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

• Type of Material: Article
• Authors: Rahul Patel, Emory University; Joshua M. Bradner, Emory University; Kristen A. Stout, Emory University; William Michael Caudle, Emory University
• Language: English
• Date: 2016-08-16
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2016 by the authors. Licensee MDPI, Basel, Switzerland.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/medsci4030013
• Title of Journal or Parent Work: Med Sci (Basel)
• Volume: 4
• Issue: 3
• Grant/Funding Information: This work was supported by National Institutes of Health grant R00ES017477 to W.M.C.
• Keywords: tyrosine hydroxylase; dopamine transporter; vesicular monoamine transporter 2; perfluorooctane sulfonate; striatum
• Research Categories: Biology, Neuroscience; Health Sciences, Public Health; Environmental Sciences

Abstract

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.