Neurological and psychiatric research using adenosine sensor cells

• Project/Area Number: 17K07110
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kobe University
• Principal Investigator: Morita Mitsuhiro 神戸大学, 理学研究科, 准教授 (50297602)
• Project Period (FY): 2017-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: アデノシン / ドーパミン / 双極性障害 / 水チャネル / アストロサイト / 脳傷害 / 精神疾患 / AQP4 / うつ / ストレス障害 / バイオセンサー / イメージング / 神経科学 / 生理学 / 脳・神経 / 脳神経疾患 / 薬理学

Outline of Final Research Achievements

We examined the relationship between the water channel AQP4-dependent astrocyte adenosine release found in previous studies and the modulation of dopamine neurotransmission following cocaine administration. We found that the acute-phase arousal effects of cocaine and depressive-like behavior as a withdrawal symptom were abolished in AQP4-deficient mice. In addition, measurements of adenosine or dopamine release in striatal slices revealed that cocaine withdrawal causes a upregulation of AQP4-dependent adenosine increase and a concomitant decrease in dopamine release. These results are the first to demonstrate that modulation of AQP4-dependent adenosine release underlies psychiatric disorders.

Academic Significance and Societal Importance of the Research Achievements

アストロサイトが水 チャンネルAQP4を発現することは広く知られているが、その役割については不明な点が多く残されていた。 本研究によりAQP4が神経修飾因子アデノシンを放出する機序の一部であり、これが変化することにより、ドーパミン神経伝達の変調と精神疾患が引き起こされることが初めて明らかとなった。これは脳における水の循環と神経細胞による情報処理という、一見無関係に見える現象が相互作用することを示しており、脳における機能調節と病態について全く新しい視点をもたらしたと言える。

