Although there is evidence that exposure to ground-level ozone (O3) may cause an increased risk of neurological disorders (e.g., autistic spectrum disorder), low-dose chronic ozone exposure and its adverse effects on the nervous system have not been fully understood. Here, we evaluated the potential neurotoxic effects of long-term exposure to environmentally relevant O3 concentration (200 μg/m3 via a whole-body inhalation system, 12 h/day for 5 days/week) using a susceptible mouse model of autism induced by valproic acid. Various indicators of oxidative stress, mitochondria, and synapse in the brain tissues were then measured to determine the overall damage of O3 to the mouse brain. The results showed an aggravated risk of autism in mice offspring, which was embodied in decreased antioxidant contents, disturbed energy generation in mitochondria, as well as reduced expressions of protein kinase Mζ (PKMζ) and synaptic proteins [e.g., Synapsin 1 (SYN 1), postsynaptic density protein-95 (PSD-95)]. Overall, our study indicates that prenatal exposure to environmentally relevant O3 may exacerbate the symptoms of autism, shedding light on possible molecular mechanisms and providing valuable insights into the pathogenesis of autism, especially concerning low-dose levels of those pollutants.
Keywords: autistic spectrum disorder; environmental exposure; ozone; pathogenesis; valproic acid.