Issn Print: 0955-8810
Publication Date: 2006/09/01
P4 TEMPORAL INFLAMMATORY EVENTS IN PARAQUAT/MANEB INDUCED NEURONAL TOXICITY
J. Drouin-Ouellet; M. Lafontaine-Lacasse; M. Saint-Pierre; R.E. Gross; F. Cicchetti
+ Author Information
Author Information: Centre de Recherche en Neurosciences, CHUL, RC-9800, 2705, Boulevard Laurier, Québec, QC, G1 V 4G2
Excerpt
In support of the evidence for the role of environmental toxins in the etiology of Parkinson's disease (PD), we recently demonstrated that the herbicide paraquat (PQ) and the fungicide maneb (MB) are toxic to dopaminergic (DA) neurons in young adult rats (2 months of age). The DA neuronal degeneration was accompanied by significant microglial activation and did not induce peripheral toxicity after a regimen of 8 injections of PQ/MB (2 times a week). However, after only two injections of PQ/MB, ≈50% of older rats (6 months of age) were affected by lung toxicity, but the toxins did not target the brain. The remaining 50% of rats showed increased brain susceptibility to these compounds, consistent with the age-related prevalence of the disease. A strong inflammatory response was also found concurrent with DA neuronal dysfunction, as assessed by Golgi expression, and preceded definite and irreversible neuronal degeneration. With significant peripheral toxicity hampering the study in older rats, we turned to young adult mice to investigate the temporal inflammatory events observable before, during and after DA neuronal degeneration. In young mice (2 months of age), there were no apparent detrimental effects, after two injections of the toxins either to the peripheral or central nervous system. On the third injection, ≈50% of animals suffered from important lung damage, as observed in older rats. The remaining animals were sacrificed at various time points (1 h, 3 h, 7 h, 12 h and 24 h) after a fifth injection of PQ/MB and are currently undergoing post-mortem analyses for DA cell loss and various inflammatory markers such as activated microglia (Iba-1) and macrophages (ED-1) as well as mRNA levels for cytokines and prostaglandins (TNFα, IL-1β, IL-6 and Cox-2). With a definite time course of inflammation, these results should shed light on the true contribution of inflammation as well as the exact inflammatory molecules involved in PQ/MB-induced neuronal toxicity.
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