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Functional Neurogenomics of Pyrethroid Exposure and Effects on NeurodegenerationEPA Grant Number: FP916437
Title: Functional Neurogenomics of Pyrethroid Exposure and Effects on Neurodegeneration
Investigators: Guillot, Thomas S.
Institution: Emory University
EPA Project Officer: Manty, Dale
Project Period: January 1, 2004 through December 31, 2006
Project Amount: $111,344
RFA: STAR Graduate Fellowships (2004) RFA Text | Recipients Lists
Research Category: Fellowship - Toxicology , Academic Fellowships , Health Effects
It is imperative to understand the extent to which low-level exposure to insecticides affects the nervous systems of mammals. Because the majority of insecticides are neurotoxicants and the insects targeted for eradication share similar target sites for toxicity as nontarget organisms, there is significant risk for damage to nontarget organisms. Toxicity studies for registration of insecticides are typically high doses designed to detect overt toxicity, such as pathological lesions. More subtle changes in neurochemistry induced by low-level exposure, however, can have a critical impact on normal neurochemical function. The objective of this research is to evaluate the impact of lower doses of insecticides on nontarget organisms to determine the possible neurotoxic effects that may be occurring in the environment.
My hypothesis is that repeated low-level exposure to deltamethrin or permethrin alters dopaminergic neurochemistry and results in increased vulnerability to the dopaminergic neurotoxin MPTP . To test this hypothesis, two specific aims will be pursued. The effects of permethrin and deltamethrin on the dopaminergic system will be determined. This will be accomplished using an integrated approach involving laser-capture microdissection of nigrostriatal dopamine neurons and subsequent microarray analysis, along with neurochemical, immunochemical, and behavioral analyses. Additionally, I will determine whether prior exposure to permethrin or deltamethrin results in increased vulnerability to MPTP, as assessed using neurochemical, immunochemical, and behavioral analyses.