PM₁₀ Exposure Induced Neuronal Degenerative Injury And Systemic Inflammation Mechanism

With the rapid development of the industrialization, the fuel combustion and transportation brought serious atmospheric particulate matter pollution. Increasing studies showed that particulate matter pollution might be associated with cardiovascular diseases, and may pose negative impacts on central nervous system as well. Large amounts of epidemiological studies also indicated that there existed a significant correlation between atmospheric particulate matter pollution and neurodegeneration. A recognized mechanism of how particulate matter induced cognitive impairment was that particulate matter promoted neuroinflammation through system inflammation, finally leading to a series of cognitive damage. But related researches focused only on epidemiology, little experimental models existed to explore the nervous system damage brought by particulate matter.In the study, firstly, primary cultured hippocampal neurons at different Day in vitro (DIV 4,7 and 14) were treated with different concentrations of PM10 collected from heating season for 6 hours. The mRNA levels of glial markers (CD 14, CD68 and GFAP) and inflammation related factors (IL-1β and ICAM-1) in neurons were determined. The results showed that the mRNA levels of these factors significantly increased after exposure to different concentrations of PM10, which indicated that PM10 caused significantly inflammatory responses in neurons.Secondly, primary cultured hippocampal neurons at DIV 4,7 and 14 were exposed to different concentrations of PM10 collected from heating season for 24 hours. The mRNA levels of synaptic receptors (NR1, NR2A, NR2B, AMPA1 and AMPA2) in neurons were determined. Following this, neurons at DIV 7 were exposed to single PM10 as well as both PM10 and vitamin c (Vc), and the protein levels of synaptic receptors were detected. The results showed that the mRNA levels of synaptic receptors in neurons at DIV 4 were unregulated, while that in neurons at DIV 7 and DIV 14 were decreased, and the effects imposed by PM10 were obvious in neurons at DIV 4 and DIV 7 compared with those in DIV 14. Exposure to PM10 alone reduced the protein expressions of synaptic receptors, but their levels recovered after adding Vc. The results suggested that the effects on synaptic plasticity imposed by PM10 were different in different stages of neurons, manifesting excitotoxicity in early stages while degenerative injury in later stages. Neurons in early and middle stages were more sensitive to the toxicity of PM10 than those in later stages. Antioxidant Vc could protect neurons from damage of PM10.Finally, Wistar rats were treated with PM10 by intratracheal instillation at different concentrations from heating season and different seasons of PM10 at the same concentration. The histological change in the heart and the mRNA expressions of inflammation-related factors (IL-1β, ICAM-1, COX-2 and iNOS) and apoptosis related factor (p53) in the lung and heart of rats were analyzed. The results indicated that PM10 from spring and winter at higher concentrations induced increased expressions of inflammatory factors in rat lung and heart, which was further confirmed by HE observation in heart. All the results implied that PM10 exposure might lead to inflammatory responses in rat lung and heart, and the effects showed concentration and season-dependent manners.