Exposure to PM2.5 induces neurotoxicity, mitochondrial dysfunction, oxidative stress and inflammation in human SH-SY5Y neuronal cells

Ambient air pollution is a global public health issue. Recent evidence suggests that exposure to fine aerosolized particulate matter (PM) as small as <= 2.5 microns (PM2.5) is neurotoxic to brain structures. Many studies also suggest exposure to PM2.5 may cause neurotoxicity and affect brain function. However, the molecular mecha-nisms by which PM2.5 exerts these effects are not fully understood. Thus, we evaluated the hypothesis that PM2.5 exposure exerts its neurotoxic effects via increased oxidative and inflammatory cellular damage and mito-chondrial dysfunction using human SH-SY5Y neuronal cells. Here, we show PM2.5 exposure significantly de-creases viability, and increases caspase 3 and 9 protein expression and activity in SH-SY5Y cells. In addition, PM2.5 exposure decreases SH-SY5Y survival, disrupts cell and mitochondrial morphology, and significantly de-creases ATP levels, D-loop levels, and mitochondrial mass and function (maximal respiratory function, COX activity, and mitochondrial membrane potential) in SH-SY5Y cells. Moreover, SH-SY5Y cells exposed to PM2.5 have significantly decreased mRNA and protein expression levels of survival genes (CREB and Bcl-2) and neu-roprotective genes (PPAR gamma and AMPK). We further show SH-SY5Y cells exposure to PM2.5 induces significant increases in the levels of oxidative stress, and expression levels of the inflammatory mediator's TNF-alpha, IL-113, and NF-kappa B. Taken together, these results provide the first evidence of the biochemical, molecular and morphological effects of PM2.5 on human neuronal SH-SY5Y cells, and support our hypothesis that increased mitochondrial disruption, oxidative stress and inflammation are critical mediators of its neurotoxic effects. These findings further improve our understanding of the neuronal cell impact of PM2.5 exposure, and may be useful in the design of strategies for the treatment and prevention of human neurodegenerative disorders.