| Project/Area Number |
17K19457
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neuroscience and related fields
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 薬理学 / 神経科学 / ストレス / ミクログリア / エピゲノム制御 / 転写因子 |
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| Outline of Final Research Achievements |
Social stress often induces emotional alterations such as depression, and can be a risk factor for mental illness. However, the mechanism remains elusive. Using a mouse model of social defeat stress, here we found that repeated stress exposure activates prefrontal microglia through innate immune receptors TLR2/4 and consequently leads to dendritic atrophy of prefrontal neurons and depression-like behavior. We also identified transcription factors whose expression was altered similarly in TLR2/4-stimulated cultured microglia and repeated stress-activated prefrontal microglia, and analyzed their functions in cultured microglia.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果は、ストレスによる情動変容にミクログリア活性化を中心とする脳内炎症反応が重要であることを世界に先駆けて立証し、ストレスによるミクログリア活性化・プライミングに関わる転写因子群の抽出にも成功した。さらにストレスによる脳内炎症のエピゲノム制御を網羅的に解析するための技術基盤を確立した。これらの成果はストレスによる脳機能変化の不可逆性の生物学的基盤に迫る点で学術的意義は大きく、また精神疾患創薬のための新たな標的を提示する点で社会的意義も大きい。
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