Ambient PM-induced brain injury is associated with the activation of PI3K/AKT/FoxO1 pathway.

PM-related neurological and mental diseases, such as cognitive impairment and stroke, tend to cause disability. Six-week-old male C57BL/6 mice were divided into 6 groups and exposed to concentrated PM or filtered air for 2, 4, and 6 months, respectively. The neurobehavioral changes of mice were tested. The weight of the whole brain and olfactory bulbs were recorded at the end of exposure, and the brain structure was observed by hematoxylin and eosin (HE) staining. Serum indicators, mRNA, and protein expressions were detected. The spatial learning memory ability was impaired, and the mice were more anxious after PM exposure. Relative brain weight decreased with age, and PM exposure exceeded the decrease of relative brain weight. Interestingly, superoxide dismutase (SOD) and albumin decreased in the PM-exposed groups although neuronal morphology and other serum indicators did not show significant difference between PM and FA groups. Moreover, PM induced the increase of plasminogen at 2 months but recovered at 4 months and then increased at 6 months again. The results from protein expression and transcriptomic test demonstrated that PI3K/AKT/FoxO1 pathway might be activated after 6-month PM exposure in mice. Indicators albumin, the percentage of albumin over IgG (A/G value), and plasminogen were the main serous changes in mice after early-stage (2 months) and long-term (6 months) PM exposure. In addition, early-stage injury induced by PM might recover at later time point and display significant injury again with the exposure time. PM exposure-induced brain injury might be associated with the activation of PI3K/AKT/FoxO1 pathway.