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MORITA Mitsuhiro
Graduate School of Science / Division of Biology
Associate Professor

Researcher basic information

■ Research Keyword
  • 包括脳ネットワーク
  • アストロサイト
  • カルシウム
  • 脳損傷
■ Research Areas
  • Life sciences / Clinical pharmacy
  • Life sciences / Physiology
■ Committee History
  • Jul. 2020 - Present, Frontiers in Cellular Neuroscience, Review Editor (Non-Neuronal Cells)
  • Neural Regeneration Research, Editorial Board Member

Research activity information

■ Award
  • Mar. 2005 日本薬理学会, Journal of Pharmacological Sciences 優秀論文賞

■ Paper
  • Yoshihito Saito, Yuma Osako, Maya Odagawa, Yasuhiro Oisi, Chie Matsubara, Shigeki Kato, Kazuto Kobayashi, Mitsuhiro Morita, Joshua P Johansen, Masanori Murayama
    Emotional arousal plays a critical role in determining what is remembered from experiences. It is hypothesized that activation of the amygdala by emotional stimuli enhances memory consolidation in its downstream brain regions. However, the physiological basis of the inter-regional interaction and its functions remain unclear. Here, by adding emotional information to a perceptual recognition task that relied on a frontal-sensory cortical circuit in mice, we demonstrated that the amygdala not only associates emotional information with perceptual information but also enhances perceptual memory retention via amygdalo-frontal cortical projections. Furthermore, emotional association increased reactivation of coordinated activity across the amygdalo-cortical circuit during non-rapid eye movement (NREM) sleep but not during rapid eye movement (REM) sleep. Notably, this increased reactivation was associated with amygdala high-frequency oscillations. Silencing of amygdalo-cortical inputs during NREM sleep selectively disrupted perceptual memory enhancement. Our findings indicate that inter-regional reactivation triggered by the amygdala during NREM sleep underlies emotion-induced perceptual memory enhancement.
    Mar. 2025, Neuron, 113(6) (6), 931 - 948, English, International magazine
    [Refereed]
    Scientific journal

  • Rena Fujii, Yuri Nambu, Nitin Sawant Shirikant, Eriko Furube, Mitsuhiro Morita, Ryoichi Yoshimura, Seiji Miyata
    Neural stem cells and/or progenitor cells (NSCs/NPCs) in the subventricular and subgranular zones of the adult mammal forebrain generate new neurons and are involved in partial repair after injury. Recently, NSCs/NPCs were identified in the area postrema (AP) of the medulla oblongata of the hindbrain. In this study, we used the properties of fenestrate capillaries to observe specific neuronal elimination in the AP of adult mice and investigated subsequent neuronal regeneration by neurogenesis. Subcutaneous administration of monosodium glutamate (MSG) induced prominent Fos expression in HuC/D+ neurons in the AP 2 h after administration. MSG administration caused a marked decrease in HuC/D+ neuronal density by neuronal death 3 to 21 days after administration, which recovered to the control level 35 days later. After MSG administration, the density of TUNEL+ dying neurons and phagocytic microglia surrounding or engulfing neurons increased. Within 7 days of MSG administration, the number of BrdU+ Sox2+ and BrdU+ Math1+ cells increased markedly, and at least the BrdU+ Math1+ cells similarly increased for the next following 7 days. A remarkable number of HuC/D+ neurons with BrdU+ nuclei were observed 35 days after MSG administration. This study reveals that neurogenesis occurs in the AP of adult mice, recovering and maintaining normal neuronal density after neuronal death.
    Nov. 2024, Neuroscience, 563, 188 - 201, English, International magazine
    [Refereed]
    Scientific journal

  • Nitin Sawant, Airi Watanabe, Haruna Ueda, Hideyuki Okano, Mitsuhiro Morita
    Elsevier BV, Apr. 2024, Experimental Neurology, 374, 114700 - 114700
    [Refereed]
    Scientific journal

  • Mitsuhiro Morita
    Microscopy started as the histological analysis based on intrinsic optical properties of tissues such as the refractive index and light absorption, and is expanding to include the visualization of organelles by chemical staining, localization of molecules by immunostaining, physiological measurements such as Ca2+ imaging, functional manipulation by optogenetics, and comprehensive analysis of chemical composition by Raman spectra. The microscope is one of the most important tools in neuroscience, which aims to reveal the complex intercellular communications underlying brain function and pathology. Many aspects of astrocytes, including the structures of their fine processes and physiological activities in concert with neurons and blood vessels, were revealed in the course of innovations in modern microscopy. The evolution of modern microscopy is a consequence of breakthroughs in spatiotemporal resolutions and expansions in molecular and physiological targets due to the progress in optics and information technology, as well as the inventions of probes using organic chemistry and molecular biology. This review overviews the modern microscopic approach to astrocytes.
    Mar. 2023, International journal of molecular sciences, 24(6) (6), English, International magazine
    [Refereed]
    Scientific journal

  • Daisuke Kato, Xiangyu Quan, Yuta Tanisumi, Zhongtian Guo, Mitsuhiro Morita, Tetsuya Takiguchi, Osamu Matoba, Hiroaki Wake
    Recent advances in optical bioimaging and optogenetics have enabled the visualization and manipulation of biological phenomena, including cellular activities, in living animals. In the field of neuroscience, detailed neural activity related to brain functions, such as learning and memory, has now been revealed, and it has become feasible to artificially manipulate this activity to express brain functions. However, the conventional evaluation of neural activity by two-photon Ca2+ imaging has the problem of low temporal resolution. In addition, manipulation of neural activity by conventional optogenetics through the optic fiber can only simultaneously regulate the activity of neurons with the same genetic background, making it difficult to control the activity of individual neurons. To solve this issue, we recently developed a microscope with a high spatiotemporal resolution for biological applications by combining optogenetics with digital holographic technology that can modify femtosecond infrared laser beams. Here, we describe protocols for the visualization, evaluation, and manipulation of neural activity, including the preparation of samples and operation of a two-photon holographic microscope (Figure 1). These protocols provide accurate spatiotemporal information on neural activity, which may be useful for elucidating the pathogenesis of neuropsychiatric disorders that lead to abnormalities in neural activity.
    Sep. 2022, Journal of visualized experiments : JoVE, (187) (187), English, International magazine
    [Refereed][Invited]
    Scientific journal

  • Manoj Kumar, Osamu Matoba, Xiangyu Quan, Sudheesh K Rajput, Mitsuhiro Morita, Yasuhiro Awatsuji
    Apr. 2022, Optics and Lasers in Engineering, 151, 106887 - 106887, English
    [Refereed]
    Scientific journal

