Chronic di(2-ethylhexyl) phthalate exposure leads to dopaminergic neuron degeneration through mitochondrial...

The plasticizer di(2-ethylhexyl) phthalate (DEHP) is frequently detected in the environment due to the abundance of its use. These levels might be hazardous to human health and ecosystems. Phthalates have been associated with neurological disorders, yet whether chronic DEHP exposure plays a role in Parkinson's disease (PD) or its underlying mechanisms is unknown. We investigated the effects of chronic DEHP exposure less than an environmentally-relevant dose on PD hallmarks, using Caenorhabditis elegans as a model. We show that developmental stage and exposure timing influence DEHP-induced dopaminergic neuron degeneration. In addition, in response to chronic DEHP exposure at 5 mg/L, mitochondrial fragmentation became significantly elevated, reactive oxygen species (ROS) levels increased, and ATP levels decreased, suggesting that mitochondrial dysfunction occurs. Furthermore, the data show that mitochondrial complex I (nuo-1 and gas-1) and complex II (mev-1) are involved in DEHP-induced dopaminergic neuron toxicity. These results suggest that chronic exposure to DEHP at levels less than an environmentally-relevant dose causes dopaminergic neuron degeneration through mitochondrial dysfunction involving mitochondrial complex I and II. Considering the high level of genetic conservation between C. elegans and mammals, chronic DEHP exposure might elevate the risk of developing PD in humans.