Role of microglia polarization induced by glucose metabolism disorder in the cognitive impairment of mice from PM 2.5 exposure.

Studies have found that PM _2.5 can damage the brain, accelerate cognitive impairment, and increase the risk of developing a variety of neurodegenerative diseases. However, the potential molecular mechanisms by which PM _2.5 causes learning and memory problems are yet to be explored. In this study, we evaluated the neurotoxic effects in mice after 12 weeks of PM _2.5 exposure, and found that this exposure resulted in learning and memory disorders, pathological brain damage, and M1 phenotype polarization on microglia, especially in the hippocampus. The severity of this damage increased with increasing PM _2.5 concentration. Proteomic analysis, as well as validation results, suggested that PM _2.5 exposure led to abnormal glucose metabolism in the mouse brain, which is mainly characterized by significant expression of hexokinase, phosphofructokinase, and lactate dehydrogenase. We therefore administered the glycolysis inhibitor 2-deoxy-d-glucose (2-DG) to the mice exposed to PM _2.5 , and showed that inhibition of glycolysis by 2-DG significantly alleviated PM _2.5 -induced hippocampal microglia M1 phenotype polarization, and reduced the release of inflammatory factors, improved synaptic structure and related protein expression, which alleviated the cognitive impairment induced by PM _2.5 exposure. In summary, our study found that abnormal glucose metabolism-mediated inflammatory polarization of microglia played a role in learning and memory disorders in mice exposed to PM _2.5 . This study provides new insights into the neurotoxicity caused by PM _2.5 exposure, and provides some theoretical references for the prevention and control of cognitive impairment induced by PM _2.5 exposure.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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