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

Abstract

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 8weeks. 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 20mg/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.

FIGURE 1

Effect of drug treatments on neuronal cell counts of the substantia nigra pars compacta. Animals were sacrificed 1 week after the last treatment. (A) Total number of TH+ neurons per substantia nigra (bilateral). (B) Total number of TH− neurons per substantia nigra (bilateral). (C) Total neuron counts (TH+ and TH−) per substantia nigra (bilateral). Data are represented as group mean ± SEM. *p<0.005, **p<0.001 vs. respective control, ^#p<0.05 vs. saline + paraquat and maneb treatment; one-way ANOVA followed by Bonferroni post-hoc analysis). (D) Low power photomicrographs of representative sections showing PQ and MB-induced loss of TH+ neurons. Low power (4×) photomicrograph of the substantia nigra pars compacta (SNpc) stained for TH-IR and counterstained with cresyl violet acetate (Nissl) in representative tissue sections from mice pretreated with Saline, Caffeine (5 mg/kg) or Caffeine (20 mg/kg) and treated with Saline + Saline or PQ + MB. Typical delineations for stereological counting are shown for the SNpc and ventral tegmental area (VTA).