TREM2 deficiency mitigates neuroinflammation and hippocampal damage induced by subchronic 1-bromopropane exposure in...

1-Bromopropane (1-BP), a widely used industrial solvent, has been increasingly recognized for its neurotoxic potential. Neuroinflammation has emerged as a key pathological mechanism underlying 1-BP-induced neuronal injury and cognitive impairment. Triggering receptor expressed on myeloid cells 2 (TREM2) has been implicated in various neurodegenerative and toxicant-induced neurological conditions. However, the specific contribution of TREM2 to 1-BP-induced neurotoxicity remains inadequately defined. This study aimed to elucidate the role of TREM2 in mediating neuroinflammatory responses and neuronal damage following 1-BP exposure, with a focus on its involvement in hippocampal neurodegeneration and cognitive deficits. In this investigation, a murine model of subchronic 1-BP exposure was established, and TREM2 gene knockout strategies were employed to assess its impact on microglial activation, inflammatory signaling cascades, and neuronal integrity. Behavioral assessments, immunohistochemistry, and molecular analyses were conducted to evaluate cognitive function, neuroinflammation, and cell death pathways. The results demonstrated that 1-BP exposure significantly activated microglia and upregulated the expression of both TREM2 and key components of the NOD-like receptor family pyrin domain containing 3(NLRP3) inflammasome within the hippocampus. In contrast, TREM2 deficiency markedly alleviated 1-BP-induced impairments in learning and memory, suppressed the expression of pro-inflammatory cytokines, and reduced hippocampal neuronal loss. Furthermore, knockout of TREM2 resulted in a significant decrease in the number of dying neurons, accompanied by downregulation of necroptosis-associated proteins. Collectively, these findings suggest that TREM2 plays a key role in 1-BP-related neuroinflammation and neuron damage. Targeting TREM2 could be a promising therapeutic strategy to mitigate the adverse neurological consequences of 1-BP exposure.