Insecticide Exposure in Parkinsonism
Annual rept. 1 Jan-31 Dec 2002
VIRGINIA POLYTECHNIC INST AND STATE UNIV BLACKSBURG
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Behavioral, neurochemical, and immunocytochemical studies are characterizing the possible role of insecticide exposure in the etiology of Parkinsons disease as it may relate to Gulf War Syndrome. Chlorpyrifos CP andor permethrin PM were given 3 times over a two week period by injection CP subcutaneous and PM intraperitoneal, with or without a single dose of the Parkinsonian neurotoxin, MPTP 20-30 mgkg, intraperitoneal. PM upregulates dopamine transporter DAT expression with a 28 day time course and at doses as low as 0.2 mgkg, while CP has little effect. Data from western blots of DAT protein correlate well with measurements of 3Hgbrl2935 binding, a ligand for the DAT. When applied as CP PM MPTP, expression of the DAT is significantly decreased, which is consistent with neuronal injury. In addition, this is probably a synergistic interaction, since MPTP and CP are inactive alone, and PM upregulates the DAT. Similar experiments using labeled quinuclidinyl benzilate as a ligand for muscarinic cholinoceptors observed no significant interaction, suggesting that there is a lack of a significant synergistic effect of these compounds on striatal cholinergic pathways. Because technical permethrin is a mixture of four stereoisomers, further work is underway to characterize the isomers of permethrin involved in DAT upregulation.
- Agricultural Chemistry
- Medicine and Medical Research