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Search for the origin of adult neural stem cell and analysis of granule cell layer formation in the dentate gyrus

Research Project

Project/Area Number 16K18983
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General anatomy (including histology/embryology)
Research InstitutionTokyo Medical University

Principal Investigator

Shinohara Hiroshi  東京医科大学, 医学部, 講師 (10455793)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords神経幹細胞 / 海馬 / 歯状回 / 顆粒細胞層 / 電気穿孔法 / ニューロン新生 / 海馬歯状回 / 顆粒細胞 / in utero electroporation / 成体期海馬神経幹細胞 / 海馬歯状回顆粒細胞 / 子宮内電気穿孔法 / ライムラプス観察
Outline of Final Research Achievements

In general, neurogenesis occurs during embryonic and early postnatal stages, and ceases at adult stage. However, the dentate gyrus (DG) continues neurogenesis from embryonic to adult stages.
We focused on the origin of adult neural stem cells and the forming pattern of granule cell layer in the dentate gyrus. In the early stage, we found that adult neural stem cells born in dorsal dentate notch. Moreover, it is observed that granule cells are distributed at the molecular layer side. These data indicate that dorsal origin adult neural stem cells born at the early stage and granule cell accumulate in an outside-in sequence.

Academic Significance and Societal Importance of the Research Achievements

海馬歯状回の成体期ニューロン新生を引き起こす神経幹細胞の起源および顆粒細胞の形成過程を明らかにすることは、研究が盛んな成体脳ニューロン新生の研究分野と胎生期のニューロン新生研究とを結び合わせることを可能とし、まさに『ゆりかごから墓場まで』の海馬形成の理解が深まり、新たな研究分野創成といった面でも非常に意義がある。
さらに本研究を通じた、他の脳領域と異なり海馬が成体までニューロン新生を継続できるメカニズムが解明は、成体ではニューロン新生が生じない他の神経領域において、ニューロン新生を意図的に生じさせることが可能となる。これを活用すれば、失われた中枢神経系を復活させる再生医療への発展にも繋がる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (14 results)

All 2020 2019 2018 2017

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

  • [Journal Article] The polarity and properties of radial glia-like neural stem cells are altered by seizures with status epilepticus: Study using an improved mouse pilocarpine model of epilepsy2020

    • Author(s)
      Sasaki-Takahashi N, Shinohara H, Shioda S, Seki T.
    • Journal Title

      Hippocampus

      Volume: 30 Issue: 3 Pages: 250-262

    • DOI

      10.1002/hipo.23153

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Non-radial tortuous migration with cell polarity alterations of newly generated granule neurons in the neonatal rat dentate gyrus2019

    • Author(s)
      Namba T, Shinohara H, Seki T
    • Journal Title

      Brain Struct Funct

      Volume: 224 Issue: 9 Pages: 3247-3262

    • DOI

      10.1007/s00429-019-01971-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 1次繊毛形成の正常化はダウン症候群の治療標的に成り得るか?2019

    • Author(s)
      篠原 広志
    • Journal Title

      ファルマシア

      Volume: 55 Pages: 703-703

    • NAID

      130007671673

    • Related Report
      2019 Annual Research Report
  • [Journal Article] The role of Pax6 in brain development and its impact on pathogenesis of autism spectrum disorder2018

    • Author(s)
      Kikkawa Takako、Casingal Cristine R.、Chun Seung Hee、Shinohara Hiroshi、Hiraoka Kotaro、Osumi Noriko
    • Journal Title

      Brain Research

      Volume: - Pages: 30111-2

    • DOI

      10.1016/j.brainres.2018.02.041

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dynamics and function of CXCR4 in formation of the granule cell layer during hippocampal development2017

    • Author(s)
      Miura-Yamamoto Y, Shinohara H, Kashiwagi T, Sato T, Shioda S, Seki T
    • Journal Title

      Scientific Reports

      Volume: 7: 5647 Issue: 1 Pages: 1-14

    • DOI

      10.1038/s41598-017-05738-7

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 顆粒細胞形成におけるTbr2の機能および顆粒細胞サブタイプ解析2020

    • Author(s)
      篠原 広志, 石 龍徳
    • Organizer
      第16回 成体脳ニューロン新生懇談会・「個性」創発脳共催研究会in仙台2020
    • Related Report
      2019 Annual Research Report
  • [Presentation] Tbr2依存/非依存性ニューロン解析から紐解く時空間的な海馬の形成メカニズム2020

    • Author(s)
      篠原 広志, 石 龍徳
    • Organizer
      第125回 日本解剖学会総会・全国学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 成体期海馬神経幹細胞の起源探索および海馬歯状回顆粒細胞層形成メカニズムの解析2019

    • Author(s)
      篠原 広志, 石 龍徳
    • Organizer
      第42回 日本神経科学大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Gfap-GFPマウスを用いた発生過程における海馬歯状回形成細胞の移動解析2018

    • Author(s)
      篠原 広志、石 龍徳
    • Organizer
      第41回 日本神経科学大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Two distinctive dorsal and ventral pathways form dentate granule cell layer2018

    • Author(s)
      篠原 広志、石 龍徳
    • Organizer
      第124回 日本解剖学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 海馬歯状回顆粒細胞形成の分子メカニズム解析2018

    • Author(s)
      篠原広志、石 龍徳
    • Organizer
      第123回 日本解剖学会総会・全国学術集会(武蔵境)
    • Related Report
      2017 Research-status Report
  • [Presentation] 海馬歯状回のつくられ方:神経前駆細胞の発生過程に依存した移動パターン変化2017

    • Author(s)
      篠原広志
    • Organizer
      第2回 春の神経発生研究会(東北大学)
    • Related Report
      2017 Research-status Report
  • [Presentation] 海馬顆粒細胞は発生時期に応じて異なる経路に依存したタイプの異なる細胞によって形成される2017

    • Author(s)
      篠原広志、石 龍徳
    • Organizer
      第40回 日本神経科学大会(幕張メッセ)
    • Related Report
      2017 Research-status Report
  • [Presentation] 子宮内電気穿孔法による海馬歯状回メカニズムの解析2017

    • Author(s)
      篠原広志、 石 龍徳
    • Organizer
      第39回神経組織培養研究会・企業セミナー(名古屋)
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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