Urban PM0.2 Affects Mouse Astrocytes

Air pollution is the largest environmental risk factor that has lately been linked to neurodegenerative diseases. Several studies demonstrated that pollutant exposure leads to neuroinflammation, oxidative stress, and the appearance of protein aggregates in the brain, yet little is known about the adverse effects induced in specific brain cell types. Here, we aimed to decipher how nanoscale particulate matter (PM0.2, with an aerodynamic diameter less than 0.2 µm) collected from urban air in China affects a central element of the brain's homeostatic system – the astrocytes. In real-life conditions, this small size allows particles to better translocate to the brain when inhaled. mRNA sequencing data demonstrate that PM0.2 triggers activation of the antioxidative stress signalling and detoxification system in exposed astrocytes, indicating activation of the cellular protection system. Overall, we found 2217 genes to be differently expressed when PM0.2-exposed astrocytes were compared to vehicle-treated control cells. The most activated canonical pathways were xenobiotic metabolism, the Nrf2 oxidative stress response, and glutathione-mediated detoxification. Shotgun proteomics on PM0.2-treated astrocytes corroborated the observed gene expression alterations. A comparison of our results with previously obtained mRNA sequencing data on PM-exposed microglia and the mouse cerebral cortex revealed both similar and distinct responses of astrocytes to PM. Our results provide insight into astrocyte-specific responses to urban air pollutant exposure and allow a better understanding of the processes activated by PM exposure in the brain.