Stress-induced disturbances of brain homeostasis and neuroinflammation have been implicated in the pathophysiology of mood disorders. In major depressive disorder (MDD), elevated levels of proinflammatory cytokines and chemokines can be found in peripheral blood, but very little is known about the changes that occur directly in the brain. Microglia are the primary immune effector cells of the central nervous system and exquisitely sensitive to changes in the brain microenvironment. Here, we performed the first single-cell analysis of microglia from four different post-mortem brain regions (frontal lobe, temporal lobe, thalamus, and subventricular zone) of medicated individuals with MDD compared to controls. We found no evidence for the induction of inflammation-associated molecules, such as CD11b, CD45, CCL2, IL-1β, IL-6, TNF, MIP-1β (CCL4), IL-10, and even decreased expression of HLA-DR and CD68 in microglia from MDD cases. In contrast, we detected increased levels of the homeostatic proteins P2Y₁₂ receptor, TMEM119 and CCR5 (CD195) in microglia from all brain regions of individuals with MDD. We also identified enrichment of non-inflammatory CD206^hi macrophages in the brains of MDD cases. In sum, our results suggest enhanced homeostatic functions of microglia in MDD.

压力引起的脑稳态紊乱和神经炎症与情绪障碍的病理生理学有关。在重度抑郁症 (MDD) 中，外周血中可发现促炎细胞因子和趋化因子水平升高，但对直接发生在大脑中的变化知之甚少。小胶质细胞是中枢神经系统的主要免疫效应细胞，对大脑微环境的变化非常敏感。在这里，我们对 MDD 患者与对照组的四个不同死后大脑区域（额叶、颞叶、丘脑和脑室下区）的小胶质细胞进行了第一次单细胞分析。我们没有发现诱导炎症相关分子的证据，例如 CD11b、CD45、CCL2、IL-1β、IL-6、TNF、MIP-1β (CCL4)、IL-10、甚至降低 MDD 病例小胶质细胞中 HLA-DR 和 CD68 的表达。相比之下，我们检测到稳态蛋白质 P2Y 的水平增加₁₂受体、TMEM119 和 CCR5 (CD195) 在来自 MDD 患者所有大脑区域的小胶质细胞中。我们还确定了 MDD 病例大脑中非炎症性 CD206 ^hi巨噬细胞的富集。总之，我们的结果表明 MDD 中小胶质细胞的稳态功能增强。