  • Yuri Nambu, Koji Ohira, Mitsuhiro Morita, Hiroki Yasumoto, Erkin Kurganov, Seiji Miyata
    Astrocyte- and tanycyte-like neural stem cells (NSCs) were recently detected in the area postrema (AP) and central canal (CC) of the adult medulla oblongata, respectively. The present study aimed to examine dynamical behaviors of the astrocyte- and tanycyte-like NSCs of the mouse medulla oblongata to leptin. The neurosphere assay identified astrocytes in the AP and tanycytes in the CC as NSCs based on their self-renewing neurospherogenic potential. Both NSCs in neurosphere cultures were multipotent cells that generate astrocytes, oligodendrocytes, and neurons. Astrocyte-like NSCs actively proliferated and tanycyte-like NSCs were quiescent under physiologically-relevant in vivo conditions. Chronic leptin treatment promoted proliferation of astrocyte-like NSCs in the AP both in vitro and in vivo. Leptin receptors were expressed in astrocyte-like, but not tanycyte-like NSCs. Food deprivation significantly diminished proliferation of astrocyte-like NSCs. Therefore, the present study indicates that proliferation of astrocyte-like, but not tanycyte-like NSCs is regulated by nutritional conditions.
    May 2021, Neuroscience research, 173, 44 - 53, English, International magazine
    [Refereed]
    Scientific journal

  • Manoj Kumar, Osamu Matoba, Mitsuhiro Morita, Yasuhiro Awatsuji
    2021, Proceedings of SPIE - The International Society for Optical Engineering, 11925
    [Refereed]
    International conference proceedings

  • Maja Potokar, Mitsuhiro Morita, Gerhard Wiche, Jernej Jorgačevski
    Despite the remarkable complexity of the individual neuron and of neuronal circuits, it has been clear for quite a while that, in order to understand the functioning of the brain, the contribution of other cell types in the brain have to be accounted for. Among glial cells, astrocytes have multiple roles in orchestrating neuronal functions. Their communication with neurons by exchanging signaling molecules and removing molecules from extracellular space takes place at several levels and is governed by different cellular processes, supported by multiple cellular structures, including the cytoskeleton. Intermediate filaments in astrocytes are emerging as important integrators of cellular processes. Astrocytes express five types of intermediate filaments: glial fibrillary acidic protein (GFAP); vimentin; nestin; synemin; lamins. Variability, interactions with different cellular structures and the particular roles of individual intermediate filaments in astrocytes have been studied extensively in the case of GFAP and vimentin, but far less attention has been given to nestin, synemin and lamins. Similarly, the interplay between different types of cytoskeleton and the interaction between the cytoskeleton and membranous structures, which is mediated by cytolinker proteins, are understudied in astrocytes. The present review summarizes the basic properties of astrocytic intermediate filaments and of other cytoskeletal macromolecules, such as cytolinker proteins, and describes the current knowledge of their roles in normal physiological and pathological conditions.
    Jul. 2020, Cells, 9(7) (7), English, International magazine
    [Refereed]
    Scientific journal

  • Eriko Furube, Haruna Ishii, Yuri Nambu, Erkin Kurganov, Sumiharu Nagaoka, Mitsuhiro Morita, Seiji Miyata
    Tanycyte is a subtype of ependymal cells which extend long radial processes to brain parenchyma. The present study showed that tanycyte-like ependymal cells in the organum vasculosum of the lamina terminalis, subfornical organ and central canal (CC) expressed neural stem cell (NSC) marker nestin, glial fibrillar acidic protein and sex determining region Y. Proliferation of these tanycyte-like ependymal cells was promoted by continuous intracerebroventricular infusion of fibroblast growth factor-2 and epidermal growth factor. Tanycytes-like ependymal cells in the CC are able to form self-renewing neurospheres and give rise mostly to new astrocytes and oligodendrocytes. Collagenase-induced small medullary hemorrhage increased proliferation of tanycyte-like ependymal cells in the CC. These results demonstrate that these tanycyte-like ependymal cells of the adult mouse brain are NSCs and suggest that they serve as a source for providing new neuronal lineage cells upon brain damage in the medulla oblongata.
    Feb. 2020, Scientific reports, 10(1) (1), 2826 - 2826, English, International magazine
    [Refereed]
    Scientific journal

  • Sudheesh K. Rajput, Manoj Kumar, Xiangyu Quan, Mitsuhiro Morita, Tomoyuki Furuyashiki, Yasuhiro Awatsuji, Enrique Tajahuerce, Osamu Matoba
    SPIE-Intl Soc Optical Eng, Nov. 2019, Journal of Biomedical Optics, 25(03) (03), 1 - 1
    [Refereed]
    Scientific journal

  • Daishi Hiratsuka, Erkin Kurganov, Eriko Furube, Mitsuhiro Morita, Seiji Miyata
    The myelin sheath is critical in maintaining normal functions of the adult central nervous system (CNS) and the loss of the myelin sheath results in various neurological diseases. Although remyelination is the intrinsic repair system against demyelination that new myelin sheath is formed around axons in the adult CNS, little has been reported on remyelination system in the medulla oblongata. In the present study, we showed that the proliferation of oligodendrocyte progenitor cells (OPCs) was increased in the medulla oblongata by lysophosphatidylcholine (LPC)-induced focal demyelination, but that of NSCs was not changed. The inhibition of vascular endothelial growth factor (VEGF)- and platelet-derived growth factor (PDGF)-signaling suppressed the proliferation of OPCs by LPC-induced demyelination. Thus, the present study indicates that resident OPCs contribute to focal remyelination and VEGF and PDGF signaling is required for the proliferation of OPCs in the medulla oblongata of the adult mouse.
    Jul. 2019, Journal of neuroimmunology, 332, 176 - 186, English, International magazine
    [Refereed]
    Scientific journal

  • Shohei Takagi, Eriko Furube, Yousuke Nakano, Mitsuhiro Morita, Seiji Miyata
    Microglia are the primary resident immune cells of the brain parenchyma and transform into the amoeboid form in the "activated state" under pathological conditions from the ramified form in the "resting state" under physiologically healthy conditions. In the present study, we found that microglia in the circumventricular organs (CVOs) of adult mice displayed the amoeboid form with fewer branched cellular processes even under normal conditions; however, those in other brain regions showed the ramified form, which is characterized by well-branched and dendritic cellular processes. Moreover, microglia in the CVOs showed the strong protein expression of the M1 markers CD16/32 and CD86 and M2 markers CD206 and Ym1 without any pathological stimulation. Thus, the present results indicate that microglia in the CVOs of adult mice are morphologically and functionally activated under normal conditions, possibly due to the specialized features of the CVOs, namely, the entry of blood-derived molecules into parenchyma through fenestrated capillaries and the presence of neural stem cells.
    Jun. 2019, Journal of neuroimmunology, 331, 74 - 86, English, International magazine
    [Refereed]

  • Morita M, Ikeshima-Kataoka H, Kreft M, Vardjan N, Zorec R, Noda M
    Feb. 2019, International journal of molecular sciences, 20(4) (4)
    [Refereed]

