| Project/Area Number |
18K15003
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 48010:Anatomy-related
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| Research Institution | Nagoya University |
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Principal Investigator |
Hattori Yuki 名古屋大学, 医学系研究科, 特任助教 (10754955)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | ミクログリア / ニューロン / 脳発生 / ライブイメージング / CXCL12 / CXCR4 / 大脳 / 神経前駆細胞 / 二光子顕微鏡 / スライス培養 / 細胞移動 / CX3CR1 / 分布変化 / CXCL12/CXCR4 |
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| Outline of Final Research Achievements |
Microglia change their distribution in a stage-dependent manner in the embryonic cerebral cortex. In mice, intrapallial microglial distribution is initially homogenous until embryonic day (E) 14, but these cells temporarily disappear from the cortical plate (CP) from E15 to E16. However, the mechanism and significance of this absence are unknown. We demonstrated that microglia bidirectionally migrate via attraction by CXCL12 released from the meninges and SVZ, and thereby exit the midembryonic CP. In addition, postmigratory neurons exposed to excessive microglia showed the disturbed expression pattern of genes implicated in functional neuronal maturation. Notably, this effect is primarily attributed to interleukin 6 and type I interferon secreted by microglia. These results suggest that "sanctuarization" from microglia in the midembryonic CP is required for neurons to appropriately fine-tune the expression of molecules needed for proper differentiation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、正常脳におけるミクログリアの動態や神経系細胞との関わり合いについて理解が深まった。胎生期のみならず生後にわたる脳形成・成熟メカニズムの包括的な理解に貢献すると考えられる。一方で、母体の過剰な免疫活性化（感染症、肥満・低栄養状態）が、胎児の統合失調症、自閉症、ADHD等の発症リスクを高めることが報告されており、近年社会的にも母体炎症による胎児脳発生への影響について関心が高まっている。そこで発展的展望として、母体炎症に起因する脳発生の異常を未然に防ぐための予防法や治療法の画策など社会的ニーズに応じた研究展開も考えていきたい。
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