symposium

  • ミクログリアの新規生理機能の可視化

    WAKE HIROAKI

    北海道大学医学部免疫代謝内科学セミナー, Feb. 2019, Japanese, 札幌, Domestic conference

    Public discourse

  • ミクログリアの新規生理機能とその破綻による病態の表出

    WAKE HIROAKI

    第11回先端脳科学セミナー, Feb. 2019, Japanese, 中央, Domestic conference

    Oral presentation

  • High Temporal and Spatial Pattern Stimulation to Manipulate Brain Function

    Hiroaki Wake

    International Workshop on Bioimaging2019, Feb. 2019, English, 宇都宮, International conference

    [Invited]

    Invited oral presentation

  • High Temporal and Spatial Pattern Stimulation to Manipulate Brain Function

    Hiroaki Wake

    ABiS International Symposium, Feb. 2019, Japanese, 岡崎, International conference

    Oral presentation

  • 全身炎症時におけるミクログリアによる血液脳関門の制御

    春若航一路, WAKE HIROAKI

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

    Oral presentation

  • 全身炎症時におけるミクログリアによる血液脳関門の制御

    春若航一路, WAKE HIROAKI

    第6回先進イメージング医学研究会・学術集会, Jan. 2019, Japanese, 神戸, Domestic conference

    Oral presentation

  • 光による高次脳機能の計測と操作を目指して

    WAKE HIROAKI

    レーザー学会第39回年次大会, Jan. 2019, Japanese, 東京, Domestic conference

    Invited oral presentation

  • ミクログリアによる神経機能修飾

    WAKE HIROAKI

    Neurovascular Unit研究会2019, Jan. 2019, Japanese, 東京, Domestic conference

    Oral presentation

  • オリゴデンドロサイトおよびその前駆細胞のin vivo カルシウムイメージング

    尾野 里穂, SUGIO SHOUTA, TACHIBANA YOSHIHISA, WAKE HIROAKI

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

    Oral presentation

  • 2光子励起を用いたホログラフィック光刺激法の開発:現状と展望

    SUGIO SHOUTA, TACHIBANA YOSHIHISA, WAKE HIROAKI

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

    Oral presentation

  • 中枢神経系免疫細胞ミクログリアの新規生理機能とその病態への関与

    WAKE HIROAKI

    日本薬学会北陸支部特別講演会, Dec. 2018, Japanese, 金沢, Domestic conference

    Public discourse

  • Physiclogocal function of microglia and their role for disease formation

    WAKE HIROAKI

    武田薬品社内シンポジウム, Dec. 2018, Japanese, 藤沢, Domestic conference

    Public discourse

  • Microglia in physiological brain—Focusing on microglia—synapse interactions

    Hiroaki Wake

    Cold Spring Harbor Asia Conferences, Dec. 2018, English, 蘇州, International conference

    [Invited]

    Invited oral presentation

  • Change of lipid profile in myelin associated with motor learning affect on neuronal activity pattern in primary motor cortex.

    Kazuki Nishida, Yoshihisa Tachibana, Shumpei Sato, Fumiyoshi Yamazaki, Mitsutoshi Setou, Hiroaki Wake

