TMEM119-defined brain macrophage phenotypes in a chronic stress model induced by corticosterone in male mice

Microglia are crucial for brain immunity, and their phenotypic changes have been implicated in neuroinflammation and the development of depression and anxiety symptoms. The accurate characterization of these changes is challenging due to the interaction of microglia with the brain microenvironment and the presence of central nervous system (CNS)-resident macrophages that share common markers with microglia. Using the microglia-specific marker TMEM119 and bone marrow chimeric mice, we investigated the changes in microglial activity in mice exposed to chronic corticosterone, a widely used rodent model of stress-related behaviors. Flow cytometry analysis was used to identify TMEM119^{intermidiary (int)}, CD45^low microglia and TMEM119^{high (hi)}, CD45^int microglia. Notably, corticosterone exposure led to a significant increase in the number of TMEM119^int, CD45^low microglia, whereas the proportions of TMEM119^hi, CD45^int microglia remained unchanged. The increased forward and side scatter properties of TMEM119^hi, CD45^int microglia suggest increased intracellular granularity, which may reflect distinct phenotypic features of this previously overlooked cell population. Our finding of an increased population of TMEM119^hi, CD45^int microglia may reflect a stress-adapted phenotype similar to that of clinical depression.