The effects of particulate matter (PMs) from different cities on the nervous system remain unclear. In this study, aqueous solutions of 0.45 μm membrane-filtered PM from 31 major Chinese cities were intravenously administered to rats. Neurotoxicity and mechanisms were investigated by quantifying rat behavior, analyzing  in vivo biomarkers, and examining the PM physicochemical properties. PMs from different cities had variable impacts on rat responses, as manifested by the movement speed of the right ear, particularly at 1 h and 4–6 days postexposure. Physiological mechanisms were linked to the regulation of glucocorticoids via the hypothalamic-pituitary-adrenal axis and miR-107/miR-124 expression in the blood. Additionally, PM toxicity was strongly influenced by particle morphology, size, and zeta potential, which varied greatly across cities. Using random forest and multiple linear regression, we revealed that PM particle sizes (458.67 and 531.17 nm) and PM zeta potentials (−3.78, −17.01, and −20.31 mV) had the most important impacts on rat responsiveness, which was in line with blood biomarkers levels in rats such as Glucocorticoid, IL-1β, and IFN-α. These findings indicate that PMs from 31 cities contribute to varying neurotoxicity, thus presenting a possible differential burden on Alzheimer’s disease in the aging population across many different regions.

https://pubs.acs.org/doi/10.1021/acs.est.4c10408