  • Daishi Hiratsuka, Eriko Furube, Katsutoshi Taguchi, Masaki Tanaka, Mitsuhiro Morita, Seiji Miyata
    Experimental autoimmune encephalomyelitis (EAE) is primarily used as an animal model of autoimmune demyelinating disease, multiple sclerosis. In this study, we found the proliferative rate of oligodendrocyte progenitor cells (OPCs) in the medulla elevated twofold above control levels during EAE and new generation of mature oligodendrocytes was increased as well. Although astrocytes showed hypertrophic reactive phenotype, a new generation of them was rare. Astrocyte- and tanycyte-like neural stem cells (NSCs), multipotent NSCs, did not augment their low proliferative rate. Thus, the present study demonstrates that resident OPCs derived from NSCs contribute to remyelination in the medulla oblongata in EAE mice.
    Jun. 2018, Journal of neuroimmunology, 319, 41 - 54, English, International magazine
    [Refereed]
    Scientific journal

  • Satoko Ueno, Hiroshi Miyoshi, Yoko Maruyama, Mitsuhiro Morita, Shohei Maekawa
    Elsevier Ireland Ltd, May 2018, Neuroscience Letters, 675, 59 - 63, English
    [Refereed]
    Scientific journal

  • Ueno, S, Miyoshi, H, Maruyama, Y, Morita, M, Maekawa, S
    May 2018, International Journal of Lipids, 1(1) (1), 1 - 10, English
    [Refereed]
    Scientific journal

  • Yoko Maruyama, Satoko Ueno, Mitsuhiro Morita, Fumio Hayashi, Shohei Maekawa
    Elsevier Ireland Ltd, Apr. 2018, Neuroscience Letters, 673, 132 - 135, English
    [Refereed]
    Scientific journal

  • Concise Synthesis of Hydroxy beta-Methyl Fatty Acid Ethyl Esters
    Yuki Sakai, Yukiko Asakura, Mitsuhiro Morita, Takashi Takahashi
    Dec. 2017, CHEMICAL & PHARMACEUTICAL BULLETIN, 65(12) (12), 1195 - 1198, English
    [Refereed]
    Scientific journal

  • Yuki Fujii, Shohei Maekawa, Mitsuhiro Morita
    Oct. 2017, SCIENTIFIC REPORTS, 7(1) (1), 13115, English
    [Refereed]
    Scientific journal

  • Kunihiko Yamashiro, Mitsuhiro Morita
    Jun. 2017, NEURAL REGENERATION RESEARCH, 12(6) (6), 881 - 885, English
    [Refereed]

  • Kunihiko Yamashiro, Yuki Fujii, Shohei Maekawa, Mitsuhiro Morita
    Jan. 2017, JOURNAL OF NEUROCHEMISTRY, 140(1) (1), 24 - 36, English
    [Refereed]
    Scientific journal

  • Eriko Furube, Mitsuhiro Morita, Seiji Miyata
    Nov. 2015, CELL AND TISSUE RESEARCH, 362(2) (2), 347 - 365, English
    [Refereed]
    Scientific journal

  • Yuumi Kobayashi, Ronan da Silva, Haruko Kumanogoh, Shinji Miyata, Chihiro Sato, Ken Kitajima, Shun Nakamura, Mistuhiro Morita, Fumio Hayashi, Shohei Maekawa
    Sep. 2015, JOURNAL OF NEUROSCIENCE RESEARCH, 93(9) (9), 1462 - 1470, English
    [Refereed]
    Scientific journal

  • Mitsuhiro Morita, Akira Nakane, Shohei Maekawa, Yoshihisa Kudo
    Sep. 2015, JOURNAL OF PHARMACOLOGICAL SCIENCES, 129(1) (1), 38 - 42, English
    [Refereed]
    Scientific journal

  • Mitsuhiro Morita, Akira Nakane, Yuki Fujii, Shohei Maekawa, Yoshihisa Kudo
    Sep. 2015, PLOS ONE, 10(9) (9), e0137610, English
    [Refereed]
    Scientific journal

  • Shohei Maekawa, Yuumi Kobayashi, Mitsuhiro Morita, Toshinobu Suzaki
    Jul. 2015, NEUROSCIENCE LETTERS, 600, 244 - 248, English
    [Refereed]
    Scientific journal

  • Shohei Maekawa, Yuumi Kobayashi, Sin-Ichi Odagaki, Midori Makino, Haruko Kumanogoh, Shun Nakamura, Mitsuhiro Morita, Fumio Hayashi
    Mar. 2013, NEUROSCIENCE LETTERS, 537, 50 - 54, English
    [Refereed]
    Scientific journal

  • Maowulan Maimaitiyiming, Haruko Kumanogoh, Shun Nakamura, Mitsuhiro Morita, Shohei Maekawa
    Academic Press Inc., Feb. 2013, Protein Expression and Purification, 87(2) (2), 67 - 71, English
    [Refereed]
    Scientific journal

  • Maowulan Maimaitiyiming, Yuumi Kobayashi, Haruko Kumanogoh, Shun Nakamura, Mitsuhiro Morita, Shohei Maekawa
    Feb. 2013, NEUROSCIENCE LETTERS, 534, 322 - 326, English
    [Refereed]
    Scientific journal

  • Takayuki Suzuki, Honami Sakata, Chiaki Kato, John A. Connor, Mitsuhiro Morita
    Dec. 2012, EUROPEAN JOURNAL OF NEUROSCIENCE, 36(12) (12), 3653 - 3664, English
    [Refereed]
    Scientific journal

  • Rika Takaichi, Sin-Ichi Odagaki, Haruko Kumanogoh, Shun Nakamura, Mitsuhiro Morita, Shohei Maekawa
    Jan. 2012, JOURNAL OF NEUROSCIENCE RESEARCH, 90(1) (1), 21 - 27, English
    [Refereed]
    Scientific journal

  • Mitsuhiro Morita, Yoshihisa Kudo
    Dec. 2010, GLIA, 58(16) (16), 1988 - 1995, English
    [Refereed]
    Scientific journal

  • Masahiko Morita, Nobukazu Shitan, Keisuke Sawada, Marc C. E. Van Montagu, Dirk Inze, Heiko Rischer, Alain Goossens, Kirsi-Marja Oksman-Caldentey, Yoshinori Moriyama, Kazufumi Yazaki
    Feb. 2009, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 106(7) (7), 2447 - 2452, English
    [Refereed]
    Scientific journal

  • Mitsuhiro Morita, Kotaro Yoshizaki, Akira Nakane, Yoshihisa Kudo
    Nov. 2007, JOURNAL OF PHARMACOLOGICAL SCIENCES, 105(3) (3), 258 - 263, English
    [Refereed]
    Scientific journal

  • Mitsuhiro Morita, Fumito Yoshiki, Akira Nakane, Yoshiumi Okubo, Yoshihisa Kudo
    Oct. 2007, FEBS JOURNAL, 274(19) (19), 5147 - 5157, English
    [Refereed]
    Scientific journal

  • K. B. Blagoev, B. Mihaila, B. J. Travis, L. B. Alexandrov, A. R. Bishop, D. Ranken, S. Posse, C. Gasparovic, A. Mayer, C. J. Aine, I. Ulbert, M. Morita, W. Muller, J. Connor, E. Halgren
    Aug. 2007, NEUROIMAGE, 37(1) (1), 137 - 148, English
    [Refereed]
    Scientific journal

