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A genetic approach for the understanding of the brain micro-environment that regulates the plasticity of neural stem cells

Research Project

Project/Area Number 17K07116
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionKeio University

Principal Investigator

KANDA Hiroshi  慶應義塾大学, 医学部(信濃町), 講師 (60508597)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsショウジョウバエ / 神経幹細胞 / Neuroblast / 再活性化 / 可塑性 / 遺伝学 / neuroblast / 神経科学
Outline of Final Research Achievements

It has long been reported that adult neural stem cells (NSCs) possess significant plasticity. Interestingly, the plasticity of NSCs is also observed in lower organisms such as invertebrates. We have elucidated the molecular basis of how quiescent neural stem cells are reactivated by using powerful Drosophila genetics. We found that an evolutionarily conserved metabolic enzyme, whose function is required for the lipid metabolism, is required for the proper reactivation of NSCs. We found that this cell death is induced by cholinergic neuron-dependent manner. In addition, the acetylcholine level was increased in the mutant animals. The inhibition of the degradation of acetylcholine also attenuated the reactivation of wild-type quiescent neural stem cells ex vivo.

Academic Significance and Societal Importance of the Research Achievements

成体脳で行われるニューロンの新生は記憶の形成、ストレスからの回復、本能行動などに重要であると考えられており、これが抑制されることで抑鬱などの原因となる事が示唆されている。しかし、発生初期のニューロン新生を経て一旦分裂を休止した神経幹細胞が再活性化する分子機構はこれまでほとんど明らかにされていなかった。我々が本研究によって見出した知見は、上記の課題を解き明かす上で前衛的な知見となり得ると考えられる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (12 results)

All 2020 2019 2018 2017 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Book (1 results) Remarks (3 results)

  • [Journal Article] Degradation of Extracellular Matrix by Matrix Metalloproteinase 2 Is Essential for the Establishment of the Blood-Brain Barrier in Drosophila2019

    • Author(s)
      Hiroshi Kanda, Rieko Shimamura, Michiko Koizumi-Kitajima, Hideyuki Okano
    • Journal Title

      iScience

      Volume: 16 Pages: 218-229

    • DOI

      10.1016/j.isci.2019.05.027

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Evolutionarily conserved molecules regulate the integrity of Blood-Brain Barrier in Drosophila.2019

    • Author(s)
      Hiroshi Kanda, Rieko Shimamura, Michiko Koizumi-Kitajima, Hideyuki Okano
    • Organizer
      第42回日本神経科学大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] A genetic approach for the understanding of the brain micro-environment that regulates the plasticity of neural stem cells.2018

    • Author(s)
      Kanda H, Yamaguchi T, Shimamura R, Sugiura Y, Honda K, Suematsu M, Yoshinari Y, Niwa R, and Okano H.
    • Organizer
      59th Annual Drosophila Research Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 血液脳関門の普遍原理の解析2018

    • Author(s)
      菅田浩司
    • Organizer
      第2回淡路ショウジョウバエ研究会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 脳内微小環境による神経幹細胞の可塑性制御2018

    • Author(s)
      菅田浩司
    • Organizer
      京都大学大学院生命機能研究科 生命科学セミナー
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Brain microenvironment regulates the plasticity of neural stem cells2017

    • Author(s)
      菅田浩司, 島村理恵子, 山口太朗, 北島美智子, 杉浦悠毅, 末松誠, 岡野栄之
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Research-status Report
  • [Presentation] A genetic approach for the understanding of the brain micro-environment that regulates the plasticity of neural stem cells2017

    • Author(s)
      Hiroshi Kanda, Taro Yamaguchi, Rieko Shimamura, Yuki Sugiura, Makoto Suematsu, Hideyuki Okano
    • Organizer
      25th European Drosophila Research Conference
    • Related Report
      2017 Research-status Report
  • [Presentation] 神経幹細胞の可塑性を制御する脳内微小環境の解析2017

    • Author(s)
      菅田浩司
    • Organizer
      第一回淡路ショウジョウバエ研究会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Book] ブレインサイエンス・レビュー20202020

    • Author(s)
      菅田浩司
    • Total Pages
      18
    • Publisher
      クバプロ
    • ISBN
      9784878051647
    • Related Report
      2019 Annual Research Report
  • [Remarks] 岡野研 Weblog

    • URL

      http://www.okano-lab.com/

    • Related Report
      2019 Annual Research Report
  • [Remarks]

    • URL

      http://www.okano-lab.com

    • Related Report
      2018 Research-status Report
  • [Remarks]

    • URL

      http://www.okano-lab.com

    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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