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Mechanism of brain function and pathogenesis induced by glial cell-mediated synaptic refinement

Research Project

Project/Area Number 18K06457
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 46010:Neuroscience-general-related
Research InstitutionTohoku University

Principal Investigator

Morizawa Yosuke  東北大学, 生命科学研究科, JSPS特別研究員(PD) (50772167)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords貪食 / グリア / アストロサイト / ミクログリア / 神経回路再編 / シナプスリモデリング / シナプス除去 / プローブ / シナプス再編 / 神経障害性疼痛 / 運動学習
Outline of Final Research Achievements

Neural circuits (synapses) remodeling is the fundamental process of learning and memory in the normal brain. In pathological conditions, it could promote the formation of inappropriate neural circuits and cause pathological deficits. In this study, we aimed to elucidate the mechanism of synapse loss.
One possible mechanism is removal of synapses by surrounding glia through phagocytosis. However, the phagocytosed materials are rapidly digested, making them difficult to detect. To solve this problem, we generated new transgenic mice line that express fluorescent probes, which are relatively resistant to mammalian lysosomes, in a cell type- and timing-specific manner. By expressing these probes on target neurons, we established a new tool that can qualitatively and quantitatively evaluate the phagocytosis of surrounding glial cells during development, learning, and brain injury.

Academic Significance and Societal Importance of the Research Achievements

貪食を可視化する新規遺伝子改変マウスの作出およびその有用性について詳細に解析・評価を行い、従来、貪食性細胞として注目されていなかった細胞による神経回路再編が、発達後の脳内でも盛んに生じていることを明らかにした。コミュニティ内で渇望されてきた新ツールの開発・提供により、他疾患モデル等におけるシナプス貪食の探索型の研究が可能となるだけでなく、神経回路再編以外にも様々な貪食研究に応用可能な有益なツールと考えられる。

Report

(2 results)
  • 2020 Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2019 2018

All Presentation (3 results) (of which Int'l Joint Research: 2 results)

  • [Presentation] Role of glial phagocytosis of synapses in physiological memory engravement process2019

    • Author(s)
      Yosuke Morizawa and Ko Matsui
    • Organizer
      Glial Biology, Gordon Research Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Purinergic regulation of astrocytic phagocytosis2018

    • Author(s)
      Yosuke Morizawa and Schuichi Koizumi
    • Organizer
      Glia in Health & Disease, Cold Spring Harbor Laboratory Meeting(
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Brain Remodeling by Astrocytic Phagocytosis2018

    • Author(s)
      Yosuke Morizawa, Schuichi Koizumi, Ko Matsui
    • Organizer
      The Joint Congress of The 40th Annual Meeting of JSBP and The 61st Annual Meeting of JSN
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-12-25  

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