  • Mitsuhiro Morita, Chihiro Saruta, Nagisa Kozuka, Yoshiumi Okubo, Makoto Itakura, Masami Takahashi, Yoshihisa Kudo
    Apr. 2007, GLIA, 55(5) (5), 508 - 515, English
    [Refereed]
    Scientific journal

  • N. Kozuka, Y. Kudo, M. Morita
    Feb. 2007, NEUROSCIENCE, 144(3) (3), 911 - 919, English
    [Refereed]
    Scientific journal

  • Yoshitoku Yoshida, Haruno Kumagai, Yoshiumi Ohkubo, Remi Tsuchiya, Mitsuhiro Morita, Hiroyoshi Miyakawa, Yoshihisa Kudo
    Sep. 2006, JOURNAL OF PHARMACOLOGICAL SCIENCES, 102(1) (1), 121 - 128, English
    [Refereed]
    Scientific journal

  • M Hirabayashi, M Kato, R Kaneko, T Hirabayashi, M Morita, S Hochi
    Apr. 2006, EXPERIMENTAL ANIMALS, 55(2) (2), 131 - 135, English
    [Refereed]
    Scientific journal

  • Y Yoshida, A Nakane, M Morita, Y Kudo
    Feb. 2006, JOURNAL OF PHARMACOLOGICAL SCIENCES, 100(2) (2), 126 - 132, English
    [Refereed]
    Scientific journal

  • M Morita, J Susuki, H Amino, F Yoshiki, S Moizumi, Y Kudo
    2006, NEUROSCIENCE, 137(2) (2), 545 - 553, English
    [Refereed]
    Scientific journal

  • N Kozuka, R Itofusa, Y Kudo, M Morita
    Dec. 2005, JOURNAL OF NEUROSCIENCE RESEARCH, 82(5) (5), 717 - 728, English
    [Refereed]
    Scientific journal

  • M Morita, N Kozuka, R Itofusa, M Yukawa, Y Kudo
    Nov. 2005, JOURNAL OF NEUROCHEMISTRY, 95(3) (3), 871 - 879, English
    [Refereed]
    Scientific journal

  • M Nakahara, M Shimozawa, Y Nakamura, Y Irino, M Morita, Y Kudo, K Fukami
    Aug. 2005, JOURNAL OF BIOLOGICAL CHEMISTRY, 280(32) (32), 29128 - 29134, English
    [Refereed]
    Scientific journal

  • Y Yoshida, R Tsuchiya, N Matsumoto, M Morita, H Miyakawa, Y Kudo
    Feb. 2005, JOURNAL OF PHARMACOLOGICAL SCIENCES, 97(2) (2), 212 - 218, English
    [Refereed]
    Scientific journal

  • [Current calcium imaging systems].
    Kudo Y, Morita M
    Aug. 2004, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme, 49(11 Suppl) (11 Suppl), 1634 - 1640
    [Refereed]

  • A Muroyama, S Uehara, S Yatsushiro, N Echigo, R Morimoto, M Morita, M Hayashi, A Yamamoto, DS Koh, Y Moriyama
    Jul. 2004, DIABETES, 53(7) (7), 1743 - 1753, English
    [Refereed]
    Scientific journal

  • A novel variant of ionotropic glutamate receptor regulates somatostatin secretion from delta cells of islets of Langerhans
    Akiko Muroyama, Shunsuke Uehara, Shouki Yatsushiro, Riyo Morimoto, Noriko Echigo, Mitsuhiro Morita, Mitsuko Hayashi, Akitsugu Yamamoto, Duk-Su Koh, Yoshinori Moriyama
    May 2004, CELL STRUCTURE AND FUNCTION, 29, 107 - 107, English

  • M Morita, J Susuki, T Moto, C Higuchi, Y Kudo
    Jan. 2004, JOURNAL OF PHARMACOLOGICAL SCIENCES, 94(1) (1), 25 - 30, English
    [Refereed]
    Scientific journal

  • Roles of astrocytes-neuron cross talking on synaptic plasticity
    Y Kudo, M Morita, H Miyakawa
    Dec. 2003, JOURNAL OF NEUROCHEMISTRY, 87, 15 - 15, English

  • Dual regulation of calcium oscillation in astrocytes by growth factors and pro-inflammatory cytokines via the mitogen-activated protein kinase cascade
    M Morita, C Higuchi, T Moto, N Kozuka, J Susuki, R Itofusa, J Yamashita, Y Kudo
    Nov. 2003, JOURNAL OF NEUROSCIENCE, 23(34) (34), 10944 - 10952, English
    [Refereed]
    Scientific journal

  • M Morita, F Yoshiki, Y Kudo
    Sep. 2003, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 308(4) (4), 673 - 678, English
    [Refereed]
    Scientific journal

  • Y Yoshida, N Matsumoto, R Tsuchiya, M Morita, H Miyakawa, Y Kudo
    Jul. 2003, JOURNAL OF PHARMACOLOGICAL SCIENCES, 92(3) (3), 245 - 251, English
    [Refereed]
    Scientific journal

  • R Tsuchiya, F Yoshiki, Y Kudo, M Morita
    Nov. 2002, BRAIN RESEARCH, 956(2) (2), 221 - 229, English
    [Refereed]
    Scientific journal

  • Glutamate receptor subunit delta 2 is highly expressed in a novel population of glial-like cells in rat pineal glands in culture
    S Yatsushiro, M Hayashi, M Morita, A Yamamoto, Y Moriyama
    Sep. 2000, JOURNAL OF NEUROCHEMISTRY, 75(3) (3), 1115 - 1122, English
    [Refereed]
    Scientific journal

  • Adverse effects of an active fragment of parathyroid hormone on rat hippocampal organotypic cultures
    T Hirasawa, T Nakamura, A Mizushima, M Morita, Ezawa, I, H Miyakawa, Y Kudo
    Jan. 2000, BRITISH JOURNAL OF PHARMACOLOGY, 129(1) (1), 21 - 28, English
    [Refereed]
    Scientific journal

  • Activation of dihydropyridine sensitive Ca2+ channels in rat hippocampal neurons in culture by parathyroid hormone
    T Hirasawa, T Nakamura, M Morita, Ezawa, I, H Miyakawa, Y Kudo
    Nov. 1998, NEUROSCIENCE LETTERS, 256(3) (3), 139 - 142, English
    [Refereed]
    Scientific journal

  • Microvesicle-mediated exocytosis of glutamate is a novel paracrine-like chemical transduction mechanism and inhibits melatonin secretion in rat pinealocytes
    H Yamada, A Yamamoto, S Yodozawa, S Kozaki, M Takahashi, M Morita, H Michibata, T Furuichi, K Mikoshiba, Y Moriyama
    Oct. 1996, JOURNAL OF PINEAL RESEARCH, 21(3) (3), 175 - 191, English
    [Refereed]
    Scientific journal

  • Mutational analysis of the ligand binding site of the inositol 1,4,5-trisphosphate receptor
    F Yoshikawa, M Morita, T Monkawa, T Michikawa, T Furuichi, K Mikoshiba
    Jul. 1996, JOURNAL OF BIOLOGICAL CHEMISTRY, 271(30) (30), 18277 - 18284, English
    [Refereed]
    Scientific journal