    第23 回グリア研究会, Dec. 2018, Japanese, 名古屋, Domestic conference

    Oral presentation

  • Ca2+ imaging of oligodendrocyte and oligodendrocyte precursor cell in vivo

    Shouta Sugio, Riho Ono, Yoshihisa Tachibana, Hiroaki Wake

    次世代脳プロジェクト 冬のシンポジウム, Dec. 2018, English, 東京, Domestic conference

    Poster presentation

  • 2光子励起を用いたホログラフィック光刺激の現状:生体試料への適用を目指して

    SUGIO SHOUTA, TACHIBANA YOSHIHISA, WAKE HIROAKI

    CREST第2回シンポジウム, Dec. 2018, Japanese, 西尾, Domestic conference

    Oral presentation

  • 大脳皮質感覚野の生体イメージングによる疼痛発症機構解明へのアプローチ

    岡田 卓也, TACHIBANA YOSHIHISA, NOMURA YUKI, OBATA NORIHIKO, MIZOBUCHI SATOSHI, WAKE HIROAKI

    第111回 近畿生理学談話会, Nov. 2018, Japanese, 和歌山, Domestic conference

    Oral presentation

  • 運動学習と関連した白質における脂質の変化が一次運動野の神経活動に及ぼす影響

    西田 一貴, TACHIBANA YOSHIHISA, 佐藤 駿平, 山崎 文義, 瀬藤 光利, WAKE HIROAKI

    第111回 近畿生理学談話会, Nov. 2018, Japanese, 和歌山, Domestic conference

    Oral presentation

  • ホログラフィック光照射による蛍光励起の強度均一化"

    小管啓仁, Xiangyu Quan, MATOBA Osamu, 早崎芳夫, 粟辻安浩, WAKE Hiroaki

    日本光学会年次学術講演会(Optics & Photonics Japan 2018), Nov. 2018, Japanese, 筑波大学東京キャンパス文京校舎,東京, Domestic conference

    Oral presentation

  • グリア細胞の生理機能と神経回路機能

    WAKE HIROAKI

    第48回小児神経セミナー, Nov. 2018, Japanese, 大阪, Domestic conference

    Invited oral presentation

  • The scrap and build of oligodendrocyte function and myelin components

    WAKE HIROAKI

    スクラップ&ビルド領域会議, Nov. 2018, Japanese, 大阪, Domestic conference

    Oral presentation

  • Multimodal Digital Holographic Microscopy

    Xiangyu Quan, Manoj Kumar, MATOBA Osamu, Yasuhiro Awatsuji, Yoshio Hayasaki, Satoshi Hasegawa, WAKE Hiroaki, Mitsuhiro Morita

    The 8th Japana-Korea workshop on digital holography and information photonics (DHIP 2018), Nov. 2018, English, DHIP2018, Osaka; Japan, International conference

    [Invited]

    Invited oral presentation

  • In vivo tracing of single neuron activity with Ca2+ imaging of primary somatosensory cortex in mouse models of postoperative pain and inflammatory pain

    Takuya Okada, Yoshihisa Tachibana, Yuki Nomura, Norihiko Obata, Satoshi Mizobuchi, Hiroaki Wake

    Neuroscience 2018, Nov. 2018, English, San Diego, CA, International conference

    Poster presentation

  • Ca2+ imaging of oligodendrocyte and oligodendrocyte precursor cell in vivo

    Riho Ono, Shouta Sugio, Yoshihisa Tachibana, Hiroaki Wake

    新学術領域研究 スクラップ&ビルドによる脳機能の動的制御 第3回領域会議, Nov. 2018, Japanese, 大阪, Domestic conference

    Poster presentation

  • A New Type of Microscopy for Light Stimulation and 3D Imaging;

    Xiangyu Quan, Manoj Kumar, MATOBA Osamu, Yasuhiro Awatsuji, Yoshio Hayasaki, Satoshi Hasegawa, WAKE Hiroaki, Mitsuhiro Morita

    International Workshop on Holography and Related Technologies 2018 (IWH2018), Nov. 2018, English, IWH2018, Suzhou; China;, International conference

    [Invited]

    Invited oral presentation

  • 脳科学について

    WAKE HIROAKI

    santec社内講演会, Oct. 2018, Japanese, 小牧, Domestic conference

    Public discourse

  • ミクログリアの生理機能とその破綻による疾患について

    WAKE HIROAKI

    東京女子医科大セミナー, Oct. 2018, Japanese, 東京, Domestic conference

    Public discourse

  • ミクログリアの生理・病態を踏まえた認知症治療戦略

    WAKE HIROAKI

    第37回日本認知症学会学術集会, Oct. 2018, Japanese, 札幌, Domestic conference

    [Invited]

