期刊
BIOENGINEERED
卷 13, 期 1, 页码 521-530出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/21655979.2021.2009971
关键词
Mirtazapine; isoflurane; cognitive dysfunction; microglia activation; neuroinflammation; oxidative stress
资金
- Cangzhou Central Hospital
The study demonstrates that mirtazapine has a protective effect on BV2 microglia against activation, neuroinflammation, and oxidative stress caused by isoflurane exposure. This effect may be mediated by the activation of TREM2. Therefore, mirtazapine could be a potential intervention strategy to prevent isoflurane exposure-induced cognitive dysfunction.
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)-1 beta 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.
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