Yoblinski Andrew R, Dubey Jyoti, Myers Tyler, Sathees Nitya, Volk David W, Fish Kenneth N, Seney Marianne L
Department of Psychiatry and Translational Neuroscience Program, University of Pittsburgh Medical School, 450 Technology Drive Suite 223, Pittsburgh, PA 15213, United States.
VISN 4 Mental Illness Research Education and Clinical Center (MIRECC), VA Pittsburgh Healthcare System, University Drive C, Pittsburgh, PA 15240, United States.
Cereb Cortex. 2025 May 1;35(5). doi: 10.1093/cercor/bhaf120.
Microglia exhibit complex and dynamic morphology that is linked to function. Altered microglia function has been implicated in multiple diseases of the brain, including elevated phagocytosis of neuronal dendritic spines in schizophrenia. However, understanding the relationship between altered microglia and pathophysiology first requires a clearer picture of microglia morphology in the non-diseased brain, which has yet to be fully established. Here, we deploy immunostaining and confocal microscopy to sample over 1,300 microglia from two prefrontal cortex (PFC) subregions in postmortem human brain (3 males, 3 females). We use Neurolucida 360 to trace the 3-dimensional structure of these microglia and quantify interactions with dendritic spines. We find that PFC microglia in male subjects display overall more complex branching than in female subjects, and subgenual anterior cingulate cortex (sgACC) microglia are more complexly branched with more round somas than those in the dorsolateral PFC (DLPFC), irrespective of sex. Furthermore, a lower proportion of phagocytic burden in sgACC microglia involves engulfment of dendritic spines compared to DLPFC. Overall, our results paint a detailed and nuanced picture of microglia morphology and function in subjects unaffected by psychiatric or neurologic illness that can be used as a benchmark for future studies of the diseased brain.
小胶质细胞呈现出与功能相关的复杂动态形态。小胶质细胞功能改变与多种脑部疾病有关，包括精神分裂症中神经元树突棘吞噬作用增强。然而，要理解小胶质细胞改变与病理生理学之间的关系，首先需要更清楚地了解未患病大脑中小胶质细胞的形态，而这一点尚未完全明确。在这里，我们采用免疫染色和共聚焦显微镜技术，从死后人类大脑的两个前额叶皮质（PFC）亚区域采集了1300多个小胶质细胞样本（3名男性，3名女性）。我们使用Neurolucida 360追踪这些小胶质细胞的三维结构，并量化它们与树突棘的相互作用。我们发现，男性受试者的PFC小胶质细胞总体上比女性受试者的分支更复杂，并且无论性别如何，膝下前扣带回皮质（sgACC）的小胶质细胞比背外侧PFC（DLPFC）的小胶质细胞分支更复杂，胞体更圆。此外，与DLPFC相比，sgACC小胶质细胞中吞噬负担涉及吞噬树突棘的比例更低。总体而言，我们的结果描绘了未受精神或神经疾病影响的受试者中小胶质细胞形态和功能的详细而细微的图景，可作为未来患病大脑研究的基准。
