Perinatal heptachlor exposure increases expression of presynaptic dopaminergic markers in mouse striatum

• Type of Material: Conference Paper
• Authors: William Caudle, Emory University; Jason R. Richardson, Emory University; Minzheng Wang, Emory University; Gary Miller, Emory University
• Language: English
• Date: 2005-08-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2004 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.neuro.2004.09.003
• Title of Journal or Parent Work: NeuroToxicology
• Conference or Event Name: Twenty-first International Neurotoxicology Conference
• Volume: 26
• Issue: 4 SPEC. ISS.
• Start Page: 721
• End Page: 728
• Grant/Funding Information: This work was supported by NIH U54 ES01268 and R21 ES012315 (GWM) and T32-NS07480 (JRR).
• Keywords: Electrochemistry; Parkinson's disease; Female; Mice; Mice, Inbred C57BL; Heptachlor; Dopamine Uptake Inhibitors; Vesicular monoamine transporter 2; Vesicular Biogenic Amine Transport Proteins; Neostriatum; Receptors, Presynaptic; Insecticides; Dopamine Plasma Membrane Transport Proteins; Blotting, Western; Chromatography, High Pressure Liquid; Mazindol; Membrane Transport Proteins; Membrane Glycoproteins; Dopamine transporter; Developmental neurotoxicity; Tyrosine hydroxylase; Vesicular Monoamine Transport Proteins; Animals; Dopamine; Male; Nerve Tissue Proteins

Abstract

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 3 mg/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.