Systemic exposure to paraquat and maneb models early Parkinson's disease in young adult rats

In recent years, several lines of evidence have shown an increase in Parkinson's disease (PD) prevalence in rural environments where pesticides are widely used. Paraquat (PQ-herbicide) and maneb (MB-fungicide) are among the compounds suspected to induce neuronal degeneration and motor deficits characteristics of PD. Here, we investigated the effects of PQ and NIB on dopaminergic (DA) neuron-glia cultures and in vivo in young adult rats. In vitro, PQ led to a loss of DA as compared to non-DA neurons and microglial activation in a dose-dependent manner. Addition of NIB had no further effect nor did it lead to microglial activation when used alone. In vivo, 2-month old young adult rats were subjected to intraperitoneal injections of vehicle (n = 4), PQ alone (n = 8), or PQ in combination with NIB (n = 8) twice a week for 4 weeks and were sacrificed the day following the last injection. Significant loss of nigral DA neurons was observed in both treatment groups, but a significant decrease in striatal DA fibers was not found. Microglial activation was seen in the nigra of rats subjected to PQ with or without MB. Behavioral analyses demonstrated a mixed pattern of motor impairments, which may have been related to early effects of nigral DA neuronal loss or systemic effects associated with NIB exposure in addition to PQ. These results indicate that exposure to PQ with or without NIB induces neuro degeneration which might occur via an early inflammatory response in young adult animals. (c) 2005 Elsevier Inc. All rights reserved.