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The role of microglia in aberrant synaptic remodeling induced by peripheral nerve injury

Research Project

Project/Area Number 16K18995
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General physiology
Research InstitutionTokyo Women's Medical University

Principal Investigator

Ueta Yoshifumi  東京女子医科大学, 医学部, 助教 (00511015)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords体性感覚 / 脳幹 / 視床 / ミクログリア / シナプス / 神経損傷 / マウス / 生理学 / 脳・神経 / 神経科学
Outline of Final Research Achievements

Peripheral nerve injury rapidly reorganizes somatotopic maps in the adult brain. In mice, whisker deafferentation induces synaptic remodeling of ascending fibers on neurons in the barreloids of the ventral posteromedial (VPM) nucleus. VPM neurons receive multiple fibers derived not only from whisker but also from non-whisker regions of the brainstem, resulting in reorganized whisker map. However, it is unclear what mechanisms regulate this aberrant plasticity. Here I examine the involvement of microglia which are associated with formation and refinement of synapses. Microglial activity was increased in the whisker sensory pathway after the nerve injury. I found that the depletion of microglia suppressed nerve injury-induced synaptic remodeling in VPM.

Academic Significance and Societal Importance of the Research Achievements

末梢神経の損傷は神経障害性疼痛や感覚機能の異常を引き起こし、これらに対する根本的治療法はいまだ確立されていない。これまでの多くの研究で、脳の感覚神経伝導路が可塑的な改編を受けることが、機能的な異常に重要な役割を果たすと考えられてきた。本研究は動物モデルを用いて詳細な回路機能を調べ、神経損傷に伴う体性感覚経路の改編を抑制する手段を見出した。この成果をさらに進展させることで、将来的には神経損傷に伴う機能異常を抑制する治療法の開発につながることが期待される。

Report

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

    (12 results)

All 2019 2018 2017 2016

All Journal Article (3 results) Presentation (9 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] 神経損傷に伴う中枢回路の再構築2018

    • Author(s)
      植田禎史
    • Journal Title

      細胞

      Volume: 50 Pages: 323-326

    • Related Report
      2018 Annual Research Report
  • [Journal Article] 中枢神経回路の可塑的再構築2018

    • Author(s)
      植田禎史
    • Journal Title

      アグリバイオ

      Volume: 2 Pages: 1118-1121

    • NAID

      40021807756

    • Related Report
      2018 Annual Research Report
  • [Journal Article] 神経損傷に伴う体部位再現図の再構築2018

    • Author(s)
      植田禎史
    • Journal Title

      Precision Medicine

      Volume: 1 Pages: 259-299

    • Related Report
      2018 Annual Research Report
  • [Presentation] Regulation of aberrant synaptic remodeling in the thalamus triggered by peripheral nerve injury.2019

    • Author(s)
      Yoshifumi Ueta, Mariko Miyata
    • Organizer
      The 9th FAOPS Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Suppression of microglia prevents nerve injury-induced synapse remodeling in the thalamus.2018

    • Author(s)
      Yoshifumi Ueta, Mariko Miyata
    • Organizer
      Cold Spring Harbor Asia "Latest Advances in Development & Function of Neuronal Circuits"
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Suppression of microglia prevents nerve injury-induced remodeling of thalamic circuits and ectopic allodynia.2018

    • Author(s)
      Yoshifumi Ueta, Sachie Sekino, Yuichi Takeuchi, Yoko Katayama, Mariko Miyata.
    • Organizer
      第41回 日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 神経損傷に伴う体性感覚視床のシナプス改編におけるミクログリアの役割2018

    • Author(s)
      植田禎史, 関野紗知絵, 片山洋子, 宮田麻理子
    • Organizer
      新学術領域研究「グリアアセンブリによる脳機能発現の制御と病態」第5回班会議
    • Related Report
      2017 Research-status Report
  • [Presentation] Developmental and nerve-injury induced regulation of microglia function in mouse somatosensory circuits.2018

    • Author(s)
      Yoshifumi Ueta, Sachie Sekino, Futaba Miyoshi, Yuki Yagasaki, Yoko Katayama, Mariko Miyata
    • Organizer
      Glial assembly: a new regulatory machinery of brain function and disorders
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 発達期および神経損傷によって生じる体性感覚経路のシナプス改編におけるミクログリア活性の役割2017

    • Author(s)
      宮田麻理子, 植田禎史, 矢ヶ崎有希, 片山洋子, 尾崎弘展
    • Organizer
      新学術領域研究「グリアアセンブリによる脳機能発現の制御と病態」第4回成果報告会
    • Place of Presentation
      九州大学医学部 百年講堂(福岡県福岡市)
    • Year and Date
      2017-01-06
    • Related Report
      2016 Research-status Report
  • [Presentation] マウスのヒゲ感覚経路における発達期および神経損傷によるミクログリア制御2017

    • Author(s)
      植田禎史, 矢ヶ崎有希, 片山洋子, 尾崎弘展, 宮田麻理子
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Microglial function is regulated by development and peripheral nerve injury in the whisker-related somatosensory pathway.2017

    • Author(s)
      植田禎史, 矢ヶ崎有希,三好ふたば,片山洋子, 尾崎弘展, 宮田麻理子
    • Organizer
      新学術領域研究「グリアアセンブリによる脳機能発現の制御と病態」第4回夏のワークショップ
    • Related Report
      2017 Research-status Report
  • [Presentation] Role of microglial function in neural remodeling of somatosensory circuits following peripheral nerve injury2016

    • Author(s)
      植田禎史, 尾崎弘展, 矢ヶ崎有希, 片山洋子, 宮田麻理子
    • Organizer
      新学術領域研究「グリアアセンブリによる脳機能発現の制御と病態」 第3回夏のワークショップ
    • Place of Presentation
      山形国際ホテル(山形県山形市)
    • Year and Date
      2016-07-15
    • Related Report
      2016 Research-status Report

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

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