Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system

Numerous epidemiological studies have shown an association between pesticide exposure and an increased risk of developing Parkinson's disease (PD). Here, we provide evidence that the insecticide dieldrin causes specific oxidative damage in the nigrostriatal dopamine (DA) system. We report that exposure of mice to low levels of dieldrin for 30 days resulted in alterations in dopamine-handling as evidenced by a decrease in dopamine metabolite, DOPAC (31.7% decrease) and HVA (29.2% decrease) and significantly cysteinyl-catechol levels in the striatum. Furthermore, dieldrin resulted in a 53% decrease in total glutathione, an increase in the redox potential of glutathione, and a 90% increase in protein carbonyls, alpha-Synuclein protein expression was also significantly increased in the striatum (25% increase). Finally, dieldrin caused a significant decrease in striatal expression of the dopamine transporter was measured by H-3-WIN 35,428 binding and H-3-dopamine uptake. These alterations occured in the abscence of dopamine nueron loss in the substantia nigra pars compacta. These effects represent the ability of low doses of dieldrin to increase the vulnerability of nigrostiatal dopamine neurons by inducing oxidative stress and suggest that pesticide exposure may act as a promoter of PD. (c) 2007 Elsevier Inc. All rights reserved.