  • THE INOSITOL HIGH-POLYPHOSPHATE SERIES BLOCKS SYNAPTIC TRANSMISSION BY PREVENTING VESICULAR FUSION - A SQUID GIANT SYNAPSE STUDY
    R LLINAS, M SUGIMORI, EJ LANG, M MORITA, M FUKUDA, M NIINOBE, K MIKOSHIBA
    Dec. 1994, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 91(26) (26), 12990 - 12993, English
    [Refereed]
    Scientific journal

  • TRANSMISSION AT THE SQUID GIANT SYNAPSE WAS BLOCKED BY TETANUS TOXIN BY AFFECTING SYNAPTOBREVIN, A VESICLE-BOUND PROTEIN
    R LLINAS, M SUGIMORI, D CHU, M MORITA, J BLASI, J HERREROS, R JAHN, J MARSAL
    May 1994, JOURNAL OF PHYSIOLOGY-LONDON, 477(1) (1), 129 - 133, English
    [Refereed]
    Scientific journal

■ MISC
  • 成体マウス最後野におけるグルタミン酸誘発性神経細胞脱落後の再生
    藤居怜那, 南部有理, SAWANT Nitin Shrikant, 古部瑛莉子, 森田光洋, 吉村亮一, 宮田清司
    2024, 日本生物学的精神医学会(Web), 46th

  • 成体マウス最後野における高濃度グルタミン酸誘発性神経細胞脱落後の修復
    藤居怜那, 南部有理, SHIRIKANT Nitin Sawant, 古部瑛莉子, 古部瑛莉子, 森田光洋, 吉村亮一, 宮田清司
    2024, 日本解剖学会総会・全国学術集会抄録集(CD-ROM), 129th

  • Structure-function elationship of the ligand binding site of the Inositol 1,4,5-Trisphosphate Receptor.
    吉川文生, 森田光洋, 古市貞一, 御子柴克彦
    1995, 日本分子生物学会年会プログラム・講演要旨集, 18th

■ Books And Other Publications
  • 光を用いた生命現象の操作
    森田光洋
    光学 第54巻1号35-37頁, Jan. 2025

  • 命活動の蛍光イメージングの歴史
    森田光洋
    Single work, 光学 第53巻10号432-437頁, Oct. 2024

  • 3次元光計測イメージングとその生命科学及び散乱透視イメージングへの応用
    的場修, 森田光洋
    Joint work, 光技術コンタクト第61巻11号, Nov. 2023

  • 2 光子励起ホログラフィック顕微鏡による高度光遺伝学応用
    的場 修, 全 香玉, 米田 成, 森田 光洋
    Joint work, レーザー研究第 50 巻第 11 号(2022 年 11 月)「多彩な発展を遂げるホログラフィ」特集号, Nov. 2022

  • 実験医学増刊 39(15)「神経免疫 メカニズムと疾患」
    森田光洋, 安井正人
    Joint work, Glymphatic system研究の現状から見たアクアポリンとアルツハイマー病の関連 p2399-2402, 羊土社, Sep. 2021

■ Lectures, oral presentations, etc.
  • Crosstalk between AQP4-dependent ATP/adenosine release and dopamine neurotransmission in cocaine-induced depressive behavior.
    Morita, M.
    Society for Neurosicence, Oct. 2024, English
    Poster presentation

  • コカインの精神症状における AQP4依存的な細胞外アデノシン上 昇とドーパミン神経伝達のクロストーク
    山根里奈, 岡田聡史, 小林昌人, 森田光洋
    第47回日本神経科学学会, Jul. 2024, English
    Poster presentation

  • 扁桃体-皮質回路は情動による記憶強化を担う
    齋藤 喜仁, 大迫 優真, 小田川 摩耶, 大石 康博, 松原 智恵, 加藤 成樹, 小林 和人, 森田 光洋, Joshua Johansen, 村山 正宜
    第47回日本神経科学学会, Jul. 2024, English
    Poster presentation

  • Optimization of All-Optical Physiology by Two-Photon Holographic Microscope for Avoiding Crosstalk between Opsin and Ca2+ indicator.
    Priyanka Suresh Gore, Manoj Kumar, Naru Yoneda, Osamu Matoba, Mitsuhiro Morita
    Neuro2024, Jul. 2024, English
    Poster presentation

  • Crosstalk between AQP4-dependent increase of extracellular adenosine and dopamine neurotransmission during cocaine-induced psychiatric behaviors.
    Rina Yamane, Satoshi Okada, Masato Kobayashi, Mitsuhiro Morita
    FENS Forum 2024, Jun. 2024, English
    Poster presentation

  • Optimization of All-Optical Physiology by Two-Photon Holographic Microscope for Avoiding Crosstalk Problem
    Priyanka Gorea, Manoj Kumarb, Naru Yonedab, Osamu Matobab, Mitsuhiro Morita
    OPTICS & PHOTONICS International Congress 2024/BISC2024., Apr. 2024, English
    Oral presentation

  • 生命活動の観察・操作を可能にするホログラフィック顕微鏡と散乱透視イメージング
    的場修, 森田光洋
    第99回レーザー加工学会, Nov. 2023, Japanese
    [Invited]
    Invited oral presentation

  • Impaired recovery from focal closed-head injury by STAT3 ablation in perilesional reactive astrocyte
    Sawant Nitin, Morita Mitsuhiro
    第46回日本神経科学会, Aug. 2023, English
    Poster presentation

  • Holographic microscope free from nonspecific opsin activation by imaging laser, “crosstalk”
    Priyanka Gore, Yuya Atomura, Manoj Kumar, Xiangyu Quan, Osamu Matoba, Hiroaki Wake, Mitsuhiro Morita
    第46回日本神経科学会, Aug. 2023, English
    Poster presentation

  • Analysis of Local Intracellular Signaling in Astrocytes Using Two-Photon Holographic Microscopy
    M. Morita, Y. Atomura, P. Gora, M. Kumar, X. Quan, O. Matoba, H. Wake
    European Meeting on Glial Cells in Health and Disease, 2023, English
    Poster presentation

  • 脳における水システムと神経情報処理のクロストーク
    森田光洋
    日本薬理学会・シンポジウム「Glymphatic System の生理と病理;脳内薬物動態の新展開」, Dec. 2022
    [Invited]
    Public symposium

  • Emotional arousal enhances perceptual memory through amygdalo-cortical input during NREM sleep
    Yoshihito Saito, Yuma Osako, Maya Odagawa, Yasuhiro Oisi, Chie Matsubara, Mitsuhiro Morita, Masanori Murayama
    NEURO2022, Aug. 2022
    Poster presentation

  • Cortical-wide impairment of “the Glymphatic System” after focal brain injury
    Lee, H, Azuma, M, Shinzaki, K, Yamane, R, Morita, M
    NEURO2022, Aug. 2022
    Poster presentation

  • Effects of fingolimod on vasculature and glial scar formation after closed-head injury
    Sawant, N, Okazaki, N, Morita, M
    NEURO2022, Aug. 2022
    Poster presentation

