Polychlorinated biphenyl-induced reduction of dopamine transporter expression as a precursor to Parkinson's disease-associated dopamine toxicity.
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 1,254:1,260 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.
Caudle
W Michael
WM
Department of Environmental and Occupational Health, Rollins School of Public Health and Center for Neurodegenerative Disease, School of Medicine, Emory University, Atlanta, Georgia 30322-3090, USA.
Richardson
Jason R
JR
Delea
Kristin C
KC
Guillot
Thomas S
TS
Wang
Minzheng
M
Pennell
Kurt D
KD
Miller
Gary W
GW
D000818:Animals; D001140:Aroclors / Q000493:pharmacokinetics / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D020111:Chlorodiphenyl (54% Chlorine) / Q000493:pharmacokinetics / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010300:Parkinson Disease / Q000209:etiology; D050493:Vesicular Monoamine Transport Proteins
D001140:Aroclors; D050483:Dopamine Plasma Membrane Transport Proteins; D004785:Environmental Pollutants; C493453:Slc18a2 protein, mouse; D050493:Vesicular Monoamine Transport Proteins; C026987:aroclor 1260; D020111:Chlorodiphenyl (54% Chlorine); D004298:Dopamine