Dexamethasone Induces a Specific Form of Ramified Dysfunctional Microglia

초록

The functional status of dynamic microglial cells plays an important role in maintaining homeostasis of microenvironment in CNS. In a previous study, we reported that microglia phenotype might be involved in stress vulnerability and depression recurrence. Here, we aimed to clarify a character of microglia exposed persistently to glucocorticoid (GC), which is representative a stress hormone, in primary cultured microglial cells. Five nanomolars of dexamethasone (DEX, GC agonist) for 72h decreased CX3CR1 and CD200R expression and induced ramified form of microglial cells in similar morphology to in vivo resident microglia. However, the ramified form of microglia did not increase microglia signature genes such as P2RY12, OLFML3, TMEM119, and TGFBR1. In addition, DEX-treated microglia showed a reduction of phagocytosis function, pro-and anti-inflammatory cytokine production, and cell proliferation. DEX washout did not restore these changes. Based on transcriptomic analysis and functional characters of DEX-treated microglia, we performed senescence-associated beta-galactosidase (SA- gal) assay in DEX-treated microglia and DEX-treated microglia showed more SA- gal activity with alteration of cell cycle-related genes. Thus, our results suggest that DEX can induce a specific phenotype of microglia (like-senescence).

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