  • Crosstalk between AQP4-dependent ATP/Adenosine release and dopamine system in cocaine-induced depressive behavior
    Morita, M, Okada, S, Kobayashi, M
    第44回日本神経科学会, Japanese
    Oral presentation

  • ATP/Adenosine release and dopamine system in cocaine-induced depressive behavior
    Morita, M, Okada, S, Kobayashi, M
    第43回日本神経科学会, 2020
    Poster presentation

  • Upregulated glutamate response and oscillation of [Ca2+]i increases of perilesional reactive astrocyte after closed-head injury
    Ueda, H, Morita, M
    第43回日本神経科学会

  • Mesenchymal stem cell promotes sphere-formation and de-differentiation of astrocytes
    Sunhwa, G, Saito, Y, Morita, M
    第43回日本神経科学会
    Poster presentation

  • 脳損傷周辺に集積するネスチン陽性活性化アストロサイトは複数の由来を持つ
    森田光洋, 岡崎夏樹, 松田ひなた, 辻恵里香
    第60回日本脳循環代謝学会, Nov. 2017, Japanese, 千里ライフサイエンス(大阪), Domestic conference
    Oral presentation

  • 脳髄間葉系幹細胞によるアストロサイトの多分可能促進
    齋藤喜仁, 森田光洋
    第60回日本脳循環代謝学会, Nov. 2017, Japanese, 千里ライフサイエンス(大阪), Domestic conference
    Oral presentation

  • Multiple origins of perilesional nestin-expressing reactive astrocytes following closed-head injury
    Morita, M, Okazaki, N, Tsuji, E
    第60回日本神経化学会, Oct. 2017, English, 仙台国際センター(宮城), Domestic conference
    Oral presentation

  • MULTIPLE ORIGINS OF PERILESIONAL NESTIN-EXPRESSING REACTIVE ASTROCYTES FOLLOWING CLOSED-HEAD INJURY
    Morita, M, Okazaki, N, Tsuji, E
    ISN-ESN Meeting, Jul. 2017, English, Le Palais des Congres de Paris(フランス), International conference
    Poster presentation

  • Multiple origins of perilesional nestin-expressing reactive astrocytes following closed-head injury
    Morita, M, Okazaki, N, Tsuji, E
    第40回日本神経科会, Jul. 2017, English, 幕張メッセ(千葉), Domestic conference
    Oral presentation

  • Localization of neural stem cells and stroke-induced generation of new neurons and glia in the medulla oblongata
    Furube, E, Hiratsuka, D, Taguchi, K, Tanaka, M, Morita, M, Miyata, S
    第40回日本神経科会, Jul. 2017, English, 幕張メッセ(千葉), Domestic conference
    Poster presentation

  • Generation of new oligodendrocytes in the medulla oblongata of mice by EAE-induced demyelination
    Hiratsuka, D, Furube, E, Morita, M, Miyata, S
    第40回日本神経科会, Jul. 2017, English, 幕張メッセ(千葉), Domestic conference
    Poster presentation

  • Bone marrow derived mesenchymal stem cells promote the multipotency of nestin-expressing reactiove astrocytes
    Saito, Y, Morita, M
    第40回日本神経科会, Jul. 2017, English, 幕張メッセ(千葉), Domestic conference
    Poster presentation

  • 骨髄間葉系幹細胞によるアストロサイトの神経幹細胞への脱分化促進
    Morita, Mitsuhiro
    神経組織培養研究会, Nov. 2016, Japanese, 横浜, Domestic conference
    Poster presentation

  • Two distinct propagation mechanisms underlying mechanically-induced calcium waves in astrocytes
    Morita, Mitsuhiro, Fujii Yuki
    FENS, Jul. 2016, English, Copenhagen, Denmark, International conference
    Poster presentation

  • Proximal propagation of mechanically-induced calcium wave between astrocytes is mediated by gap junction, while distal propagation is mediated by diffusion of ATP released by volume-regulated anion channel
    Morita, Mitsuhiro, Fujii Yuki
    日本神経科学会, Jul. 2016, Japanese, 横浜, Domestic conference
    Poster presentation

  • 感知系脳室周囲器官のタニサイト様神経幹細胞
    古部 瑛莉子, 森田 光洋, 宮田 清司
    日本内分泌学会雑誌, Sep. 2015, Japanese, (一社)日本内分泌学会

  • Perilesional nestin-expressing reactive astrocyte is required for cortical recovery after focal brain injury and ablated after wound healing.
    Morita, M, Watanabe, A, Tsuji, E, Maekawa, S
    Euroglia; XII European Meeting on Glial Cells in Health and Disease, 2015, English, International conference
    Poster presentation

  • Neural stem cells and progenitor cells in the sensory circumventricular organs of adult mouse
    Furube, E, Morita, M, Miyata, S
    The 38th Annual Meeting of the Japan Neuroscience Society, 2015, Japanese, Domestic conference
    Poster presentation

  • Broad impairment of the flow of cerebrospinal fluid, glymphatic system after focal closed head injury
    Sakakibara, R, Morita, M
    The 38th Annual Meeting of the Japan Neuroscience Society, 2015, Japanese, Domestic conference
    Poster presentation

  • Ablation of nestin-expressing reactive astrocytes after cortical tissue regeneration in a closed-head injury model
    Morita, M, Tsuji, E, Watanabe, A
    The 38th Annual Meeting of the Japan Neuroscience Society, 2015, Japanese, Domestic conference
    Poster presentation

  • Two adenosine release mechanisms in rat hippocampus
    Fujii,Y, Yamashiro,K, MORITA MITSUHIRO
    Neuroscience 2014(日本神経科学会), 2014, English, 横浜, Domestic conference
    Poster presentation

  • STAT3 signaling in perilesional nestin-expressing reactive astrocyte is required for cortical recovery after closed-head injury.
    Watanabe,A, MORITA MITSUHIRO
    Neuroscience 2014(日本神経科学会), 2014, English, 横浜, Domestic conference
    Poster presentation

  • STAT3 Signaling in Perilesional Nestin-Expressing Reactive Astrocyte is Required for Cortical Recovery after Closed-Head Injury
    MORITA MITSUHIRO, Watanabe,A
    Society for Neurosci,, 2014, English, Washington DC, International conference
    Poster presentation

  • Regulatory effect of NAP-22 on the activity of calcineurin.
    小林 優美, 熊ノ郷 晴子, MORITA MITSUHIRO, 中村 俊, MAEKAWA SHOHEI
    Neuro 2013 (第36回日本神経科学大会), Jun. 2013, English, 国立京都国際会館, Domestic conference
    Oral presentation

  • Interaction of NAP-22 with brain glutamic acid decarboxylase(GAD)
    MAEKAWA SHOHEI, 小林 優美, 小田垣 真一, 牧野 碧, 熊ノ郷 晴子, 中村 俊, MORITA MITSUHIRO, 林 文夫
    Neuro 2013 (第36回日本神経科学大会), Jun. 2013, English, 国立京都国際会館, Domestic conference
    Oral presentation