    Nominated symposium

  • Visualization and manipulation of glial cell functions in vivo

    Hiroaki Wake

    glial heterogeneity SPP1757, Oct. 2018, English, シュパイヤー, International conference

    Oral presentation

  • Two-photon in vivo imaging of oligodendrocyte Ca2+ activity in mice

    Riho Ono, Shouta Sugio, Yoshihisa Tachibana, Hiroaki Wake

    Young glia, Oct. 2018, English, シュパイヤー, International conference

    Poster presentation

  • 単眼遮蔽による視覚野のヒゲ刺激への応答変化のin vivoイメージング

    橋本 明香里, MIYAMOTO AKIKO, TACHIBANA YOSHIHISA, 春若航一路, WAKE HIROAKI

    関西5医科大学コンソーシアム合宿, Sep. 2018, Japanese, 大阪, Domestic conference

    Poster presentation

  • 生体イメージング最前線

    WAKE HIROAKI

    小野薬品工業「脳移転治療について考える会」, Sep. 2018, Japanese, 京都, Domestic conference

    Public discourse

  • Neurochemistry of neuron-glia interaction

    Hiroaki Wake

    WFSBP2018 The ISN-JSN, Sep. 2018, English, 神戸, International conference

    [Invited]

    Nominated symposium

  • Microglia in Health and Disease.- Interaction with synapses-

    Hiroaki Wake

    日本生化学大会, Sep. 2018, Japanese, 京都, Domestic conference

    [Invited]

    Invited oral presentation

  • Microglia and Synapses

    Hiroaki Wake

    ICN2018 世界神経病理学会, Sep. 2018, English, 東京, International conference

    [Invited]

    Nominated symposium

  • In vivo tracing of single neuron activity with Ca2+ imaging of primary somatosensory cortex in mouse models of postoperative pain and inflammatory pain

    岡田 卓也, 橘 吉寿, NOMURA YUKI, OBATA NORIHIKO, MIZOBUCHI SATOSHI, WAKE HIROAKI

    Cold Spring Harbor Asia Confference, Sep. 2018, English, 淡路, International conference

    Poster presentation

  • What we see in microglia about schizophrenia

    池上暁湖, 春若航一路, TACHIBANA YOSHIHISA, WAKE HIROAKI

    第5回先進イメージング医学研究会, Aug. 2018, Japanese, 京都, Domestic conference

    Oral presentation

  • 単眼遮蔽による、高次視覚野のヒゲ刺激への応答変化のin vivo イメージング

    橋本 明香里, MIYAMOTO AKIKO, TACHIBANA YOSHIHISA, 春若航一路, WAKE HIROAKI

    第41回日本神経科学大会, Jul. 2018, English, 神戸, Domestic conference

    Poster presentation

  • 術後痛モデルマウスにおける第一次体性感覚野のin vivoカルシウムイメージング

    岡田 卓也, TACHIBANA YOSHIHISA, NOMURA YUKI, OBATA NORIHIKO, MIZOBUCHI SATOSHI, WAKE HIROAKI

    第41回日本神経科学大会, Jul. 2018, English, 神戸, Domestic conference

    Poster presentation

  • 術後痛モデルマウスにおける第一次体性感覚野 in vivo カルシウムイメージング

    岡田 卓也, 橘 吉寿, NOMURA YUKI, OBATA NORIHIKO, MIZOBUCHI SATOSHI, WAKE HIROAKI

    第5回イメージング数理研究会, Jul. 2018, Japanese, 神戸, Domestic conference

    Poster presentation

  • 術後痛モデルマウスにおける第一次体性感覚野 in vivo カルシウムイメージング

    岡田 卓也, 橘 吉寿, NOMURA YUKI, OBATA NORIHIKO, MIZOBUCHI SATOSHI, WAKE HIROAKI

    第41回日本神経科学大会, Jul. 2018, Japanese, 神戸, Domestic conference

    Poster presentation

  • 高精度時空間分解能を持つ光による脳機能計測・操作を目指して

    WAKE HIROAKI

    イメージング数理研究会, Jul. 2018, Japanese, 神戸, Domestic conference

    Oral presentation

  • Microglia in health and disease -lesson from schizophreniamodel mice

    WAKE HIROAKI

    第41回日本神経科学大会, Jul. 2018, Japanese, 神戸, Domestic conference

    [Invited]

