ToxSci Advance Access originally published online on May 15, 2006
Toxicological Sciences 2006 92(2):490-499; doi:10.1093/toxsci/kfl018
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Polychlorinated Biphenyl–Induced Reduction of Dopamine Transporter Expression as a Precursor to Parkinson's Disease–Associated Dopamine Toxicity
,
,1
* Center for Neurodegenerative Disease, School of Medicine and Department of Environmental and Occupational Health, Rollins School of Public Health, Emory University, Atlanta, Georgia 30322-3090; 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, New Jersey 08854; and School of Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332
Received February 21, 2006; accepted March 25, 2006
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 (DA) 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 DA system. This dosing regimen, which resulted in PCB levels similar to those found in human brain samples, did not cause overt degeneration to the DA system as shown by a lack of change in striatal DA 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 DAT 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 postmortem human brain specifically disrupt DA transport, which acts as a precursor to subsequent damage to the DA system. Furthermore, DAT imaging may be useful in evaluating alterations in brain function in human populations exposed to PCBs.
Key Words: PCB; Parkinson's disease; dopamine; tyrosine hydroxylase; DAT.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. N. Taylor, W. M. Caudle, K. R. Shepherd, A. Noorian, C. R. Jackson, P. M. Iuvone, D. Weinshenker, J. G. Greene, and G. W. Miller Nonmotor Symptoms of Parkinson's Disease Revealed in an Animal Model with Reduced Monoamine Storage Capacity J. Neurosci., June 24, 2009; 29(25): 8103 - 8113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. M. Caudle, J. R. Richardson, M. Z. Wang, T. N. Taylor, T. S. Guillot, A. L. McCormack, R. E. Colebrooke, D. A. Di Monte, P. C. Emson, and G. W. Miller Reduced Vesicular Storage of Dopamine Causes Progressive Nigrostriatal Neurodegeneration J. Neurosci., July 25, 2007; 27(30): 8138 - 8148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Richardson, W. M. Caudle, T. S. Guillot, J. L. Watson, E. Nakamaru-Ogiso, B. B. Seo, T. B. Sherer, J. T. Greenamyre, T. Yagi, A. Matsuno-Yagi, et al. Obligatory Role for Complex I Inhibition in the Dopaminergic Neurotoxicity of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Toxicol. Sci., January 1, 2007; 95(1): 196 - 204. [Abstract] [Full Text] [PDF]
|
|