Caffeine protects against combined paraquat and maneb-induced dopaminergic neuron degeneration

Environmental exposures suspected of contributing to the pathophysiology of Parkinson's disease (PD) include potentially neurotoxic pesticides, which have been linked to an increased risk of PD. Conversely, possible protective factors such as the adenosine antagonist caffeine have been linked to a reduced risk of the disease. Here we assessed whether caffeine alters dopaminergic neuron loss induced by exposure to environmentally relevant pesticides (paraquat and maneb) over 8 weeks. The number of nigral neurons positive for tyrosine hydroxylase immunoreactivity (TH+) was assessed using stereological methods and found to be significantly reduced (to 60% of control) by combined pesticide treatment. Caffeine at 20 mg/kg significantly reduced TH+ neuron loss (to 85% of the respective control). The results demonstrate the neuroprotective potential of caffeine in a chronic pesticide exposure model of model of PD.