    Nominated symposium

  • グリアの生理機能とその破綻による精神疾患の可能性

    WAKE HIROAKI

    動的恒常性研究会, Jun. 2018, Japanese, 東京, Domestic conference

    Oral presentation

  • Fetal microglia changes by maternal immune activation

    Kana Ozaki, Wake Hiroaki, Hideto Yamada

    第70回日本産科婦人科学会学術講演会, May 2018, English, 仙台, Domestic conference

    Public symposium

  • High Temporal and Spatial Pattern Stimulation to Manipulate Brain Function

    Hiroaki Wake, Koichiro Haruwaka, Xiangyu Quan, Osamu Matoba

    OPIC2018, Apr. 2018, English, 横浜, International conference

    Oral presentation

  • High Temporal and Spatial Pattern Stimulation to Manipulate Brain Function

    WAKE Hiroaki, Koichiro Haruwaka, Xiangyu Quan, MATOBA Osamu

    BISC, Apr. 2018, English, OPIC2018, 神奈川、横浜, International conference

    Oral presentation

  • Microglia sense systemic immune status to modify activity of neuronal circuit

    Koichiro Haruwaka, Junichi Nabekura, Wake Hiroaki

    第95回日本生理学会大会, Mar. 2018, Japanese, 日本生理学会大会, 香川, Domestic conference

    Oral presentation

  • Abnormal Behavior and Malformation of Microglia in Schizophrenic Mice

    Ako Ikegami, Koichiro Haruwaka, Wake Hiroaki

    第2回神戸大学・ワシントン大学・オスロ大学国際合同シンポジウム, Mar. 2018, English, 神戸大学・ワシントン大学・オスロ大学国際合同シンポジウム, ハワイ, 米国, International conference

    Poster presentation

  • 生体イメージングが明らかにする脳-免疫系の相互作用

    春若 航一路, 鍋倉 淳一, Wake Hiroaki

    岡崎信用金庫先端奨学金制度 成果発表会, Feb. 2018, Japanese, 岡崎信用金庫先端奨学金制度 成果発表会, 愛知, Domestic conference

    Oral presentation

  • Optical control of neuron and glial cells by the 3D multi-points stimulation

    春若 航一路, 全 香玉, 森田 光洋, Miyamoto Akiko, 的場 修, Wake Hiroaki

    CREST「光の特性を活用した生命機能の時空間制御技術の開発と応用」研究領域 第2回領域会議, Jan. 2018, Japanese, CREST「光の特性を活用した生命機能の時空間制御技術の開発と応用」研究領域 第2回領域会議, 東京, Domestic conference

    Poster presentation

  • 統合失調症モデルマウスにおけるミクログリア動態・形態の変容

    Ako Ikegami, Koichiro Haruwaka, Wake Hiroaki

    次世代脳冬のシンポジウム, Dec. 2017, Japanese, 次世代脳冬のシンポジウム, 東京, Domestic conference

    Poster presentation

  • 統合失調症モデルマウスにおけるミクログリア動態・形態の変容

    Ako Ikegami, Koichiro Haruwaka, Wake Hiroaki

    第7回ニューロサイエンス研究会, Dec. 2017, Japanese, ニューロサイエンス研究会, 兵庫, Domestic conference

    Oral presentation

  • 髄鞘のスクラップアンドビルドによる脳情報処理の効率化

    Wake Hiroaki

    次世代脳冬のシンポジウム, Dec. 2017, Japanese, 次世代脳冬のシンポジウム, 東京, Domestic conference

    Oral presentation

  • Microglia sense systemic immune activation in autoimmune disease model.

