2012-04-092012-04-092011-12-29MARTINS FILHO, Arnaldo Jorge. Modelo in vitro de parkinsonismo experimental induzido por rotenona: investigação de mecanismos de ação, neuroproteção e morte celular. 2011. xii, 130 f. Tese (Doutorado) - Universidade Federal do Pará, Instituto de Ciências Biológicas, Belém, 2011. Programa de Pós-Graduação em Neurociências e Biologia Celular.https://repositorio.ufpa.br/handle/2011/2600Increasing 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.porAcesso AbertoRotenonaDoença de ParkinsonDoenças neurodegenerativasRato como animal de laboratórioNeurotoxidadeTeseCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA::TOXICOLOGIA