Exposure to the Polybrominated Diphenyl Ether Mixture DE-71 Damages the Nigrostriatal Dopamine System: Role of Dopamine Handling in Neurotoxicity

• Type of Material: Article
• Authors: Joshua M. Bradner, Emory University; Tiffany A. Suragh, Emory University; W. Wyatt Wilson, Emory University; Carlos R. Lazo, Emory University; Kristen A. Stout, Emory University; Hye Mi Kim, Emory University; Min Z. Wang, Emory University; Douglas Walker, Tufts University; Kurt D. Pennell, Tufts University; Jason R. Richardson, Robert Wood Johnson Medical School; Gary W Miller, Emory University; William Michael Caudle, Emory University
• Language: English
• Date: 2013-03
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.expneurol.2012.12.013
• Title of Journal or Parent Work: Experimental Neurology
• ISSN: 0014-4886
• Volume: 241
• Start Page: 138
• End Page: 147
• Grant/Funding Information: This work was supported by National Institutes of Health grants [R00ES017477 to W.M.C.], [P01ES016731 to W.M.C., G.W.M., and K.D.P], [T32 ES012879 to G.W.M.], and [R01ES015991, P30ES005022, R21NS072097 to J.R.R.].
• Keywords: Parkinson’s disease; Polybrominated diphenyl ethers; striatum; DE-71; vesicular monoamine transporter 2; dopamine
• Research Categories: Health Sciences, Occupational Health and Safety; Biology, Neuroscience

Abstract

In the last several decades polybrominated diphenyl ethers (PBDEs) have replaced the previously banned polychlorinated biphenyls (PCBs) in multiple flame retardant utilities. As epidemiological and laboratory studies have suggested PCBs as a risk factor for Parkinson’s disease (PD), the similarities between PBDEs and PCBs suggest that PBDEs have the potential to be neurotoxic to the dopamine system. The purpose of this study was to evaluate the neurotoxic effects of the PBDE mixture, DE-71, on the nigrostriatal dopamine system and address the role of altered dopamine handling in mediating this neurotoxicity. Using an in vitro model system we found DE-71 effectively caused cell death in a dopaminergic cell line as well as reducing the number of TH+ neurons isolated from VMAT2 WT and LO animals. Assessment of DE-71 neurotoxicity in vivo demonstrated significant deposition of PBDE congeners in the brains of mice, leading to reductions in striatal dopamine and dopamine handling, as well as reductions in the striatal dopamine transporter (DAT) and VMAT2. Additionally, DE-71 elicited a significant locomotor deficit in the VMAT2 WT and LO mice. However, no change was seen in TH expression in dopamine terminal or in the number of dopamine neurons in the substantia nigra pars compacta (SNpc). To date, these are the first data to demonstrate that exposure to PBDEs disrupts the nigrostriatal dopamine system. Given their similarities to PCBs, additional laboratory and epidemiological research should be considered to assess PBDEs as a potential risk factor for PD and other neurological disorders.