    Koichiro Haruwaka, Junichi Nabekura, Wake Hiroaki

    次世代脳冬のシンポジウム, Dec. 2017, Japanese, 次世代脳冬のシンポジウム, 東京, Domestic conference

    Poster presentation

  • 統合失調症モデルマウスにおけるミクログリア動態・形態の変容

    Ako Ikegami, Koichiro Haruwaka, Wake Hiroaki

    第110回近畿生理学談話会, Nov. 2017, Japanese, 近畿生理学談話会, 兵庫, Domestic conference

    Oral presentation

  • 自己免疫疾患におけるミクログリアの変化

    春若 航一路, 鍋倉 淳一, Wake Hiroaki

    第111回近畿生理学談話会, Nov. 2017, Japanese, 近畿生理学談話会, 兵庫, Domestic conference

    Oral presentation

  • 高次脳機能に関わる中枢神経系免疫細胞の生理機能

    Wake Hiroaki

    東京大学大学院医学研究科, Nov. 2017, Japanese, 東京大学大学院医学研究科, 東京, Domestic conference

    [Invited]

    Invited oral presentation

  • 髄鞘制御不全による情報処理異常の可視化

    Wake Hiroaki

    神経組織培養研究会, Oct. 2017, Japanese, 神経組織培養研究会, 愛知, Domestic conference

    [Invited]

    Invited oral presentation

  • 光で迫る脳免疫細胞の機能について

    Wake Hiroaki

    第49回藤田学園医学会シンポジウム(愛知県豊名市), Oct. 2017, Japanese, 藤田学園医学会シンポジウム, 愛知, Domestic conference

    [Invited]

    Invited oral presentation

  • 光で照らし出すグリアの新機能および脳機能への寄与

    Wake Hiroaki

    (株)ファイザー 第12回緑内障若手研究者の会(東京), Oct. 2017, Japanese, (株)ファイザー 緑内障若手研究者の会, 東京, Domestic conference

    [Invited]

    Invited oral presentation

  • Microglia sense systemic immune status to modify activity of neuronal circuit

    Koichiro Haruwaka, Wake Hiroaki, Junichi Nabekura

    Life Science Retreat 2017, Oct. 2017, English, Life Science Retreat 2017, 山梨, Domestic conference

    Poster presentation

  • Physiology of microglia -New Insights-

    Wake Hiroaki

    Physiology of microglia XXIII World Congres of Neurology, Sep. 2017, English, Physiology of microglia XXIII World Congres of Neurology, 京都, International conference

    [Invited]

    Nominated symposium

  • Physiology of microglia

    Wake Hiroaki

    九州大学歯学部, Sep. 2017, English, 九州大学歯学部, 福岡, Domestic conference

    [Invited]

    Invited oral presentation

  • Myelination for information processing

    Wake Hiroaki

    第90回日本神経化学会大会, Sep. 2017, English, 日本神経化学会大会, 仙台, Domestic conference

    Oral presentation

  • Microglial contribute to dendritic spine formation in postnatal mice somatosensory cortex

    Miyamoto Akiko, Wake Hiroaki, Ayako Ishikawa, Hideji Murakoshi, Kei Eto, Yumiko Yoshimura, Junichi Nabekura

    日本神経化学学会, Sep. 2017, English, 日本神経化学学会, 仙台, Domestic conference

    [Invited]

