Inflammatory Signatures of Microglia in the Mouse Model of Corticosterone-Induced Depression

Microglia-mediated inflammation has been recognized as a key feature of major depressive disorder. Although hypercortisolemia is commonly observed in depressed patients and can be predictive of treatment response, how such chronic exposure to this stress hormone may influence microglia is incompletely characterized. Here, we exploited a standard mouse model of depressive-like behaviors induced by repeated peripheral administration of corticosterone. Microglia in the prefrontal cortex of mice were profiled by bulk RNA sequencing, which exhibited increased expression of inflammatory markers. In addition, single-cell RNA sequencing further identified distinct molecular patterns of microglial responses. Moreover, we revealed the up-regulation of Pu.1 and Irf8, the two central transcription factors governing microglia-mediated inflammation, in the prefrontal cortex and hippocampus of corticosterone-treated mice, which similarly occurred in depressed patients' microglia. These results have established the inflammatory signatures of microglia in the mouse model recapitulating hypercortisolemia-related depression, providing new insights into developing diagnostic and therapeutic strategies. The C57BL/6 mice were treated with corticosterone by oral gavage for the model of hypercotisolemia-related depression. Then the microglia were sorted as CD45low CD11b+ by the common standard from the prefrontal cortex of vehicle- or corticosterone-treated mice and analyzed using scRNA-seq.