Perinatal heptachlor exposure increases expression of presynaptic dopaminergic markers in mouse striatum.
Although banned in the 1970s, significant levels of the organochlorine pesticide heptachlor are still present in the environment raising concern over potential human exposure. In particular, organochlorine pesticides have been linked to an increased risk of Parkinson's disease. Studies from our laboratory and others have demonstrated that exposure of laboratory animals to heptachlor alters the levels and function of the dopamine transporter (DAT), an integral component of dopaminergic neurotransmission and a gateway for the dopaminergic neurotoxin MPTP. In this study, we examined the effects of developmental exposure to heptachlor on DAT, and other key components of the dopaminergic system, including the vesicular monoamine transporter 2 (VMAT2), tyrosine hydroxylase (TH), and aromatic amino acid decarboxylase (AADC). Female C57BL/6J mice received 0 or 3mg/kg heptachlor in peanut butter every 3 days for 2 weeks prior to breeding and throughout gestation and lactation until the offspring were weaned on postnatal day (PND) 21. On postnatal day 28, DAT, VMAT2, and TH levels were increased by 100, 70, and 30%, respectively, with no change in AADC levels or total dopamine levels. The ratio of DAT:VMAT2 was increased 29%. Since an increase in the DAT:VMAT2 ratio appears to predict susceptibility of brain regions to Parkinson's disease (PD) and results in increased toxicity of MPTP, these results suggest that alterations of the dopaminergic system by developmental heptachlor exposure may increase the susceptibility of dopamine neurons to toxic insult.
Caudle
W Michael
WM
Center for Neurodegenerative Disease, Emory University, Whitehead Biomedical Research Building 505, 615 Michael Street, Atlanta, GA 30322, USA.|Department of Environmental and Occupational Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
Richardson
Jason R
JR
Center for Neurodegenerative Disease, Emory University, Whitehead Biomedical Research Building 505, 615 Michael Street, Atlanta, GA 30322, USA.|Department of Environmental and Occupational Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
Wang
Minzheng
M
Center for Neurodegenerative Disease, Emory University, Whitehead Biomedical Research Building 505, 615 Michael Street, Atlanta, GA 30322, USA.|Department of Environmental and Occupational Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
Miller
Gary W
GW
Center for Neurodegenerative Disease, Emory University, Whitehead Biomedical Research Building 505, 615 Michael Street, Atlanta, GA 30322, USA.|Department of Environmental and Occupational Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
D000818:Animals; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism; D004563:Electrochemistry; D005260:Female; D006533:Heptachlor / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008454:Mazindol / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism*; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D007306:Insecticides; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017661:Receptors, Presynaptic; C493453:Slc18a2 protein, mouse; C493215:Slc6a3 protein, mouse; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D006533:Heptachlor; D008454:Mazindol; D004298:Dopamine