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Insecticide Exposure in Parkinsonism
Final rept. 1 Jan 1999-31 Dec 2005
VIRGINIA POLYTECHNIC INST AND STATE UNIV BLACKSBURG
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To study the etiology of Parkinsons disease as it may relate to Gulf War Syndrnme the insecticides chlorpyrifos CPF andor permethrin PM were given 3 times over a two week period with or without a single dose of the Parkinsonian neurotoxin MPTP. Biomarkers were then analyzed at t 1,14 and 28 days post-treatment. Potent up-regulation of dopamine transport biomarkers was observed with PM but not CPF at t 1 day. Both insecticides reversibly altered the expression of nicotinic and muscarinic cholinergic receptors at high doses with greater overall effects in the striatum compared to cortex. High doses of both insecticides also increased the toxicity of MPTP at t 28 days post-treatment. Immunocytochemical analysis showed increased glial fibrillary acidic protein GFAP after MPTP or PM treatment but not a significantly enhanced effect when applied together Ti day. Measurements of behavior at t 1 day showed reduced locomotion at high doses of PM and CPF as well as a trend for decreased movement in combined toxicant treatment groups as well t 28 days. Taken together these results suggest that insecticide exposure at high doses may exacerbate idiopathic disease processes. Isomer studies showed that both the cis and trans isomers of PM contribute to the increase in expression of 0-synuclein. Finally 3 and 6 month weekly injections with low doses of PM found little or no toxic effect with or without MPTP. Overall these results suggest little Parkinsonian hazard from the proper use of these insecticides.
APPROVED FOR PUBLIC RELEASE