TREM2 mitigates NLRP3-mediated neuroinflammation through the NF-κB and PI3k/Akt signaling pathways in juvenile rats exposed to ambient particulate matter

Ambient particulate matter (PM) is a global public and environmental problem. PM is closely associated with several neurological disorders that typically involve neuroinflammation. There have been few studies on the effect of PM on neuroinflammation to date. In this study, we used a juvenile rat model (PM exposure was conducted at a dose of 10 mg/kg body weight per day for 4 weeks) and a BV-2 cell model (PM exposure was conducted at concentrations of 50, 100, 150, and 200 μg/ml for 24 h) to investigate PM-induced neuroinflammation mediated by NLRP3 inflammasome activation and the role of TREM2 in this process. Our findings revealed that PM exposure reduced TREM2 protein and mRNA levels in the rat hippocampus and BV-2 cells. TREM2 overexpression attenuated PM-induced spatial learning and memory deficits in rats. Moreover, we observed that TREM2 overexpression in vivo and in vitro effectively mitigated the increase in NLRP3 and pro-Caspase1 protein expression, as well as the secretion of IL-1β and IL-18. Exposure to PM increased the expression of NF-κB and decreased the phosphorylation of PI3k/Akt in vivo and in vitro, and this process was effectively reversed by overexpressing TREM2. Our results indicated that PM exposure could reduce TREM2 expression and induce NLRP3 inflammasome-mediated neuroinflammation and that TREM2 could mitigate NLRP3 inflammasome-mediated neuroinflammation by regulating the NF-κB and PI3k/Akt signaling pathways. These findings shed light on PM-induced neuroinflammation mechanisms and potential intervention targets.