Impairment of human dopaminergic neurons at different developmental stages by perfluoro-octanoic acid (PFOA) and differential human brain areas accumulation of perfluoroalkyl chemicals

• DOI: 10.1016/j.envint.2021.106982
• Publication Date: 2021-11-12T17:25:29Z
• Authors: Andrea Di Nisio; Micaela Pannella; Stefania Vogiatzis; Stefania Sut; Stefano Dall'Acqua; Maria Santa Rocca; Angelo Antonini; Andrea Porzionato; Raffaele De Caro; Mario Bortolozzi; Luca De Toni; Carlo Foresta
• Keywords: Reuptake; Human brain; Monoaminergic; Neurotoxicity

Perfluoroalkyl substances (PFASs) are synthetic chemicals widely used in industrial and consumer products. The environmental spreading of PFASs raises concerns for their impact on human health. In particular, the bioaccumulation humans due to exposure has been reported also total brain samples PFAS associated with neurodevelopmental disorders. this study we aimed investigate specific different areas. Our data major accumulation brainstem region, which is richly populated by dopaminergic neurons (DNs), autopsy from people resident a PFAS-polluted area Italy. Since DNs main source dopamine (DA) mammalian central nervous system (CNS), evaluated possible functional consequences perfluoro-octanoic acid (PFOA) model obtained differentiation induced pluripotent stem cells (hiPSCs). Particularly, analyzed effect PFOA 24 h, at concentration 10 ng/ml, 3 steps differentiation: neuronal commitment phase (DP1), precursor (DP2) mature (DP3). Interestingly, compared untreated cells, was reduced expression Tyrosine Hydroxylase (TH) Neurofilament Heavy (NFH), both markers maturation DP2 phase. addition, DP3 exposed showed severe reduction Dopamine Transporter (DAT), functionally involved pre-synaptic reuptake. proof-of-concept show significant exposure, mainly most sensitive stage neural differentiation, prompting way further investigations more directly relevant risk assessment these chemicals.