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社交隔离会导致小胶质细胞状态出现性别和脑区特异性改变。

Social isolation produces a sex- and brain region-specific alteration of microglia state.

机构信息

Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.

Department of Medicine, Division of Neurology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.

出版信息

Eur J Neurosci. 2023 May;57(9):1481-1497. doi: 10.1111/ejn.15966. Epub 2023 Mar 23.

DOI:10.1111/ejn.15966
PMID:36918398
Abstract

Social isolation is a profound form of psychological stress that impacts the mental health of a large proportion of society. Other experimental models of stress have demonstrated a microglia response that serves either a protective or pathological function. However, the effect of adult social isolation on microglia has not been thoroughly investigated. We measured microglia territory, branching, end points and phagocytic-lysosomal activity in group housed C57Bl/6 mice and mice that were socially isolated for 2 weeks. Our results show that the dorsomedial hypothalamus and hippocampal CA2 region of adult male mice undergo increased microglia volume, territory and endpoints following social isolation, whereas females exhibit this increase in the hypothalamus only. Males exhibited decreases in the phagocytic-lysosomal marker CD68 in microglia in these regions, whereas females showed an increase in CD68 in the hypothalamus suggesting sexually dimorphic and brain region-specific change in microglia state in response to social isolation. The prefrontal cortex, central amygdala, nucleus accumbens shell and visual cortex did not exhibit changes in microglia structure in either male or female mice. These data show that microglia in different brain regions undergo a distinct response to social isolation which may account for changes in cognition and behaviour associated with this prevalent form of psychological stress.

摘要

社会隔离是一种深刻的心理压力形式,影响着很大一部分社会的心理健康。其他应激的实验模型表明小胶质细胞反应具有保护或病理功能。然而,成年社会隔离对小胶质细胞的影响尚未得到彻底研究。我们测量了群居 C57Bl/6 小鼠和社交隔离 2 周的小鼠的小胶质细胞领地、分支、末端和吞噬溶酶体活性。我们的结果表明,成年雄性小鼠的背内侧下丘脑和海马 CA2 区在社会隔离后经历了小胶质细胞体积、领地和末端的增加,而雌性只在下丘脑表现出这种增加。雄性在这些区域的小胶质细胞中吞噬溶酶体标记物 CD68 减少,而雌性在下丘脑 CD68 增加,表明小胶质细胞状态对社会隔离的反应存在性别二态性和脑区特异性变化。前额叶皮层、中央杏仁核、伏隔核壳和视皮层在雄性或雌性小鼠中均未表现出小胶质细胞结构的变化。这些数据表明,不同脑区的小胶质细胞对社会隔离有不同的反应,这可能解释了与这种普遍心理压力相关的认知和行为变化。

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