Research Products

• [Int'l Joint Research] リュブリャナ大学(スロベニア)
• [Int'l Joint Research] University of Ljubljana(スロベニア)
• [Journal Article] Incomplete accumulation of perilesional reactive astrocytes exacerbates wound healing after closed-head injury by increasing inflammation and BBB disruption (2024)
  • Author(s): Sawant Nitin、Watanabe Airi、Ueda Haruna、Okano Hideyuki、Morita Mitsuhiro
  • Journal Title: Experimental Neurology Volume: 374 Pages: 114700-114700
  • DOI: 10.1016/j.expneurol.2024.114700
  • Peer Reviewed / Open Access
• [Journal Article] 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 (2023)
  • Author(s): 的場修，森田光洋
  • Journal Title: 光技術コンタクト Volume: 61 Pages: 20-24
• [Journal Article] Modern Microscopic Approaches to Astrocytes (2023)
  • Author(s): Morita Mitsuhiro
  • Journal Title: International Journal of Molecular Sciences Volume: 24 Issue: 6 Pages: 5883-5883
  • DOI: 10.3390/ijms24065883
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation and Manipulation of Neural Activity using Two-Photon Holographic Microscopy (2022)
  • Author(s): Kato Daisuke、Quan Xiangyu、Tanisumi Yuta、Guo Zhongtian、Morita Mitsuhiro、Takiguchi Tetsuya、Matoba Osamu、Wake Hiroaki
  • Journal Title: Journal of Visualized Experiments Volume: 187 Issue: 187 Pages: 1-15
  • DOI: 10.3791/64205
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Quantitative dynamic evolution of physiological parameters of RBC by highly stable digital holographic microscopy (2022)
  • Author(s): Kumar Manoj、Matoba Osamu、Quan Xiangyu、Rajput Sudheesh K、Morita Mitsuhiro、Awatsuji Yasuhiro
  • Journal Title: Optics and Lasers in Engineering Volume: 151 Pages: 106887-106887
  • DOI: 10.1016/j.optlaseng.2021.106887
  • Peer Reviewed / Open Access
• [Journal Article] Effects of leptin on proliferation of astrocyte- and tanycyte-like neural stem cells in the adult mouse medulla oblongata. (2021)
  • Author(s): Nambu Y, Ohira K, Morita M, Yasumoto H, Kurganov E, Miyata S.
  • Journal Title: Neuroscience Research Volume: 173 Pages: 44-53
  • DOI: 10.1016/j.neures.2021.05.012
  • Peer Reviewed / Open Access
• [Journal Article] 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 (2021)
  • Author(s): 森田光洋、安井正人
  • Journal Title: 実験医学（増刊号）「神経免疫 メカニズムと疾患」 Volume: 39 Pages: 2399-2402
• [Journal Article] The Diversity of Intermediate Filaments in Astrocytes (2020)
  • Author(s): Potokar Maja、Morita Mitsuhiro、Wiche Gerhard、Jorga?evski Jernej
  • Journal Title: Cells Volume: 9 Issue: 7 Pages: 1604-1604
  • DOI: 10.3390/cells9071604
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neural stem cell phenotype of tanycyte-like ependymal cells in the circumventricular organs and central canal of adult mouse brain (2020)
  • Author(s): Furube Eriko、Ishii Haruna、Nambu Yuri、Kurganov Erkin、Nagaoka Sumiharu、Morita Mitsuhiro、Miyata Seiji
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 1-1
  • DOI: 10.1038/s41598-020-59629-5
  • Peer Reviewed / Open Access
• [Journal Article] Three-dimensional fluorescence imaging using the transport of intensity equation (2019)
  • Author(s): Rajput Sudheesh K.、Kumar Manoj、Quan Xiangyu、Morita Mitsuhiro、Furuyashiki Tomoyuki、Awatsuji Yasuhiro、Tajahuerce Enrique、Matoba Osamu
  • Journal Title: Journal of Biomedical Optics Volume: 25 Issue: 03 Pages: 1-1
  • DOI: 10.1117/1.jbo.25.3.032004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] VEGF- and PDGF-dependent proliferation of oligodendrocyte progenitor cells in the medulla oblongata after LPC-induced focal demyelination. (2019)
  • Author(s): Hiratsuka D, Kurganov E, Furube E, Morita M, Miyata S.
  • Journal Title: Journal of Neuroimmunoogy Volume: 332 Pages: 176-186
  • DOI: 10.1016/j.jneuroim.2019.04.016
  • Peer Reviewed
• [Journal Article] Metabolic Plasticity of Astrocytes and Aging of the Brain (2019)
  • Author(s): Morita Mitsuhiro、Ikeshima-Kataoka Hiroko、Kreft Marko、Vardjan Nina、Zorec Robert、Noda Mami
