Elucidation of machinery for brain homeostasis and its disruption associated with emotional abnormalities by microglia

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15268
• 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: Taniguchi Masayuki 神戸大学, 医学研究科, 特命助教 (90831751)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: ストレス / ミクログリア / エピゲノム

Outline of Final Research Achievements

Social stress often induces cognitive emotional abnormalities such as depression and anxiety, and can be a risk factor for mental illness. Our studies suggest that chronic stress induces neuroinflammation through microglia activation. However, the nature of microglial activation and its mechanism remain unknown. Here we developed a technique to analyze microglial diversity across the brain regions. Using epigenetic and transcriptome analyses, we found several signaling pathways involved in microglial activation and their gene expression responses. We also found that these pathways contribute to stress-induced emotional abnormalities. These findings suggest that microglia integrate several stress-induced signaling pathways and promote emotional abnormalities.

Free Research Field

神経科学

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、ミクログリアはストレスによる複数の情報伝達経路を統合し、情動変容に関わることを示した。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い。また、治療抵抗性の精神疾患において新規治療標的の探索が不可欠であり、本研究成果はストレス関連疾患の病態の解明のみならず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。