    Nominated symposium

  • 2光子顕微鏡による生体イメージング

    Wake Hiroaki

    京都大学呼吸器内科, Sep. 2017, Japanese, 京都大学呼吸器内科, 京都, Domestic conference

    Oral presentation

  • 統合失調症モデルマウスにおけるミクログリア動態・形態の変容

    Ako Ikegami, Koichiro Haruwaka, Wake Hiroaki

    新学術領域 S&B第2回班会議, Aug. 2017, Japanese, 新学術領域 S&B班会議, 山梨, Domestic conference

    Poster presentation

  • 高精度時空間分解能を持つ光刺激法による脳機能操作

    Wake Hiroaki

    第14回生体イメージング研究会, Aug. 2017, Japanese, 生体イメージング研究会, 京都, Domestic conference

    Oral presentation

  • oligodendrocyte and myelin remodeking in information processing

    Wake Hiroaki

    第2回「スクラップビルド」領域会議, Aug. 2017, English, 新学術領域 S&B班会議, 山梨, Domestic conference

    Oral presentation

  • Activity dependent myelin regulation in information processing

    Wake Hiroaki

    第115回IIISセミナー, Aug. 2017, Japanese, IIISセミナー, 茨城, Domestic conference

    Oral presentation

  • 2光子顕微鏡による生体イメージング

    Wake Hiroaki

    京都大学セミナー, Aug. 2017, Japanese, 京都大学, 京都, Domestic conference

    Public discourse

  • 髄鞘制御不全による情報処理異常の可視化

    Wake Hiroaki

    大阪大学生命機能セミナー, Jul. 2017, Japanese, 大阪大学, 大阪, Domestic conference

    Oral presentation

  • 光で迫る脳免疫細胞の機能

    Wake Hiroaki

    第40回日本神経科学大会, Jul. 2017, Japanese, 日本神経科学大会, 千葉, Domestic conference

    [Invited]

    Nominated symposium

  • Microglia sense systemic immune status to modify activity of neuronal circuit; 免疫状態依存的なミクログリアによる神経回路活動の制御

    Koichiro Haruwaka, Wake Hiroaki, Junichi Nabekura

    第40回日本神経科学大会, Jul. 2017, Japanese, 日本神経科学大会, 千葉, Domestic conference

    Poster presentation

  • Lipid composition of frontal white matter is altered with motor learning.

    Yukio Tsuji, Tachibana Yoshihisa, Fumiyoshi Yamazaki, Daisuke Kato, Shinohara Masakazu, Miyamoto Akiko, Ikuko Yao, Toda Tatsushi, Mitsutoshi Setou, Wake Hiroaki

    第40回日本神経科学大会, Jul. 2017, English, 日本神経科学大会, 千葉, Domestic conference

    Poster presentation

  • 身体疾患で惹起される免疫変容が起こす神経回路恒常性の破綻と精神症状の解明

    Wake Hiroaki

    さきがけ領域会議, Jun. 2017, Japanese, さきがけ領域会議, 秋田, Domestic conference

    Oral presentation

  • 光で迫る脳免疫細胞の機能

    Wake Hiroaki

    脳科学の達人2017, Jun. 2017, Japanese, 脳科学の達人2017市民講座プレ企画@未来館, 東京, Domestic conference

    Public symposium

  • 光で照らし出すグリアの新機能および脳機能表出

    Wake Hiroaki

    Glial assembly, The 5th Summer Workshop, Jun. 2017, Japanese, Glial assembly, 新潟, Domestic conference

    Oral presentation

  • Microglia Sense Systemic Immune Status to Modify Activity of Neuronal Circuit

    Koichiro Haruwaka, Wake Hiroaki, Junichi Nabekura

    Glial assembly, The 4th Summer Workshop, Jun. 2017, English, Glial assembly, 新潟, Domestic conference

    Poster presentation

  • 革新的予防・診断・治療法開発に向けたシグナル伝達医学研究

    Wake Hiroaki

    神戸大学先端融合研究環新規プロジェクトキックオフシンポジウム, May 2017, Japanese, 神戸大学先, 神戸, Domestic conference

