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Alteration to Dopaminergic Synapses Following Exposure to Perfluorooctane Sulfonate (PFOS), in Vitro and in Vivo

Our understanding of the contribution exposure to environmental toxicants has on neurological disease continues to evolve. Of these, Parkinson’s disease (PD) has been shown to have a strong environmental component to its etiopathogenesis. However, work is still needed to identify and characterize en...

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Autores principales: Patel, Rahul, Bradner, Joshua M., Stout, Kristen A., Caudle, William Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5635798/
https://www.ncbi.nlm.nih.gov/pubmed/29083377
http://dx.doi.org/10.3390/medsci4030013
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author Patel, Rahul
Bradner, Joshua M.
Stout, Kristen A.
Caudle, William Michael
author_facet Patel, Rahul
Bradner, Joshua M.
Stout, Kristen A.
Caudle, William Michael
author_sort Patel, Rahul
collection PubMed
description Our understanding of the contribution exposure to environmental toxicants has on neurological disease continues to evolve. Of these, Parkinson’s disease (PD) has been shown to have a strong environmental component to its etiopathogenesis. However, work is still needed to identify and characterize environmental chemicals that could alter the expression and function of the nigrostriatal dopamine system. Of particular interest is the neurotoxicological effect of perfluorinated compounds, such as perfluorooctane sulfonate (PFOS), which has been demonstrated to alter aspects of dopamine signaling. Using in vitro approaches, we have elaborated these initial findings to demonstrate the neurotoxicity of PFOS to the SH-SY5Y neuroblastoma cell line and dopaminergic primary cultured neurons. Using an in vivo model, we did not observe a deficit to dopaminergic terminals in the striatum of mice exposed to 10 mg/kg PFOS for 14 days. However, subsequent exposure to the selective dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) significantly reduced the expression of dopamine transporter (DAT) and tyrosine hydroxylase (TH), and resulted in an even greater reduction in DAT expression in animals previously exposed to PFOS. These findings suggest that PFOS is neurotoxic to the nigrostriatal dopamine circuit and this neurotoxicity could prime the dopamine terminal to more extensive damage following additional toxicological insults.
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spelling pubmed-56357982017-10-26 Alteration to Dopaminergic Synapses Following Exposure to Perfluorooctane Sulfonate (PFOS), in Vitro and in Vivo Patel, Rahul Bradner, Joshua M. Stout, Kristen A. Caudle, William Michael Med Sci (Basel) Article Our understanding of the contribution exposure to environmental toxicants has on neurological disease continues to evolve. Of these, Parkinson’s disease (PD) has been shown to have a strong environmental component to its etiopathogenesis. However, work is still needed to identify and characterize environmental chemicals that could alter the expression and function of the nigrostriatal dopamine system. Of particular interest is the neurotoxicological effect of perfluorinated compounds, such as perfluorooctane sulfonate (PFOS), which has been demonstrated to alter aspects of dopamine signaling. Using in vitro approaches, we have elaborated these initial findings to demonstrate the neurotoxicity of PFOS to the SH-SY5Y neuroblastoma cell line and dopaminergic primary cultured neurons. Using an in vivo model, we did not observe a deficit to dopaminergic terminals in the striatum of mice exposed to 10 mg/kg PFOS for 14 days. However, subsequent exposure to the selective dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) significantly reduced the expression of dopamine transporter (DAT) and tyrosine hydroxylase (TH), and resulted in an even greater reduction in DAT expression in animals previously exposed to PFOS. These findings suggest that PFOS is neurotoxic to the nigrostriatal dopamine circuit and this neurotoxicity could prime the dopamine terminal to more extensive damage following additional toxicological insults. MDPI 2016-08-16 /pmc/articles/PMC5635798/ /pubmed/29083377 http://dx.doi.org/10.3390/medsci4030013 Text en © 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Patel, Rahul
Bradner, Joshua M.
Stout, Kristen A.
Caudle, William Michael
Alteration to Dopaminergic Synapses Following Exposure to Perfluorooctane Sulfonate (PFOS), in Vitro and in Vivo
title Alteration to Dopaminergic Synapses Following Exposure to Perfluorooctane Sulfonate (PFOS), in Vitro and in Vivo
title_full Alteration to Dopaminergic Synapses Following Exposure to Perfluorooctane Sulfonate (PFOS), in Vitro and in Vivo
title_fullStr Alteration to Dopaminergic Synapses Following Exposure to Perfluorooctane Sulfonate (PFOS), in Vitro and in Vivo
title_full_unstemmed Alteration to Dopaminergic Synapses Following Exposure to Perfluorooctane Sulfonate (PFOS), in Vitro and in Vivo
title_short Alteration to Dopaminergic Synapses Following Exposure to Perfluorooctane Sulfonate (PFOS), in Vitro and in Vivo
title_sort alteration to dopaminergic synapses following exposure to perfluorooctane sulfonate (pfos), in vitro and in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5635798/
https://www.ncbi.nlm.nih.gov/pubmed/29083377
http://dx.doi.org/10.3390/medsci4030013
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