Investigating the neurotoxic effects of perfluoroalkyl substances (PFASs) in human dopaminergic neurons

The increasing environmental spreading of perfluoroalkyl substances (PFASs) raises concerns for theirimpact on human health. PFASs are synthetic chemicals widely used in industrial and consumerproducts to make surfaces repellent to water and lipids. Once ingested or inhaled, PFASs arebioaccumulated in the blood, liver, kidney, and brain of various species with an elimination half-lifein humans of 3-5 years. In a previous publication, we highlighted for the first time that theaccumulation of PFASs can alter the development of human dopaminergic neurons (Di Nisio et al.,2022). This finding, together with the discovery of massive PFAS accumulation in the substantia nigraof the human brain, suggests a possible link with the onset of neurodevelopment defects andParkinson’s disease in highly PFAS contaminated areas. In the present work, we investigated thefunctional alterations of dopaminergic neurons upon exposure to PFOA, one of the most common andharmful PFAS. Two in vitro human models were tested: neuron-differentiated induced pluripotentstem cells (iPSCs) and LUHMES cells, a stable cell line isolated from the mesencephalon. We observedsignificant modifications of the electrophysiological and calcium (Ca 2+ ) activities in both cell linesthat were PFAS-dose and –administration time dependent. The results were supported by the analysisof morphological and protein expression markers.