PM2.5 can Promote the Alzheimer's Disease-like Changes through Microglia Related Mechanism in Mice

Abstract

Background: PM2.5, the main particulate air pollutant, poses serious hazard to human health. Alzheimer's disease (AD) is a major neurodegenerative disease characterized by amyloid plaques and neurofibrillary tangles. Recent studies reported that PM could promote AD-like pathologies in human brain. However, the mechanism of PM2.5-induced AD-like changes is still unclear and more investigations are needed for further understanding.Methods: In this study, we established experimental model of long-term PM2.5 exposure with young/old wildtype C57BL/6 and APP/PS transgenic mice. Behavior assessments were monitored after four weeks of exposure. The changes of blood cells were detected by Complete Blood Count and splenic macrophages were detected by flow cytometry. Immunohistochemical staining was used to observe the damage of PM2.5 on neurons, the deposition of Aβ and the changes of microglia. RNA-seq was used to analyze the whole genome changes of hippocampus after PM2.5 exposure. In addition, microglia related genes were analyzed via Real-time PCR. Results: After mice were exposed to PM2.5 for a month, some AD-like behavioral changes, such as learning and memory impairment were detected especially in old and transgenic mice. The histopathological changes, such as β-amyloid (Aβ) deposition, morphological changes of microglia, as well as great impairments of hippocampus neurons but not cortex neurons were observed. The analyze of whole-genome expression in the hippocampus suggested long term PM2.5 exposure changed the expression of genes related with AD process (mouse behavior and microglia differentiation). Furthermore, the mRNA level, which related to microglia, of CD86, CD22, IL-1β was upregulated and CD206, TREM2, TGF-β2 was downregulated. Conclusions: Aged population were more susceptible to long-term PM2.5 exposure and PM2.5 could promote AD-like phenotype through microglia related mechanism.