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

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 hexabromocyclododecane (HBCD) as a flame retardant in consumer products. The physiochemical similarities between HBCD and PBDEs suggest that HBCD may also be neurotoxic to the dopamine system. The purpose of this study was to assess the neurotoxicity of HBCD on the nigrostriatal dopamine system using an in vitro and in vivo approach. We demonstrate that HBCD causes significant cell death in a dopaminergic cell line, as well as reductions in the growth and viability of TH+ primary cultured neurons. Assessment of the in vivo neurotoxicity of HBCD resulted in significant reductions in the expression of the striatal dopamine transporter (DAT) and VMAT2, both of which are integral in mediating dopamine homeostasis and neurotransmission in the dopamine circuit. However, no changes were seen in the expression of TH in the dopamine terminal, or striatal levels of dopamine. To date, these are the first data to demonstrate that exposure to HBCD disrupts the nigrostriatal dopamine system. Given these results and the ubiquitous nature of HBCD in the environment, its possible role as an environmental risk factor for Parkinson disease should be further investigated.

Table of Contents

Introduction.............................................................1

Materials and Methods.............................................4

Results......................................................................9

Discussion...............................................................12

Figures.....................................................................18

References...............................................................23

Appendix.................................................................26

About this Master's Thesis

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School	Rollins School of Public Health
Department	Environmental Health
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Biology, Neuroscience Health Sciences, Public Health Health Sciences, Toxicology
Parola chiave	Vesicular Monoamine Transporter 2 Dopamine Transporter Parkinson Disease Hexabromocyclododecane Dopamine Neurotoxicity
Committee Chair / Thesis Advisor	Caudle, William Michael, Emory University
Committee Members	Tolbert, Paige, Emory University
Partnering Agencies	Emory University schools, faculty or affiliated programs

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