LAUSR

PM2.5 exposure is considered harmful to central nerve system, while the specific biochemical mechanism underlying is still unrevealed. Neuronal apoptosis is believed the crucial event in pathogenesis of neurodegenerative diseases, but evidence supporting neuronal apoptosis as the mechanism for PM2.5 exposure induced neuronal injury is insufficient. S-adenosylmethionine decarboxylase 1 (AMD1) and its related spermidine synthesis have been shown to associate with cellular apoptosis, but its role in PM2.5 exposure induced neuronal apoptosis was rarely reported. The current study was aimed to better understand contribution of AMD1 activity and spermidine in PM2.5 exposure induced neuronal apoptosis. Sixteen C57BL/6 male mice were randomly divided and kept into ambient PM2.5 chamber or filtered air chamber for 6 months to establish the mouse model of whole-body ambient PM2.5 chronic exposure. In parallel, PC12 cells and primary hippocampal neurons were applied for various concentrations of PM2.5 treatment (0, 25, 50, 100, 200, and 400 μg/mL) to explore the possible cellular and molecular mechanism which may be critically involved in the process. Results showed that PM2.5 exposure triggered neuronal apoptosis with increased expression of Bax/Bcl-2 and cleaved caspase-3. PM2.5 exposure reduced AMD1 expression and spermidine synthesis. AMD1 inhibition could mimic PM2.5 exposure induced neuronal apoptosis. Spermidine supplementation rescued against neurotoxicity and inhibited PM2.5 induced apoptosis via impaired depolarization of mitochondrial membrane potential and reduced mitochondrial apoptosis related proteins. In summary, our work demonstrated that exposure to PM2.5 led to neuronal apoptosis, which may be the key event in the process of air pollution induced neurodegenerative diseases. AMD1 and spermidine associated with neuronal apoptosis induced by PM2.5 exposure, which was at least partially dependent on mitochondria mediated pathway.