Abstract
Mirtazapine is an antidepressant drug that has been proven to possess a cognitive enhancer efficiency. In this study, we evaluated the potential protective effects of mirtazapine on BV2 microglia in response to isoflurane exposure. Our results show that mirtazapine attenuated isoflurane-induced expression of microglia-specific protein Iba1 in BV2 microglia. Mirtazapine prevented isoflurane-induced production of the pro-inflammatory factors interleukin (IL)-1β and IL-18 by inhibiting the activation of the nod-like receptor family protein 3 (NLRP3) inflammasome in BV2 microglia. The increased reactive oxygen species (ROS) production and elevated expression level of NADPH oxidase 4 (NOX4) in isoflurane-induced BV2 microglia were mitigated by mirtazapine. Isoflurane exposure reduced triggering receptor expressed on myeloid cells 2 (TREM2) expression in BV2 microglia, which was restored by mirtazapine. Moreover, silencing of TREM2 abolished the inhibitory effects of mirtazapine on ionized calcium-binding adapter molecule 1 (Iba1) expression and inflammation in BV2 microglia. From these results, we could infer that mirtazapine exerted a protective effect on BV2 microglia against isoflurane exposure-caused microglia activation, neuroinflammation, and oxidative stress via inducing TREM2 activation. Hence, mirtazapine might be a potential intervention strategy to prevent isoflurane exposure-caused cognitive dysfunction in clinical practice.