IN VIVO AND IN VITRO EFFECTS OF THE PESTICIDE ATRAZINE ON BASAL GANGLIA FUNCTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Parkinson¿s Disease (PD) is a debilitating neurodegenerative disease of the basal ganglia and has an elusive etiology. Recently, a possible link between PD and pesticide exposure has been suggested. The herbicide atrazine is the most widely used pesticide in the US, with ground water contamination being a major concern. Currently, there are no data addressing atrazine effects on basal ganglia function. This research project explores the hypothesis that short-term exposure to atrazine would result in persistent neurotoxicity with the degree of neurotoxicity being dependent on the age of the subjects. Moreover, it is hypothesized that chronic, low-level exposure to atrazine will not be neurotoxic on its own, but it will potentiate the toxicity of a typical basal ganglia neurotoxicant such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To address this hypothesis, C57BL/6 mice, 1, 3, and 10 months of age, will be exposed to various dosages of atrazine for either short-term (14 days) or long-term (up to 26 weeks) and the degree of dopaminergic neurodegeneration will be assessed after termination of atrazine exposure. Additionally, to gain a mechanistic insight on atrazine-induced basal ganglia neurotoxicity, in vitro experiments with striatal slices and mixed mesencephalic cultures will be performed.