Circuit-specific neuron-astrocyte cross-talk in the striatum

• Project/Area Number: 17H02216
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Basic / Social brain science
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Tanaka Kohichi 東京医科歯科大学, 難治疾患研究所, 教授 (80171750)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: アストロサイト / 線条体 / 直接路 / 間接路 / ゲノム編集

Outline of Final Research Achievements

Astrocytes were thought as passive support cells, bringing nutrients to and removing wastes form the neurons. Recent studies challenged this view and demonstrated that astrocyte plays a critical role in information processing in the brain. However, it is unclear how astrocyte is involved in higher brain functions. In this study, we focused on the basal ganglia and identified specific marker genes of striatal astrocytes that are associated with direct and indirect pathways. The combination of these marker genes and genome editing techniques will accelerate the elucidation of circuit-specific functions of astrocytes.

Academic Significance and Societal Importance of the Research Achievements

本研究により、アストロサイトの各サブタイプが特定の神経回路において果たす役割の解明が促進され、アストロサイトの機能制御による脳機能制御という新しい研究分野を開拓できる。さらに、本研究は、アストロサイトの異常が示唆されているハンチントン病・アルツハイマー病・パーキンソン病・筋萎縮性側索硬化症などの神経変性疾患やうつ病・自閉症・統合失調症などの精神疾患の病態解明及び新規治療薬の開発に貢献すると期待される。

Research Products

• [Int'l Joint Research] The University of Edinburgh/Heriot-Watt University(英国)
• [Int'l Joint Research] Johns Hopkins University(米国)
• [Int'l Joint Research] Institute for stem cell biology(インド)
• [Int'l Joint Research] Karolinska Institute(スウェーデン)
• [Int'l Joint Research] University of Zurich/Institute of Pharmacology and Toxicology(スイス)
• [Journal Article] Establishment of a tTA-dependent photoactiveatable Cre recombinease knock-in mouse model for optogenetic genome engineering. (2020)
  • Author(s): 9.Takao, T., Hiraoka, Y., Kawabe, K., Yamada, D., Ming, L., Tanaka, K., Sato, M., Takarada, T.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 526 Issue: 1 Pages: 213-217
  • DOI: 10.1016/j.bbrc.2020.03.015
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Functional roles of glial glutamate transporter (GLAST) in emotional and cognitive abnormalities of mice after repeated phencyclidine administration. (2019)
  • Author(s): chida, M., Hida, H., Mori, K., Yoshimi, A., Kitagaki, S., Yamada, K., Hiraoka, Y., Aida, T., Tanaka, K., Ozaki, N., Noda, Y.
  • Journal Title: European Neuropsychopharmacology Volume: 29 Issue: 8 Pages: 914-924
  • DOI: 10.1016/j.euroneuro.2019.06.005
  • Peer Reviewed / Open Access
• [Journal Article] Biased genome editing using the local accumulation of DSB repair molecules system. (2018)
  • Author(s): Nakade S, Mochida K, Kunii A, Nakamae K, Aida T, Tanaka K, Sakamoto N, Sakuma T, Yamamoto T
  • Journal Title: Nature Communications Volume: 9(1) Issue: 1 Pages: 3270-3270
  • DOI: 10.1038/s41467-018-05773-6
  • Peer Reviewed / Open Access
• [Journal Article] Loss of cerebellar glutamate transporters EAAT4 and GLAST differentially affects the spontaneous firing pattern and survival of Purkinje cells (2018)
  • Author(s): Perkins Emma M、Clarkson Yvonne L、Suminaite Daumante、Lyndon Alastair R、Tanaka Kohichi、Rothstein Jeffrey D、Skehel Paul A、Wyllie David J A、Jackson Mandy
  • Journal Title: Human Molecular Genetics Volume: 27 Issue: 15 Pages: 2614-2627
  • DOI: 10.1093/hmg/ddy169
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Region-specific deletions of the glutamate transporter GLT1 differentially affect nerve injury-induced neuropathic pain in mice (2018)
  • Author(s): Zhao Zhuoyang、Hiraoka Yuichi、Ogawa Hiroshi、Tanaka Kohichi
  • Journal Title: Glia Volume: 66 Issue: 9 Pages: 1988-1998
  • DOI: 10.1002/glia.23452
  • Peer Reviewed
• [Journal Article] Glutamate transporter Slc1a3 mediates inter‐niche stem cell activation during skin growth (2018)
  • Author(s): Reichenbach Bettina、Classon Johanna、Aida Tomomi、Tanaka Kohichi、Genander Maria、G?ritz Christian
  • Journal Title: The EMBO Journal Volume: 37 Issue: 9
  • DOI: 10.15252/embj.201798280
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Spinal cord-specific deletion of the glutamate transporter GLT1 causes motor neuron death in mice (2018)
  • Author(s): Sugiyama Kaori、Tanaka Kohichi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 497 Issue: 2 Pages: 689-693
  • DOI: 10.1016/j.bbrc.2018.02.132
  • Peer Reviewed
• [Journal Article] Region-specific deletions of the glutamate transporter GLT1 differentially affect seizure activity and neurodegeneration in mice (2017)
  • Author(s): Sugimoto Junya、Tanaka Moeko、Sugiyama Kaori、Ito Yukiko、Aizawa Hidenori、Soma Miho、Shimizu Tomoko、Mitani Akira、Tanaka Kohichi
  • Journal Title: Glia Volume: 66 Issue: 4 Pages: 777-788
  • DOI: 10.1002/glia.23281
  • Peer Reviewed
• [Journal Article] Calpain-Dependent Degradation of Nucleoporins Contributes to Motor Neuron Death in a Mouse Model of Chronic Excitotoxicity (2017)
  • Author(s): Sugiyama Kaori、Aida Tomomi、Nomura Masatoshi、Takayanagi Ryoichi、Zeilhofer Hanns U.、Tanaka Kohichi
  • Journal Title: The Journal of Neuroscience Volume: 37 Issue: 36 Pages: 8830-8844
  • DOI: 10.1523/jneurosci.0730-17.2017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Glutamate transporter GLAST controls synaptic wrapping by Bergmann glia and ensures proper wiring of Purkinje cells. (2017)
  • Author(s): Miyazaki T, Yamasaki M, Hashimoto K, Kohda K, Yuzaki M, Shimamoto K, Tanaka K, Kano M, Watanabe M.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 114(28) Issue: 28 Pages: 7438-7443
  • DOI: 10.1073/pnas.1617330114
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Remarks] 分子神経科学分野
  • URL: http://www.tmd.ac.jp/mri/aud/index.html