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Elucidation of the significance of the novel structure BUDO in the developing brain

Research Project

Project/Area Number 20K21457
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 46:Neuroscience and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Koyama Ryuta  東京大学, 大学院薬学系研究科(薬学部), 准教授 (90431890)

Project Period (FY) 2020-07-30 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsミクログリア / 貪食 / 血管 / 赤血球 / マイクログリア / マクロファージ / 発達期
Outline of Research at the Start

本研究では、発達期マウス脳内で新規に発見した構造物BUbbly Dense Organization (BUDO)の細胞種を詳細に同定し、その機能や存在意義を探索することを目的とした研究を行う。特に、BUDOの細胞種と機能、そして機能制御の方法の確立を目指し、脳発達における脳内免疫システムを制御する新たな細胞生物学的メカニズムを解明する。

Outline of Final Research Achievements

When a significant amount of bleeding occurs in the brain, it leads to the release of cytotoxic components from the blood, resulting in brain tissue damage and subsequent dysfunction. In this study, we aimed to investigate the cellular response to intracerebral hemorrhage and elucidate its underlying mechanism in early postnatal mice. Our results showed that intracerebral hemorrhage in mice occurs extensively throughout the brain at approximately two weeks after birth. Furthermore, we observed that microglia phagocytose erythrocytes and adopt a BUDO (BUbbly Dense Organization) structure at the site of hemorrhage. Notably, we found that erythrophagocytic microglia play a cytoprotective role through the expression of heme oxygenase-degrading enzyme (HO-1) and display a distinct gene expression pattern compared to non-phagocytic microglia.

Academic Significance and Societal Importance of the Research Achievements

本研究では、健常マウスにおいて生後初期限定的に脳内出血が生じていることを発見した。そして、マイクログリアが葡萄の様な構造をとり(BUDO構造)、HO-1を介して赤血球を貪食することで、発達期脳における細胞保護的な役割を担うことを明らかにした。さらに、赤血球除去がほぼ終了している生後2週齢においては、HO-1発現マイクログリアは成熟マイクログリアの形態を示す一方で、マイクログリア恒常性遺伝子の発現低下をはじめ特徴的な遺伝子発現を示すことを明らかにした。本研究は、脳内出血を生後初期マウスで初めて網羅的に解析し、それに対するマイクログリアの細胞応答や分子メカニズムを明らかにした点で意義深いと考える。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (8 results)

All 2022 2021

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (3 results)

  • [Journal Article] Thermosensitive receptors in neural stem cells link stress-induced hyperthermia to impaired neurogenesis via microglial engulfment2021

    • Author(s)
      Hoshi Yutaka、Shibasaki Koji、Gailly Philippe、Ikegaya Yuji、Koyama Ryuta
    • Journal Title

      Science Advances

      Volume: 7 Issue: 48

    • DOI

      10.1126/sciadv.abj8080

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparative Review of Microglia and Monocytes in CNS Phagocytosis2021

    • Author(s)
      Andoh Megumi、Koyama Ryuta
    • Journal Title

      Cells

      Volume: 10 Issue: 10 Pages: 2555-2555

    • DOI

      10.3390/cells10102555

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extracellular Vesicles Taken up by Astrocytes2021

    • Author(s)
      Ogaki Ari、Ikegaya Yuji、Koyama Ryuta
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 19 Pages: 10553-10553

    • DOI

      10.3390/ijms221910553

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phagocytic Glial Cells in Brain Homeostasis2021

    • Author(s)
      Kono Rena、Ikegaya Yuji、Koyama Ryuta
    • Journal Title

      Cells

      Volume: 10 Issue: 6 Pages: 1348-1348

    • DOI

      10.3390/cells10061348

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microglia regulate synaptic development and plasticity2021

    • Author(s)
      Andoh M, Koyama R.
    • Journal Title

      Developmental Neurobiology

      Volume: - Issue: 5 Pages: 568-590

    • DOI

      10.1002/dneu.22814

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 小児期の赤血球貪食によるマイクログリアのヘテロ性の創出2022

    • Author(s)
      小山隆太
    • Organizer
      第95回 日本生化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 貪食に伴って変化するミクログリア情報のデコーディング2022

    • Author(s)
      小山隆太
    • Organizer
      第95回日本薬理学会
    • Related Report
      2022 Annual Research Report 2021 Research-status Report
  • [Presentation] The role of erythrophagocytosis by microglia in brain development2022

    • Author(s)
      小山隆太
    • Organizer
      第44回日本分子生物学会
    • Related Report
      2021 Research-status Report

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Published: 2020-08-03   Modified: 2024-01-30  

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