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Author Notes:

Correspondence: W. Michael Caudle, Department of Environmental Health, Rollins School of Public Health, Emory University, 2033 Claudia Nance Rollins Building, 1518 Clifton Rd, Atlanta, GA 30322-3090; Tel: (404) 712-8432; Fax: (404) 727-8744; Email: william.m.caudle@emory.edu

Acknowledgments: We would like to gratefully acknowledge Dr. Malu Tansey and her laboratory for assistance with developing the mesencepahlic primary culture protocol.

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Research Funding:

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:

  • Polybrominated diphenyl ethers
  • dopamine
  • striatum
  • vesicular monoamine transporter 2
  • DE-71
  • Parkinson’s disease

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

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Journal Title:

Experimental Neurology

Volume:

Volume 241

Publisher:

, Pages 138-147

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2012 Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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