  • 新規脳傷害モデル「光傷害」における脳組織再生とグリア細胞の活性化
    MORITA MITSUHIRO
    第25回日本脳循環代謝学会総会, 2013, Japanese, 札幌, Domestic conference
    Oral presentation

  • he evoked increase of extracellular adenosine in rat hippocampus CA1 region depends on L-type Ca2+ channel.
    Morita Mitsuhiro, Yamashiro, K
    Neuro2013, 2013, English, Kyoto, Domestic conference
    Oral presentation

  • Monitoring adenosine level in rat hippocampal slice by adenosine sensor cell
    Morita Mitsuhiro, Yamashiro, K
    日本神経科学科会, 2012, English, 名古屋, International conference
    Oral presentation

  • Monitoring adenosine level in rat hippocampal slice by adenosine sensor cell
    Morita Mitsuhiro, Yamashiro, K
    Society for Neuroscience, 2012, English, New Orleans, International conference
    Oral presentation

  • Adenosine release in rat hippocampal slice measured by a novel adenosine sensor cell
    Morita Mitsuhiro, Yamashiro, K
    The 11th Biennial Meeting of the Asian Pacific Society for Neurochemistry / The 55th Annual Meeting for the Japanese Society for Neurochemistry, 2012, English, 神戸, International conference
    Oral presentation

  • Perilesional nestin-expressing reactive astrocytes and cortical tissue recovery in a novel closed-head injury model, photo injury
    MORITA Mitsuhiro
    10th European Meeting on Glial Cells in Health and Disease, Sep. 2011, English, Prague, Czech Republic, International conference
    Poster presentation

  • Perilesional nestin-expressing reactive astrocytes and cortical tissue recovery in a novel closed-head injury model, photo injury
    MORITA Mitsuhiro
    Gordon Research Conference, Mar. 2011, English, Los Angels,USA, International conference
    Poster presentation

  • Perilesional nestin-expressing reactive astrocytes and the cortical tissue recovery of a novel brain injury model (photo injury)
    MORITA Mitsuhiro
    内藤カンファレンスGlial Biology, Oct. 2010, English, 内藤財団, 逗子, Domestic conference
    Poster presentation

  • Perilesional nestin-expressing reactive astrocytes in a novel brain injury model (photo injury)
    MORITA Mitsuhiro
    Neuro2010, Sep. 2010, English, 日本神経科学会, 神戸, Domestic conference
    Poster presentation

■ Affiliated Academic Society
  • 日本神経科学会
    Jul. 1993

■ Research Themes
  • AQP4-dependent ATP/Adenosine releaser from astrocyte following neuronal activities
    森田 光洋, 塚本 寿夫
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2022 - 31 Mar. 2025

  • Construction of further biased optical control tools manipulating GPCR signalings
    塚本 寿夫, 森田 光洋
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2021 - 31 Mar. 2025

  • AQP4に対する高感度かつ選択的な高品質のPET薬剤の実用化
    豊原 潤, 森田 光洋
    日本学術振興会, 科学研究費助成事業, 基盤研究(C), 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 01 Apr. 2021 - 31 Mar. 2024
    本研究では、最新の標識化学の知見を活用して、「AQP4に対する高感度かつ選択的な高品質のPET薬剤の実用化」を目的とする。APQに対するPET薬剤として、[11C]TGN-020が提案されているが、比放射能が低く極めて収率が悪い(1%以下)のため、標識合成法の改良を実施した。Bongarzoneらによる、Cu(I)触媒を用いたボロン酸エステルの[11C]カルボキシル化反応を用いて、中間体の[11C]ニコチン酸を合成した。モレキュラーシーブにより[11C]CO2を濃縮した場合、反応容器への[11C]CO2のトラップ率50%、ニコチン酸への反応効率60%で[11C]ニコチン酸が得られた。次のアミド結合生成反応には、第一段階で使用する触媒の影響で反応が進行しなかったため、固相抽出による[11C]ニコチン酸の簡易精製の方法を検討している。 TGN-020は脳脈絡叢に発現するAQP1に対しても親和性があるため、選択性が悪い。一方、これに対して近年報告されたARE-270はTGN-020に比べ、AQP4に対して高い親和性と選択性を有する。そこで、ARE-270のトリフルオロメチル基に着目して、[18F]ARE-270の標識合成を検討した。[18F]ARE-270の標識合成は、Hubianらによる[18F]トリフルオロメチル銅錯体と芳香族ヨウ素化合物のクロスカップリングを用いて[18F]ARE-270の標識合成を計画した。これまでに、サリチル酸とアニリンの酸塩化物を用いた縮合反応で、標準品のARE-270を70%、標識前駆体のヨウ素体を35%の収率で得た。また、[18F]トリフルオロメチル銅錯体と芳香族ヨウ素化合物のクロスカップリング反応についてモデル化合物による検討を実施し、標識可能であることを確認してた。一方、モデル化合物での検討から、Hubianらによる方法では、加熱条件が過酷であるため、基質によっては分解が促進されることも明らかとなった

  • 森田 光洋
    学術研究助成基金助成金/基盤研究(C), Apr. 2018 - Mar. 2021, Principal investigator
    Competitive research funding

  • 森田 光洋
    学術研究助成基金助成金/基盤研究(C), Apr. 2017 - Mar. 2021, Principal investigator
    Competitive research funding

  • 森田 光洋
    学術研究助成基金助成金/基盤研究(C), Apr. 2014 - Mar. 2017, Principal investigator
    Competitive research funding

  • A-STEP「脳傷害に伴う脳内循環Glymphatic systemの不全を画像化する技術の開発」
    森田 光洋
    科学技術振興機構, 研究成果最適展開支援プログラム フィージビリティスタディステージ 探索タイプ, 2015, Principal investigator
    Competitive research funding

  • A-STEP「脂肪酸放射標識化合物を用いた脳組織再生の画像診断技術の確立」
    森田 光洋
    科学技術振興機構, 研究成果最適展開支援プログラム シーズ顕在化タイプ, 2015, Principal investigator
    Competitive research funding

  • A-STEP「脳傷害に伴う脳内循環Glymphatic systemの不全を画像化する技術の開発」
    森田 光洋
    研究成果最適展開支援プログラム フィージビリティスタディステージ 探索タイプ, 2014, Principal investigator
    Competitive research funding

  • A-STEP「脂肪酸放射標識化合物を用いた脳組織再生の画像診断技術の確立」
    森田 光洋
    研究成果最適展開支援プログラム シーズ顕在化タイプ, 2014, Principal investigator
    Competitive research funding

  • A-STEP「神経保護・再生機能を持つ活性化アストロサイトを検出するための放射性イメージング剤の開発」
    森田 光洋
    研究成果最適展開支援プログラム フィージビリティスタディステージ 探索タイプ, 2013, Principal investigator
    Competitive research funding

  • A-STEP「神経保護・再生機能を持つ活性化アストロサイトを検出するための放射性イメージング剤の開発」
    森田 光洋
    研究成果最適展開支援プログラム フィージビリティスタディステージ 探索タイプ, 2012, Principal investigator
    Competitive research funding

