Selective damage to dopaminergic transporters following exposure to the brominated flame retardant, HBCDD

• Type of Material: Article
• Authors: Kelly R. Genskow, Emory University; Joshua M. Bradner, Emory University; Muhammad M. Hossain, Robert Wood Johnson Medical School; Jason R. Richardson, Robert Wood Johnson Medical School; William Caudle, Emory University
• Language: English
• Date: 2015-11-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ntt.2015.06.003
• Title of Journal or Parent Work: Neurotoxicology and Teratology
• ISSN: 0892-0362
• Volume: 52
• Issue: Pt B
• Start Page: 162
• End Page: 169
• Grant/Funding Information: This work was supported by National Institutes of Health grants R00 ES017477 (WMC), P30 ES019776 (WMC), RO1 ES021800 (JRR), and P30 ES005022 (JRR).
• Keywords: NEUROCHEMICAL DEFICITS; DEVELOPMENTAL EXPOSURE; Dopamine; Hexabromocyclododecane; DIPHENYL ETHER MIXTURE; Parkinson disease; Dopamine transporter; Toxicology; Science & Technology; NEONATAL EXPOSURE; Vesicular monoamine transporter 2; Neurotoxicity; Neurosciences; SPONTANEOUS BEHAVIOR; Life Sciences & Biomedicine; Neurosciences & Neurology; BASAL GANGLIA
• Research Categories: Biology, Neuroscience; Environmental Sciences; Health Sciences, Toxicology

Abstract

Over the last several decades, the use of halogenated organic compounds has become the cause of environmental and human health concerns. Of particular notoriety has been the establishment of the neurotoxicity of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). The subsequent banning of PBDEs has led to greatly increased use of 1,2,5,6,9,10-hexabromocyclododecane (HBCDD, also known as HBCD) as a flame retardant in consumer products. The physiochemical similarities between HBCDD and PBDEs suggest that HBCDD may also be neurotoxic to the dopamine system, which is specifically damaged in Parkinson disease (PD). The purpose of this study was to assess the neurotoxicity of HBCDD on the nigrostriatal dopamine system using an in vitro and in vivo approach. We demonstrate that exposure to HBCDD (0-25 μM) for 24 h causes significant cell death in the SK-N-SH catecholaminergic cell line, as well as reductions in the growth and viability of TH. + primary cultured neurons at lower concentrations (0-10 μM) after 72 h of treatment. Assessment of the in vivo neurotoxicity of HBCDD (25 mg/kg for 30 days) resulted in significant reductions in the expression of the striatal dopamine transporter and vesicular monoamine transporter 2, both of which are integral in mediating dopamine homeostasis and neurotransmission in the dopamine circuit. However, no changes were seen in the expression of tyrosine hydroxylase in the dopamine terminal, or striatal levels of dopamine. To date, these are the first data to demonstrate that exposure to HBCDD disrupts the nigrostriatal dopamine system. Given these results and the ubiquitous nature of HBCDD in the environment, its possible role as an environmental risk factor for PD should be further investigated.