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

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 in humans due to environmental exposure has been reported also in total...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Perfluoroalkyl substances Central Nervous System Dopaminergic neuron Human Induced Pluripotent stem (h-iPS) cells Tyrosine Hydroxylase Dopamine Transporter Environmental sciences GE1-350
Acceso en línea:	https://doaj.org/article/3b2a92a2b13547a589757df1b9a4dde6
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spelling	oai:doaj.org-article:3b2a92a2b13547a589757df1b9a4dde62021-11-14T04:28:29ZImpairment of human dopaminergic neurons at different developmental stages by perfluoro-octanoic acid (PFOA) and differential human brain areas accumulation of perfluoroalkyl chemicals0160-412010.1016/j.envint.2021.106982https://doaj.org/article/3b2a92a2b13547a589757df1b9a4dde62022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0160412021006073https://doaj.org/toc/0160-4120Perfluoroalkyl 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 in humans due to environmental exposure has been reported also in total brain samples and PFAS exposure has been associated with neurodevelopmental disorders. In this study we aimed to investigate the specific PFAS bioaccumulation in different brain areas. Our data reported major accumulation in the brainstem region, which is richly populated by dopaminergic neurons (DNs), in brain autopsy samples from people resident in a PFAS-polluted area of Italy.Since DNs are the main source of dopamine (DA) in the mammalian central nervous system (CNS), we evaluated the possible functional consequences of perfluoro-octanoic acid (PFOA) exposure in a human model of DNs obtained by differentiation of human induced pluripotent stem cells (hiPSCs). Particularly, we analyzed the specific effect of the exposure to PFOA for 24 h, at the concentration of 10 ng/ml, at 3 different steps of dopaminergic differentiation: the neuronal commitment phase (DP1), the neuronal precursor phase (DP2) and the mature dopaminergic differentiation phase (DP3). Interestingly, compared to untreated cells, exposure to PFOA was associated with a reduced expression of Tyrosine Hydroxylase (TH) and Neurofilament Heavy (NFH), both markers of dopaminergic maturation at DP2 phase. In addition, cells at DP3 phase exposed to PFOA showed a severe reduction in the expression of the Dopamine Transporter (DAT), functionally involved in pre-synaptic dopamine reuptake.In this proof-of-concept study we show a significant impact of PFOA exposure, mainly on the most sensitive stage of neural dopaminergic differentiation, prompting the way for further investigations more directly relevant to risk assessment of these chemicals.Andrea Di NisioMicaela PannellaStefania VogiatzisStefania SutStefano Dall'AcquaMaria Santa RoccaAngelo AntoniniAndrea PorzionatoRaffaele De CaroMario BortolozziLuca De ToniCarlo ForestaElsevierarticlePerfluoroalkyl substancesCentral Nervous SystemDopaminergic neuronHuman Induced Pluripotent stem (h-iPS) cellsTyrosine HydroxylaseDopamine TransporterEnvironmental sciencesGE1-350ENEnvironment International, Vol 158, Iss , Pp 106982- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Perfluoroalkyl substances Central Nervous System Dopaminergic neuron Human Induced Pluripotent stem (h-iPS) cells Tyrosine Hydroxylase Dopamine Transporter Environmental sciences GE1-350
spellingShingle	Perfluoroalkyl substances Central Nervous System Dopaminergic neuron Human Induced Pluripotent stem (h-iPS) cells Tyrosine Hydroxylase Dopamine Transporter Environmental sciences GE1-350 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 Impairment of human dopaminergic neurons at different developmental stages by perfluoro-octanoic acid (PFOA) and differential human brain areas accumulation of perfluoroalkyl chemicals
description	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 in humans due to environmental exposure has been reported also in total brain samples and PFAS exposure has been associated with neurodevelopmental disorders. In this study we aimed to investigate the specific PFAS bioaccumulation in different brain areas. Our data reported major accumulation in the brainstem region, which is richly populated by dopaminergic neurons (DNs), in brain autopsy samples from people resident in a PFAS-polluted area of Italy.Since DNs are the main source of dopamine (DA) in the mammalian central nervous system (CNS), we evaluated the possible functional consequences of perfluoro-octanoic acid (PFOA) exposure in a human model of DNs obtained by differentiation of human induced pluripotent stem cells (hiPSCs). Particularly, we analyzed the specific effect of the exposure to PFOA for 24 h, at the concentration of 10 ng/ml, at 3 different steps of dopaminergic differentiation: the neuronal commitment phase (DP1), the neuronal precursor phase (DP2) and the mature dopaminergic differentiation phase (DP3). Interestingly, compared to untreated cells, exposure to PFOA was associated with a reduced expression of Tyrosine Hydroxylase (TH) and Neurofilament Heavy (NFH), both markers of dopaminergic maturation at DP2 phase. In addition, cells at DP3 phase exposed to PFOA showed a severe reduction in the expression of the Dopamine Transporter (DAT), functionally involved in pre-synaptic dopamine reuptake.In this proof-of-concept study we show a significant impact of PFOA exposure, mainly on the most sensitive stage of neural dopaminergic differentiation, prompting the way for further investigations more directly relevant to risk assessment of these chemicals.
format	article
author	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
author_facet	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
author_sort	Andrea Di Nisio
title	Impairment of human dopaminergic neurons at different developmental stages by perfluoro-octanoic acid (PFOA) and differential human brain areas accumulation of perfluoroalkyl chemicals
title_short	Impairment of human dopaminergic neurons at different developmental stages by perfluoro-octanoic acid (PFOA) and differential human brain areas accumulation of perfluoroalkyl chemicals
title_full	Impairment of human dopaminergic neurons at different developmental stages by perfluoro-octanoic acid (PFOA) and differential human brain areas accumulation of perfluoroalkyl chemicals
title_fullStr	Impairment of human dopaminergic neurons at different developmental stages by perfluoro-octanoic acid (PFOA) and differential human brain areas accumulation of perfluoroalkyl chemicals
title_full_unstemmed	Impairment of human dopaminergic neurons at different developmental stages by perfluoro-octanoic acid (PFOA) and differential human brain areas accumulation of perfluoroalkyl chemicals
title_sort	impairment of human dopaminergic neurons at different developmental stages by perfluoro-octanoic acid (pfoa) and differential human brain areas accumulation of perfluoroalkyl chemicals
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/3b2a92a2b13547a589757df1b9a4dde6
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Impairment of human dopaminergic neurons at different developmental stages by perfluoro-octanoic acid (PFOA) and differential human brain areas accumulation of perfluoroalkyl chemicals

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