Search

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.

PM2.5 particles in air pollution have been widely considered associated with respiratory and cardiovascular diseases. Recent studies have shown that PM2.5 can also cause central nervous system (CNS) diseases, including a variety of neurodegenerative diseases, such as Alzheimer's disease (AD). Activation of microglia in the central nervous system can lead to inflammatory and neurological damage. PM2.5 will reduce the methylation level of DNA and affect epigenetics. PM2.5 enters the human body through a variety of pathways to have pathological effects on CNS. For example, PM2.5 can destroy the integrity of the blood-brain barrier (BBB), so peripheral systemic inflammation easily crosses BBB and reaches CNS. The olfactory nerve is another way for PM2.5 particles to enter the brain. Surprisingly, PM2.5 can also enter the gastrointestinal tract, causing imbalances in the intestinal microecology to affect central nervous system diseases. The current work collected and discuss the mechanisms of PM2.5-induced CNS damage and PM2.5-induced neurodegenerative diseases.