Snijders Gijsje J L J, Sneeboer Marjolein A M, Fernández-Andreu Alba, Udine Evan, Boks Marco P, Ormel Paul R, van Berlekom Amber Berdenis, van Mierlo Hans C, Bӧttcher Chotima, Priller Josef, Raj Towfique, Hol Elly M, Kahn René S, de Witte Lot D
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, 3584, CG, Utrecht, The Netherlands.
Mol Psychiatry. 2021 Jul;26(7):3336-3349. doi: 10.1038/s41380-020-00896-z. Epub 2020 Oct 7.
Findings from epidemiological studies, biomarker measurements and animal experiments suggest a role for aberrant immune processes in the pathogenesis of major depressive disorder (MDD). Microglia, the resident immune cells of the brain, are likely to play a key role in these processes. Previous post-mortem studies reported conflicting findings regarding microglial activation and an in-depth profiling of those cells in MDD is lacking. The aim of this study was therefore to characterize the phenotype and function of microglia in MDD. We isolated microglia from post-mortem brain tissue of patients with MDD (n = 13-19) and control donors (n = 12-25). Using flow cytometry and quantitative Polymerase Chain Reaction (qPCR), we measured protein and mRNA levels of a panel of microglial markers across four different brain regions (medial frontal gyrus, superior temporal gyrus, thalamus, and subventricular zone). In MDD cases, we found a significant upregulation of CX3CR1 and TMEM119 mRNA expression and a downregulation of CD163 mRNA expression and CD14 protein expression across the four brain regions. Expression levels of microglial activation markers, such as HLA-DRA, IL6, and IL1β, as well as the inflammatory responses to lipopolysaccharide and dexamethasone were unchanged. Our findings suggest that microglia enhance homeostatic functions in MDD but are not immune activated.
流行病学研究、生物标志物测量和动物实验的结果表明，异常免疫过程在重度抑郁症（MDD）的发病机制中起作用。小胶质细胞作为大脑中的常驻免疫细胞，可能在这些过程中发挥关键作用。先前的尸检研究报告了关于小胶质细胞激活的相互矛盾的结果，并且缺乏对MDD中这些细胞的深入分析。因此，本研究的目的是表征MDD中小胶质细胞的表型和功能。我们从MDD患者（n = 13 - 19）和对照供体（n = 12 - 25）的死后脑组织中分离出小胶质细胞。使用流式细胞术和定量聚合酶链反应（qPCR），我们测量了四个不同脑区（内侧前额叶皮层、颞上回、丘脑和脑室下区）中小胶质细胞标志物的蛋白质和mRNA水平。在MDD病例中，我们发现四个脑区中CX3CR1和TMEM119 mRNA表达显著上调，CD163 mRNA表达和CD14蛋白表达下调。小胶质细胞激活标志物如HLA - DRA、IL6和IL1β的表达水平以及对脂多糖和地塞米松的炎症反应没有变化。我们的研究结果表明，小胶质细胞增强了MDD中的稳态功能，但未被免疫激活。
