Elucidation of mechanisms for regulating microglial activation underlying brain microenvironmental deterioration

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16372
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Kobe University
• Principal Investigator: Masayuki Taniguchi 神戸大学, 医学研究科, 特命助教 (90831751)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: ミクログリア / ストレス / 脳内炎症 / エピゲノム

Outline of Final Research Achievements

Social stress often induces emotional alterations such as depression and anxiety, and can be a risk factor for mental illness. However, the mechanism remains unknown. Recently studies suggest that chronic stress induces neuroinflammation through microglia activation. Using a mouse model of social defeat stress, here we found that repetition of stress exposure induces brain region-specific epigenomic changes in microglia and these epigenetic changes are concordant with the expression of adjacent genes associated with different biological functions. Furthermore, we specified transcription factors associated with epigenomic changes. These results suggest that stress induces epigenomic changes in microglia, which may contribute to neuroinflammation for emotional disturbances.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

ミクログリア活性化は情動変容に関わる脳内炎症に重要である。本研究の成果は、ストレスによるミクログリア活性化・プライミングにはエピゲノム変化が重要であることを示し、その変化に関わる転写因子群の抽出に成功した。これらの成果はストレスによる脳機能変化の難可逆性の生物学的基盤に迫る点で学術的意義は大きく、またストレス関連疾患の病態の解明や、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。