    Oral presentation

  • 横浜市立大学「神経医科学序説」における講義

    Wake Hiroaki

    神経医科学序説, May 2017, Japanese, 横浜市立大学, 横浜, Domestic conference

    Public discourse

  • 生体適合性マイクロチップレーザーを用いた高次脳機能の4次元操作

    Wake Hiroaki

    融合発展促進研究プロジェクト中間実績報告会, Apr. 2017, Japanese, 融合発展促進研究プロジェクト, 東京, Domestic conference

    Oral presentation

  • 髄鞘制御不全による情報処理異常の可視化

    Wake Hiroaki

    第29回臨床MR脳機能研究会, Apr. 2017, Japanese, 臨床MR脳機能研究会, 東京, Domestic conference

    [Invited]

    Invited oral presentation

Research Projects

  • 和氣 弘明

    科学研究費補助金/基盤研究(B), Apr. 2018 - Mar. 2021, Principal investigator

    Competitive research funding

  • 和氣 弘明

    学術研究助成基金助成金/挑戦的研究(萌芽), Apr. 2017 - Mar. 2019, Principal investigator

    Competitive research funding

  • 和氣 弘明

    科学研究費補助金/新学術領域研究, Apr. 2017 - Mar. 2019, Principal investigator

    Competitive research funding

  • 和氣 弘明

    科学研究費補助金/新学術領域研究, Apr. 2015 - Mar. 2018, Principal investigator

    Competitive research funding

  • 和氣 弘明

    科学研究費一部基金/若手研究(A), Apr. 2014 - Mar. 2018, Principal investigator

    Competitive research funding

  • 和氣 弘明

    科学研究費補助金/新学術領域研究, Apr. 2015 - Mar. 2017, Principal investigator

    Competitive research funding

  • ホログラム光刺激による神経回路再編の人為的創出

    和氣 弘明

    国立研究開発法人科学技術振興機構, 戦略的創造研究推進事業(CREST), 2017, Principal investigator

    Competitive research funding

  • 身体疾患で惹起される免疫変容が起こす神経回路恒常性の破綻と精神症状の解明

    和氣 弘明

    国立研究開発法人科学技術振興機構, 戦略的創造研究推進事業(さきがけ), 2016, Principal investigator

    Competitive research funding

  • 和氣 弘明

    文部科学省, 科学研究費補助金(新学術領域研究(研究領域提案型)), 2013 - 2014, Principal investigator

    Competitive research funding

  • 和氣 弘明

    文部科学省, 科学研究費補助金(新学術領域研究(研究領域提案型)), 2013 - 2014, Principal investigator

    Competitive research funding

  • 和氣 弘明

    文部科学省, 科学研究費補助金(研究活動スタート支援), 2012 - 2013, Principal investigator

    Competitive research funding

  • 和氣 弘明

    文部科学省, 科学研究費補助金(若手研究(B)), 2008 - 2009, Principal investigator

    本研究課題において申請者はミクログリア細胞の神経可塑性に対する関与を検討した。申請者はまず大脳皮質第5層錐体細胞にEGFPを発現する遺伝子改変マウスとionized calcium-binding adaptor molecule 1(IBA-1)promotorの下流にEGFPを導入した遺伝子改変マウスを交配させ、得られた遺伝子改変マウスは錐体細胞およびマイクログリアに選択的に蛍光標識される個体を用い、2光子励起顕微鏡を適用し同動物脳を生体麻酔科において観察を行った。またミクログリア細胞の障害脳における神経可塑性への関与も検討するため、レーザーを用いた脳虚血モデルマウスの作成を行い、正常動物との比較を行った。(結果)正常脳においてミクログリア細胞は1時間に一度5分間神経シナプス部に接触し、この接触は神経活動に依存し、低体温や感覚除去により神経活動を減弱させるとその接触頻度は低下することを証明した。またシナプス特異的に接触することを、同一樹状突起状のシナプス接触を観察することにより

    Competitive research funding