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アストロサイトによる体温調節機序の解明

Publicly Offered Research

Project AreaIntegrative understanding of biological phenomena with temperature as a key theme
Project/Area Number 16H01383
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTokyo Medical and Dental University

Principal Investigator

田中 光一  東京医科歯科大学, 難治疾患研究所, 教授 (80171750)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Keywordsアストロサイト / 体温調節 / グリア
Outline of Annual Research Achievements

体温調節に関与する神経回路に比べ、アストロサイト回路の研究は少ない。我々は、最近、intersectional approachを用い、特定脳領域のアストロサイトのみの細胞内Ca2+濃度を人工リガンドで増加できるツールを開発した。このツールを用い、体温調節に関与するアストロサイトの局在を解析した。視索前野・視床下部背内側部と中隔のアストロサイトのみ(Nkx2.1-Cre)、視床より尾側のアストロサイト(視索前野のアストロサイトは含まないが視床下部背内側部・淡蒼縫線核・脊髄のアストロサイトは含む、foxb1-Cre)のみに、Creが発現しているCreラインとMlc1-tTAマウス (アストロサイト特異的にtTAを発現)及びtetO-FLEX-hM3Dqマウスを交配し、脳部位特異的にhM3Dqをアストロサイトに発現させるマウスを作製した。両マウスの系統にsalineおよびCNO(3mg/kg)を腹腔投与し、投与後の体温変化を測定した。Nkx2.1-Cre/Mlc1-tTA/tetO-FLEX-hM3DqマウスにCNOを投与した時にのみ、体温が約1.5度上昇した。これらの結果は、視索前野(POA)のアストロサイトの活性化が、体温の上昇をもたらすことを示している。さらに、体温上昇を起こしたマウス脳の組織学的解析により、アストロサイトのCa2+濃度上昇によりPOAの抑制性神経細胞および吻側淡蒼縫線核(rRPa)の神経細胞が活性化されていることを見出した。また、これらの領域は、寒冷環境に暴露したマウスにおいて活性化される神経細胞の局在する領域と一致した。本研究の結果は、アストロサイトを介した体温調節の新たなメカニズムの存在を示唆するとともに、体温上昇を司るPOAの神経細胞を同定する大きな足がかりとなる。

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (14 results)

All 2018 2017 2016 Other

All Int'l Joint Research (4 results) Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 9 results,  Open Access: 6 results) Remarks (1 results)

  • [Int'l Joint Research] University of Zurich/Institute of Pharmacology and Toxicology(スイス)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] The University of Edinburgh/Heriot-Watt University(英国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Johns Hopkins University(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Centre for Brain Development and Repair(インド)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Spinal cord-specific deletion of the glutamate transporter GLT1 causes motor neuron death in mice2018

    • 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

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Region-specific deletions of the glutamate transporter GLT1 differentially affect seizure activity and neurodegeneration in mice2017

    • 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

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Calpain-Dependent Degradation of Nucleoporins Contributes to Motor Neuron Death in a Mouse Model of Chronic Excitotoxicity2017

    • 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

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Glutamate transporter GLAST controls synaptic wrapping by Bergmann glia and ensures proper wiring of Purkinje cells2017

    • 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 Issue: 28 Pages: 7438

    • DOI

      10.1073/pnas.1617330114

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of visual Wulst cell responsiveness by imprinting causes stimulus-specific activation of rostral cells.2017

    • Author(s)
      Nakamori T, Kato T, Sakagami H, Tanaka K, Ohki-Hamazaki H.
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 42927-42927

    • DOI

      10.1038/srep42927

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of impaired neuronal migration with cognitive deficits in extremely preterm infants.2017

    • Author(s)
      Kubo K, Deguchi K, Nagai T, Ito Y, Yoshida K, Endo T, Benner S, Shan W, Kitazawa A, Aramaki M, Ishii K, Shin M, Matsunaga Y, Hayashi K, Kakeyama M, Tohyama C, Tanaka KF, Tanaka K, Takashima S, Nakayama M, Itoh M, Hirata Y, Antalffy B, Armstrong DD, Yamada K, Inoue K, Nakajima K
    • Journal Title

      JCI Insight

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Posterior cerebellar Purkinje cells in an SCA5/SPARCA1 mouse model are especially vulnerable to the synergistic effect of loss of β-III spectrin and GLAST.2016

    • Author(s)
      Perkins EM, Suminaite D, Clarkson YL, Lee SK, Lyndon AR, Rothstein JD, Wyllie DJ, Tanaka K, Jackson M.
    • Journal Title

      Hum Mol Genet.

      Volume: 25 Pages: 4448-4461

    • DOI

      10.1093/hmg/ddw274

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of geranylgeranylacetone on the protection of retinal ganglion cells in a mouse model of normal tension glaucoma.2016

    • Author(s)
      Dong Z, Shinmei Y, Dong Y, Inafuku S, Fukuhara J, Ando R, Kitaichi N, Kanda A, Tanaka K, Noda K, Harada T, Chin S, Ishida S.
    • Journal Title

      Heliyon

      Volume: 2 Issue: 10 Pages: e00191-e00191

    • DOI

      10.1016/j.heliyon.2016.e00191

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gene cassette knock-in in mammalian cells and zygotes by enhanced MMEJ.2016

    • Author(s)
      Aida T, Nakade S, Sakuma T, Izu Y, Oishi A, Mochida K, Ishikubo H, Usami T, Aizawa H, Yamamoto T, Tanaka K.
    • Journal Title

      BMC Genomics

      Volume: 17 Issue: 1 Pages: 979-979

    • DOI

      10.1186/s12864-016-3331-9

    • Related Report
      2016 Annual Research Report
    • 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

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2016-04-26   Modified: 2022-01-31  

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