NEUROTOXIC EFFECTS OF CHLORPYRIFOS EXPOSURE ON NEONATAL MICE

Chlorpyrifos (CPF) is one of the most used organophosphorus insecticide (OP) and putative developmental neurotoxicant in different organisms and also in humans.1,2 Maternal exposure to CPF was found to be dose-related to slower brain growth and associated to several structural abnormalities such as thinning of cerebral cortex.3 In mice, prenatal CPF exposure has the potential to affect long-term brain cognitive function, but the mechanisms are still unknown.3 It has been demonstrated that even sub-lethal doses of neurotoxic pesticides affect behaviour by inhibiting acetylcholinesterase (AChE). To elucidate through what mechanism CPF induces alterations in neurogenesis, we used the M u s m u s c u l u s as animal model. F2 offspring (3-8 month) of Mus musculus females, treated with 3 doses of CPF (0.1-1-10 mg/kg/d) during pregnancy, were used to study the effects of chronic exposure to this compound. The analysis was performed on 84 genes associated to Parkinson disease, using RT2 Profiler PCR Arrays. There was a statistically significant dose-dependent correlation between increasing CPF concentration and the down-regulation for many genes studied at 3 and 8 month mice. It was interesting to note that, among the genes significantly down-regulated, there were those more directly related to Parkinson’s disease, such as the Park2, Sv2b, Gabbr2, Sept5, Atxn2, whereas the expression of the Ubiquitin C, Rgs4 and Chgb showed an up-regulation in 8 month mice. Furthermore, we found alteration of the AChE activity, that was inhibited by the exposure to CPF. The results of our study confirm that CPF can elicit alterations in the gene expression profile during neurogenesis and reinforce the view that the critical window of vulnerability of the developing brain to CPF extends from gestational exposure through postnatal period.4