The leading role of adsorbed lead in PM2.5-induced hippocampal neuronal apoptosis and synaptic damage

Neurodegenerative diseases may be caused by air pollution, such as PM2.5. However, particles still need to be elucidated the mechanism of synergistic neurotoxicity induced by pollutant-loading PM2.5. In this study, we used a reductionist approach to study leading role of lead (Pb) in PM2.5-induced hippocampal neuronal apoptosis and synaptic damage both in vivo and in vitro. Pb in PM2.5 caused neurotoxicity: 1) by increasing ROS levels and thus causing apoptosis in neuronal cells and 2) by decreasing the expression of PSD95 via interfering with the calcium signaling pathway through cAMP/CREB/pCREB/BDNF/PSD95 pathway and reducing the synapse length by 50%. This study clarifies a key factor in PM2.5-induced neurotoxicity and provides the experimental basis for reducing PM2.5-induced neurotoxicity. [Display omitted] •Pb is the key factor of PM2.5-induced hippocampal neuron toxicity.•Pb dictates PM2.5-induced neuronal cytotoxicity by the ROS mediated apoptosis.•Pb dictates PM2.5-induced synaptic damage by interfering Ca2+ signaling and inhibiting the pathway of PSD95 expression.