Action Of Dopamine Metablisom In Rotenone Toxicity In Dopamine Neurons

Parkinson's disease (PD) is a late-onset and progressive motor disease marked by relatively selective nigrostriatal dopaminergic degeneration. The pathogenesis of PD is not completely understood but environmental and genetics factors are believed to play important roles. Environmental factors such as MPTP exposure have long been suggested to be associated with neurodeneration, especially in Parkionson's disease. Further, Parkinsonism was elicited in animals treated with rotenone. Studies suggest involvement of pesticide exposures in sporadic PD. Rotenone, a widely used pesticide, is believed to be associated with PD. However, the mechanism of rotenone in PD is unclear. Thus, studies in the mechanism of rotenone-inducing-PD in molecular level is helpful for understanding PD.In recent years, association between endogenous dopamine toxicity and PD has become the focus. Dopamine is synthesized and oxidized in cytoplasm. The oxidation of dopamine can produce multiple oxygen free radicals, which are toxic to dopamine neurons. In physiological conditions, dopamine is stored in synaptic vesicals, thus to avoid dopamine autoxidation and toxicology. In rotenone model of PD, we hypothesis, the natural balance of dopamine and oxidation may be destroyed and dopamine metabolism dysfunction maybe play a role in rotenone model of PD with selective nigrostriatal system degeneration. Therefore, we carried out some researches in this area, to further investigate the mechanism of rotenone model of PD and to explore the action of dopamine metabolism dysfunction in endogenous dopamine toxicity in PD.Method: 1. A vitro studies: PC12 cells were intoxicated with rotenone: Cell morphogy and ultramicrostructure were observed. Oxidative stress was assayed with biochemical method. Protein and mRNA expression of TH, DAT and VMAT2 were detected with immunohistochemistry, Westernbot and RT-PCR respectively. Kinetic [Ca2+]i was monitored with Ca2+ Imaging and Analysis System. Synaptic vesicals of PC12 were labelled with FMI-43 and were observed with CLMS. Medicine intervention on rotenone...