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 4 Pages: 941-941
  • DOI: 10.3390/ijms20040941
  • NAID: 120006599242
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Inhibitory effect of several sphingolipid metabolites on calcineurin (2018)
  • Author(s): Maruyama Yoko、Ueno Satoko、Morita Mitsuhiro、Hayashi Fumio、Maekawa Shohei
  • Journal Title: Neuroscience Letters Volume: 673 Pages: 132-135
  • DOI: 10.1016/j.neulet.2018.03.010
  • Peer Reviewed
• [Journal Article] Interaction of dynamin I with NAP-22, a neuronal protein enriched in the presynaptic region (2018)
  • Author(s): Ueno Satoko、Miyoshi Hiroshi、Maruyama Yoko、Morita Mitsuhiro、Maekawa Shohei
  • Journal Title: Neuroscience Letters Volume: 675 Pages: 59-63
  • DOI: 10.1016/j.neulet.2018.03.061
  • Peer Reviewed
• [Journal Article] Remyelination in the medulla oblongata of adult mouse brain during experimental autoimmune encephalomyelitis (2018)
  • Author(s): Hiratsuka Daishi、Furube Eriko、Taguchi Katsutoshi、Tanaka Masaki、Morita Mitsuhiro、Miyata Seiji
  • Journal Title: Journal of Neuroimmunology Volume: 319 Pages: 41-54
  • DOI: 10.1016/j.jneuroim.2018.03.014
  • Peer Reviewed / Open Access
• [Journal Article] Microglia are continuously activated in the circumventricular organs of mouse brain. (2017)
  • Author(s): Takagi S, Furube E, Nakano Y, Morita M, Miyata S.
  • Journal Title: Journal of Neuroimmunology Volume: S0165-5728 Pages: 30384-3
  • DOI: 10.1016/j.jneuroim.2017.10.008
  • Peer Reviewed
• [Journal Article] Astrocyte calcium waves propagate proximally by gap junction and distally by extracellular diffusion of ATP released from volume-regulated anion channels (2017)
  • Author(s): Fujii Yuki、Maekawa Shohei、Morita Mitsuhiro
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 13115-13115
  • DOI: 10.1038/s41598-017-13243-0
  • NAID: 120006358588
  • Peer Reviewed / Open Access
• [Journal Article] Novel aspects of extracellular adenosine dynamics revealed by adenosine sensor cells (2017)
  • Author(s): Morita Mitsuhiro、Yamashiro Kunihiko
  • Journal Title: Neural Regeneration Research Volume: 12 Issue: 6 Pages: 881-881
  • DOI: 10.4103/1673-5374.208544
  • NAID: 120006358587
  • Peer Reviewed / Open Access
• [Presentation] Holographic microscope free from nonspecific opsin activation by imaging laser, “crosstalk” (2023)
  • Author(s): Priyanka Gore, Yuya Atomura, Manoj Kumar, Xiangyu Quan, Osamu Matoba, Hiroaki Wake, Mitsuhiro Morita
  • Organizer: 第46回日本神経科学会
• [Presentation] Impaired recovery from focal closed-head injury by STAT3 ablation in perilesional reactive astrocyte (2023)
  • Author(s): Sawant Nitin, Morita Mitsuhiro
  • Organizer: 第46回日本神経科学会
• [Presentation] Analysis of Local Intracellular Signaling in Astrocytes Using Two-Photon Holographic Microscopy (2023)
  • Author(s): M. Morita, Y. Atomura, P. Gora, M. Kumar, X. Quan, O. Matoba, H. Wake
  • Organizer: European Meeting on Glial Cells in Health and Disease
  • Int'l Joint Research
• [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 (2023)
  • Author(s): 的場修，森田光洋
  • Organizer: 第99回レーザー加工学会
  • Invited
• [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 (2022)
  • Author(s): 森田光洋
  • Organizer: 第96回日本薬理学会
  • Invited
• [Presentation] Emotional arousal enhances perceptual memory through amygdalo-cortical input during NREM sleep (2022)
  • Author(s): Yoshihito Saito,Yuma Osako,Maya Odagawa,Yasuhiro Oisi,Chie Matsubara,Mitsuhiro Morita,Masanori Murayama
  • Organizer: 第45回日本神経科学会
• [Presentation] Cortical-wide impairment of “the Glymphatic System” after focal brain injury (2022)
  • Author(s): Lee, H,Azuma, M,Shinzaki, K,Yamane, R,Morita, M
  • Organizer: 第45回日本神経科学会
• [Presentation] Effects of fingolimod on vasculature and glial scar formation after closed-head injury (2022)
  • Author(s): Sawant, N,Okazaki, N,Morita, M
  • Organizer: 第45回日本神経科学会