  • 森田 光洋
    科学研究費補助金/新学術領域研究, 2011, Principal investigator
    Competitive research funding

  • 森田 光洋
    科学研究費補助金/基盤研究(B), 2011, Principal investigator
    Competitive research funding

  • 文部科学省, 科学研究費補助金(特定領域研究), 2003 - 2007
    1)高頻度反復シナプス入力によって海馬アストロサイトに誘起されるコンダクタンス上昇の原因を検討した結果、錐体細胞に誘起される新規なプラトー状電位の存在を見出した。この電位はシナプス外NMDA受容体の活性化に起因しており、アストロサイトーニューロン間の相互作用を担うものであることが期待される(論文投稿中)。さらに、この電位の発生に伴い、錐体細胞にNMDA受容体チャネルからの流入に起因するCa上昇が誘起されることを見出した。多くの神経疾患の最終過程としてNMDA受容体の過活性化による細胞障害が仮説として検討されている。アストロサイトからのグルタミン酸放出と神経障害を結ぶ過程として興味深い。 2)成熟動物から作成した海馬スライス内のアストロサイトおよびニューロンが同期的自発Ca変動を示すことをbolus loading法によるCaイメージング法を用いて確認した。また、電気生理的手法により、ニューロンが自発的にプラトー状の電位を発生していることを
    Competitive research funding

  • 文部科学省, 科学研究費補助金(若手研究(B)), 2002 - 2003
    オクトパミンは無脊椎動物にみられる神経伝達物質であり、脊椎動物では合成されず受容体も存在しない。ショウジョウバエのオクトパミン受容体はGタンパク質共役型であり、細胞内カルシウム上昇とcAMP産生を引き起こすことが知られている。オクトパミン受容体遺伝子を脊椎動物由来の細胞に導入した場合、遺伝子発現した細胞選択的に細胞応答が引き起こされると予想される。この点に注目し、複雑な神経回路網において特定の細胞が示すカルシウム上昇などがシステム全体に果たす役割を解明する手段の開発を試みた。具体的にはオクトパミン受容体が脊椎動物細胞において引き起こす細胞応答の解析と、細胞種特異的プロモーターを用いた標的細胞におけるオクトパミン受容体の発現と、これにより引き起こされる神経活動の解析を行った。哺乳動物由来であるPC12h細胞、初代培養神経細胞およびアストロサイトにオクトパミン受容体を発現させた場合、PC12h細胞とアストロサイト
    Competitive research funding

  • 文部科学省, 科学研究費補助金(基盤研究(B)), 1999 - 2002
    本研究の目的は海馬の神経ネットワーク振動の成因を解明することであった。この研究を始めるにいたった動機は、能動性樹状突起と抑制性ニューロンの回路網との相互作用が脳・神経系における情報処理に重要であるという仮説であった。この目的のために、電位感受性色素を用いた光学的手段によって海馬スライス標本の神経活動を観測し、電気生理学的手段によって観測した神経活動とあわせて解析した。最終目的である海馬の神経ネットワーク振動の成因の解明にはいたらなかったが、能動性樹状突起と抑制性ニューロンの回路網との相互作用に関しては着実な成果を挙げることができた。その第一は、海馬CA1錐体細胞樹状突起の全長にわたってシナプス応答が非線型的加算を行い、非線型性はGABA作動性入力によってもたらされていることを明らかにしたものである。.この研究には電気生理学的手法(Hippocampus,2001)と電位感受性蛍光色素を用いた高速光学測定(Neuroscience2002)とを用い
    Competitive research funding

  • 文部科学省, 科学研究費補助金(特定領域研究(B)), 1998 - 2002
    初代培養されたラットのアストロサイトに神経伝達物質を適用した場合のカルシウム応答には大きなばらつきがある。その原因を明らかにする目的で、培養アストロサイトのカルシウム応答に影響を与える因子を検討した。さらに、脳スライス標本を用いて、アストロサイトのカルシウム応答の脳機能における意義を検討した。EGFやBasic FGFのような成長因子はグルタミン酸やATPなどの刺激薬を適用した時や、細胞内IP3受容体を直接活性化させる薬物であるチメロサールを適用した場合のカルシウムオシレーションの発現に必須であることが判明した。これらの成長因子による処置は細胞内カルシウム貯蔵量を増大させ、アストロサイトの形状を繊維状に変化させた。これらの反応は全て炎症性サイトカイン(Interleukin-1β:IL1-βやTumor necrosis factor-α:TNF-α)、Lipopolysaccharide、やMAPK(Mitogen activated cytokinase)の阻害薬、U0126によって抑制された。この事実はカルシウムオシレーション発現にはMAPKが関与し
    Competitive research funding

  • 文部科学省, 科学研究費補助金(奨励研究(A)), 1998 - 1999
    本研究は神経系における特定の細胞集団を蛍光標識し、それらの細胞集団が示す生理反応をそれ以外の細胞から差別化して測定する手法の開発を目的とした。具体的にはGFP(Green Fluorescence Protein)とその改変体を利用して遺伝子工学的に細胞内カルシウム、膜電位などの測定を行う技術を開発する(測定技術の開発)とともに、神経組織由来の初代培養細胞にこれらの遺伝子産物を細胞種特異的なプロモーター(遺伝子の転写調節領域)を利用して発現させて標識し、標識された細胞を差別化して測定を行う(標識技術の開発)ことを目指した。測定技術の開発としては、GFPと既存のカルシウム蛍光色素との間で見られる相互作用に着目して試験管内の検討を行った。その結果、GFPとfura-redもしくはBFP、CFP(blueまたはcyanの蛍光を発するGFPの改変体)とfura-redを共存させた状態においてカルシウム依存的なGFP由来の蛍光の変化が見られた。これはfura-redのカルシウム依存的な吸収スペクトルの変化がGFPの蛍光
    Competitive research funding

  • 文部科学省, 科学研究費補助金(基盤研究(A)), 1996 - 1998
    蛍光Ca2+指示薬による細胞内Ca2+濃度の画像による解析法が利用できるようになって、生細胞内の特定分子のダイナミックな活動様式を可視化を試みる研究に拍車がかかった。というのも、この方法を使えば特定の機能分子の細胞内で、部位特性や活性化時間など新しい情報を提供してくれるからである。このプロジェクトにおいて我々は細胞機能のダイナミックな調節に最も重要な酵素である二種のリン酸化酵素の活性を直接可視化する特異的指示薬を作り出すことおよび微弱な蛍光の変化を確実に解析するシステムを構築することにを目的とした。最初にCa+/カルモデュリン依存性キナ-ゼ(CaMKII)活性の可視化のためにCaMKIIの特異的基質ペプチド、Syntide2のN-末端に蛍光指示薬、Acrylodanを結合させた試薬、AS2を創製し、まず、試験官内でこの試薬がCa2+で活性化されたカルモデュリンとそれによって活性化されるCaMKIIの有効な指示薬になることを確かめた。一方、cAMP依存性キナ-ゼ(PKA)の活性を可
    Competitive research funding

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