マウスの慢性社会ストレスによるミクログリアの遺伝子発現状態遷移

• Published in: 日本薬理学会年会要旨集 p. 3-B-SS14-1
• Main Authors: 谷口, 将之, 松下, 和敏, 古屋敷, 智之, 三島, 零
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: forebrain; gene expression; microglia; stress
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.96.0_3-B-SS14-1

Microglia-derived neuroinflammation has been associated with the stress pathology of mental illness. However, the nature of microglial stress responses remains poorly understood. Using single-cell transcriptome analyses, we found that acute and chronic social defeat stress altered the transcriptome of microglia in multiple brain areas, including the medial prefrontal cortex (mPFC), primary motor and sensory cortices, hippocampus, nucleus accumbens, and hypothalamus, in mice. Despite some brain region-specific patterns, individual variability of stress-susceptibility emerged broadly across the brain areas. We further analyzed transcriptomes of mPFC microglia, the activation of which are essential for chronic stress-induced depression-like behavior, and identified several transcriptomic states of microglia, through which chronic stress promoted the transition from a homeostatic state to a distinct state with brain region-specificity and stress susceptibility signature. These findings demonstrate multiple states of microglia reflecting brain area specification and stress susceptibility, the transition of which may contribute to the stress pathology of mental illness.