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Molecular mechanism of neuronal network regeneration in the adult mouse brain

Research Project

Project/Area Number 16H04672
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionNational Center of Neurology and Psychiatry (2018)
Osaka University (2016-2017)

Principal Investigator

Muramatsu Rieko  国立研究開発法人国立精神・神経医療研究センター, 神経研究所 神経薬理研究部, 部長 (90536880)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords多発性硬化症 / 髄鞘 / 神経回路 / 脱髄 / 血液脳関門 / 白質 / 細胞増殖 / 脊髄 / オリゴデンドロサイト / ミエリン
Outline of Final Research Achievements

Central nervous system (CNS) inflammation causes disruption of neuronal network, resulting in cause severe neurological dysfunction. Although it has been believed that neuronal network in the CNS can not regenerate in adult mammalians, recent studies observe the spontaneous regeneration of the neuronal network in the CNS, indicating that neural cells in the adult CNS still has the potential to regenerate against injury. Due to the understand the mechanism of spontaneous regeneration, we focused on the vascular disruption, which is a promising feature around the lesion, and found that the molecules which drive CNS regeneration contain the circulation. We revealed that circulating factors leaks into the CNS in the response to CNS injury, resulting in promotes CNS remyelination. These results give the circulating molecules a role for regulation of CNS regeneration.

Academic Significance and Societal Importance of the Research Achievements

脳の神経回路の修復研究は、脳の内部の細胞や分子の働きを理解する形で知見が積み上げられている。一方、病態では、病巣周囲で血管のバリア機能が破綻し、血液が脳に流入しやすい状態になっている。血液には、種々の生理活性物質が含まれているが、血液の脳内への流入が神経回路の修復にいかなる影響を与えるかは不明であった。本研究は、血液を介して、脳以外の臓器が脳神経回路の修復を制御するという新しい知見を示すものであり、神経回路の修復研究に新しい方向性を示すものである。また、得られた分子メカニズムは、神経回路の修復により症状改善が見込める種々の疾患の治療薬のシーズとなるポテンシャルもあり、臨床的にも意義深い。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (18 results)

All 2019 2018 2017 2016 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 5 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) (of which Int'l Joint Research: 1 results,  Invited: 7 results) Remarks (1 results)

  • [Journal Article] Circulating transforming growth factor-β1 facilitates remyelination in the adult central nervous system2019

    • Author(s)
      Hamaguchi Machika、Muramatsu Rieko、Fujimura Harutoshi、Mochizuki Hideki、Kataoka Hirotoshi、Yamashita Toshihide
    • Journal Title

      eLife

      Volume: 8

    • DOI

      10.7554/elife.41869

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Myotube-derived factor promotes oligodendrocyte precursor cell proliferation2018

    • Author(s)
      Akino Nakasone, Rieko Muramatsu, Yuki Kato, Yukio Kawahara and Toshihide Yamashita
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 500 Issue: 3 Pages: 609-613

    • DOI

      10.1016/j.bbrc.2018.04.118

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extracellular Lactate Dehydrogenase A Release From Damaged Neurons Drives Central Nervous System Angiogenesis.2018

    • Author(s)
      Lin H, Muramatsu R, Maedera N, Tsunematsu H, Hamaguchi M, Koyama Y, Kuroda M, Ono K, Sawada M, Yamashita T.
    • Journal Title

      EBioMedicine

      Volume: 27 Pages: 71-85

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Peripherally derived FGF21 promotes remyelination in the central nervous system.2017

    • Author(s)
      Kuroda M, Muramatsu R, Maedera N, Koyama Y, Hamaguchi M, Fujimura H, Yoshida M, Konishi M, Itoh N, Mochizuki H, Yamashita T.
    • Journal Title

      J Clin Invest.

      Volume: 127 Issue: 9 Pages: 3496-3509

    • DOI

      10.1172/jci94337

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Leptin sustains spontaneous remyelination in the adult central nervous system.2017

    • Author(s)
      Matoba, K., Muramatsu, R. and Yamashita, T.
    • Journal Title

      Sci. Rep.

      Volume: 7 Issue: 1 Pages: 40397-40397

    • DOI

      10.1038/srep40397

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cardiomyocyte-released factors stimulate oligodendrocyte precursor cells proliferation.2016

    • Author(s)
      Kuroda, M., Muramatsu, R., and Yamashita, T.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 482 Issue: 4 Pages: 1160-1164

    • DOI

      10.1016/j.bbrc.2016.12.004

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] The role of Fibroblast growth factor 21 in the development of schwann cell line.2019

    • Author(s)
      村松里衣子、石井智裕
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脳神経回路の傷害と修復を司る生体システムの解明2019

    • Author(s)
      村松里衣子
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Neurovascular interaction is required for central nervous system regeneration.2018

    • Author(s)
      村松里衣子
    • Organizer
      第61回日本神経化学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 中枢神経回路の修復機構における多臓器円環の意義2018

    • Author(s)
      村松里衣子
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Peripheral environment regulates remyelination in the adult CNS.2017

    • Author(s)
      村松里衣子、山下俊英
    • Organizer
      Neuroscience Network in Kobe Symposium
    • Place of Presentation
      神戸
    • Year and Date
      2017-02-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] バルーン閉塞試験における血中タンパク質変動の検討~プロテオミクス解析を用いた網羅的解析も含めて~2017

    • Author(s)
      尾崎友彦、村松里衣子、木下学、中村元、貴島晴彦、山下俊英
    • Organizer
      第33回日本脳神経血管内治療学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脳と脊髄の神経回路の修復メカニズム2017

    • Author(s)
      村松里衣子、山下俊英
    • Organizer
      第516回東北大学大学院薬学研究科セミナー
    • Related Report
      2017 Annual Research Report
  • [Presentation] 一過性脳虚血におけるオステオポンチン発現の検証 ~基礎研究結果のヒトでの検証~2017

    • Author(s)
      尾崎友彦、村松里衣子、木下学、中村元、吉峰俊樹、貴島晴彦、山下俊英
    • Organizer
      第18回日本分子脳神経外科学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 中枢神経系の恒常性維持機構と神経-血管相互作用2017

    • Author(s)
      村松里衣子、山下俊英
    • Organizer
      第7回細胞再生医療研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Peripheral environment is involved in central nervous system2017

    • Author(s)
      Muramatsu, R., Yamashita, T.
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Central nervous system regeneration2017

    • Author(s)
      Muramatsu, R., Yamashita, T.
    • Organizer
      Satellite Interstellar Initiative at A*STAR
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] https://www.hs.ura.osaka-u.ac.jp/muramatsurieko/

    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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