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ToxSci Advance Access published online on May 15, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl018
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received February 21, 2006
Accepted March 25, 2006

Neurotoxicology

Polychlorinated Biphenyl (PCB)-Induced Reduction of Dopamine Transporter Expression as a Precursor to Parkinson's Disease-associated Dopamine Toxicity

W. Michael Caudle 1, Jason R. Richardson 2, Kristin C. Delea 1, Thomas S. Guillot 1, Minzheng Wang 1, Kurt D. Pennell 3, and Gary W. Miller Ph.D. 1 *

1 Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322; Department of Environmental and Occupational Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322
2 Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322; Department of Environmental and Occupational Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322; Environmental and Occupational Health Sciences Institute and Department of Environmental and Occupational Medicine, University of Medicine and Dentistry-New Jersey/Robert Wood Johnson Medical School, Piscataway, NJ 08854
3 School of Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta, GA 30332

* To whom correspondence should be addressed.
Gary W. Miller, E-mail: gary.miller{at}emory.edu


  Abstract

Epidemiological and laboratory studies have suggested that exposure to polychlorinated biphenyls (PCBs) may be a risk factor for Parkinson's disease. The purpose of this study was to examine the potential mechanisms by which PCBs may disrupt normal functioning of the nigrostriatal dopamine system. We utilized an environmentally-relevant exposure of PCBs (7.5 or 15 mg/kg/day Aroclor 1254:1260 for 30 days by oral gavage) to identify early signs of damage to the dopamine system. This dosing regimen, which resulted in PCB levels similar to those found in human brain samples, did not cause overt degeneration to the dopamine system as shown by a lack of change in striatal dopamine levels or tyrosine hydroxylase levels. However, we did observe a dramatic dose-dependent decrease in striatal dopamine transporter (DAT) levels. The observed reductions appear to be specific to the dopamine transporter populations located in the striatum, as no change was observed in other dopaminergic brain regions or to other neurotransmitter transporters present in the striatum. These data demonstrate that PCB tissue concentrations similar to those found in post-mortem human brain specifically disrupt dopamine transport, which acts as a precursor to subsequent damage to the dopamine system. Furthermore, DAT imaging may be useful in evaluating alterations in brain function in human populations exposed to PCBs.


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