• [Presentation] Crosstalk between AQP4-dependent ATP/Adenosine release and dopamine system in cocaine-induced depressive behavior (2021)
  • Author(s): Morita, M., Okada, S. and Kobayashi, M.
  • Organizer: 第44回日本神経科学会
• [Presentation] Upregulated glutamate response and oscillation of [Ca2+]i increases of perilesional reactive astrocyte after closed-head injury (2020)
  • Author(s): Ueda, H and Morita, M.
  • Organizer: 第43回日本神経科学会
• [Presentation] Mesenchymal stem cell promotes sphere-formation and de-differentiation of astrocytes (2020)
  • Author(s): Sunhwa, G., Saito, Y. and Morita, M.
  • Organizer: 第43回日本神経科学会
• [Presentation] ATP/Adenosine release and dopamine system in cocaine-induced depressive behavior (2020)
  • Author(s): Morita, M., Okada, S. and Kobayashi, M.
  • Organizer: 第43回日本神経科学会
• [Presentation] Glial scar formation by reactive astrocytes derived from oligodendrocyte progenitor cells (2019)
  • Author(s): Matsuda, H., Ueda, H., Tsuji, E. and Morita
  • Organizer: NEURO2019
• [Presentation] AQP4-dependent increase of extracellular ATP/Adenosine regulates dopaminergic neurotransmission in the striatum (2019)
  • Author(s): Okada, S., Kobayashi, M. and Morita, M.
  • Organizer: NEURO2019
• [Presentation] AQP4-dependent increase of extracellular ATP/Adenosine derived from astrocytes regulates dopaminergic neurotransmission in the striatum (2019)
  • Author(s): Morita, M., Kobayashi, M. and Okada, S.
  • Organizer: XIV European Meeting on Glial Cells in Health and Disease
  • Int'l Joint Research
• [Presentation] Widespread impairment of cerebrospinal fluid flow in a focal closed-head injury model, photo-injury mouse (2018)
  • Author(s): Morita, M., and Azuma
  • Organizer: Cold Spring Harber Asia
  • Int'l Joint Research / Invited
• [Presentation] Multiple pathways for ATP/adenosine release in the brain (2018)
  • Author(s): Morita, M.
  • Organizer: NEVROGLIJA V NORMALNIH IN PATOLOŠKIH RAZMERAH
  • Int'l Joint Research / Invited
• [Presentation] Widespread impairment of glymphatic flow in a focal closed head injury model, photo-injury mouse (2018)
  • Author(s): Azuma, M. and Morita, M.
  • Organizer: 日本神経科学会
• [Presentation] Widespread impairment of glymphatic flow in a focal closed-head injury model, photo-injury mouse (2018)
  • Author(s): Morita, M., and Masae, A.
  • Organizer: FENS Meeting
• [Presentation] Generation of new oligodendrocytes in the medulla oblongata of mice by EAE-induced demyelination (2017)
  • Author(s): Hiratsuka, D., Furube, E., Morita, M., Miyata S.
  • Organizer: 第40回 日本神経科会
• [Presentation] Multiple origins of perilesional nestin-expressing reactive astrocytes following closed-head injury (2017)
  • Author(s): Morita, M. Okazaki, N, Tsuji, E.
  • Organizer: 第40回 日本神経科会
• [Presentation] Localization of neural stem cells and stroke-induced generation of new neurons and glia in the medulla oblongata (2017)
  • Author(s): Furube, E., Hiratsuka, D., Taguchi, K., Tanaka, M., Morita, M., Miyata, S.
  • Organizer: 第40回 日本神経科会
• [Presentation] Bone marrow derived mesenchymal stem cells promote the multipotency of nestin-expressing reactive astrocytes (2017)
  • Author(s): Saito, Y., Morita, M.
  • Organizer: 第40回 日本神経科会
• [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 (2017)
  • Author(s): 森田光洋、岡崎夏樹、松田ひなた、辻恵里佳
  • Organizer: 第60回 日本脳循環代謝学会
• [Presentation] 骨髄間葉系幹細胞によるアストロサイトの多分可能促進 (2017)
  • Author(s): 齋藤喜仁、森田光洋
  • Organizer: 第60回 日本脳循環代謝学会
• [Presentation] MULTIPLE ORIGINS OF PERILESIONAL NESTIN-EXPRESSING REACTIVE ASTROCYTES FOLLOWING CLOSED-HEAD INJURY (2017)
  • Author(s): Morita, M., Okazaki, N., Tsuji, E.
  • Organizer: International Society for Neurochemistry
  • Int'l Joint Research
• [Book] 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 (2022)
  • Author(s): 的場 修,全 香玉,米田 成,森田 光洋
  • Total Pages: 643
  • Publisher: 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