Increasing evidence has suggested a role for environmental factors, such as
exposure to pesticides, in the pathogenesis of Parkinson’s disease. In experimental animals
the exposure to rotenone, a common herbicide and piscicide, induces features of
parkinsonism by inhibiting the activity of mitochondrial complex I. Here we propose to
investigate rotenone-induced death of neurons by using primary neuron-enriched and
neuron-glia cultures from the rat hippocampus and ventral mesencephalon. The neuronal
loss was evaluated with the colorimetric MTT assay. Our results showed significant
reduction in the cell viability after exposure to rotenone in a dose- but not in a timedependent
manner. We also discovered a remarkable feature of rotenone-induced
degeneration of cultured neurons. The higher susceptibility was observed in neuron-glia
cultures from the ventral mesencephalon, suggesting that the presence of glia, especially
microglia, is an important factor contributing to neurodegeneration. Also, as showed by
immunohistochemistry, this type of culture presented the higher density of tirosinahidroxilase
(TH)-positive neurons. Mechanistically, our results with calcium blockers
showed a minimal role played by external calcium, and an important synergistic influence
of the ions from the internal stores in the rotenone-induced neurodegeneration. Indeed, in
this study, we report that aqueous extract of mahogany leaves didn’t protect against the
rotenone-induced toxicity, in the used concentration; and promoted a synergistic effect
when associated with rotenona. Finally, the mahogany leaves extract induced celular death
both necrosis and apoptosis. The results of this study should advance our understanding of
the mechanism of action for environmental factors in the pathogenesis of Parkinson’s
disease.
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