Abstract: Behavioral, neurochemical, and immunocytochemical studies characterized the possible role of insecticide exposure in the etiology of Parkinson's disease as it may relate to Gulf War Syndrome. Chlorpyrifos (CP) and 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 (10-30 mg/kg, intraperitoneal) . Some synergism was observed at 30, but not 10 mg/kg MPTP with respect to behavior and dopamine depletion. PM (0.8-1.5 mg/kg) increased dopamine transporter protein expression 30%, similar to its ability to increase dopamine uptake and GBR12935 binding at these doses. Time course studies showed that the magnitude of transporter expression increased to roughly double the value of controls 4 weeks after treatment, suggesting a slow process underlies this effect. In immunocytochemical studies, PM at 200 mg/kg, and mixed doses of PM and CPF (200 and 50 mg/kg, respectively) showed no change in tyrosine hydroxylase staining, but did cause an increase in glial fibrillary acidic protein consistent with neuronal injury. Similarly, PM (200 mg/kg) and CPP (75 mg/kg) down regulated both high and low affinity binding sites for the nicotinic receptor ligand, epibatidine. Further work is underway to characterize this down regulation.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual rept. 1 Jan 2000-31 Dec 2001 |
| Pages: |
38 |
| Report Date: |
JAN 2002 |
| Contract Number: |
DAMD17-98-1-8633 |
| Report Number: |
A581604 |
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