A Study Of Effects Of Rotenone On The Pathogenesis Of Parkinson's Disease Rat

Objective: To investigate the underlying mechanism on rotenone rat model of Parkinson's disease( PD). Whether it may be due to the changes of proteasomal activity, endoplasmic reticulum stress, or whether glyceraldehydes-3-phosphate dehydrogenase (GAPDH) played a role within it?Methods: Rotenone was used to produce a rat model with PD. The proteasomal activity in substantial nigra and in hippocampus within the experimental rat (experimental group) as well as within the normal rats (control group) were measured by detecting the fluorescence units given out by the reactant of proteasome with its 3 substrates tagged with fluorescence. Immunohistochemical assay was utilized to observe whether the nuclear translocation of GAPDH exists in both substantial nigra neurons and hippocampus neurons, and RT-PCR was used to detect the expression of xbp1, which is caused by endoplasmic reticulum stress.Results: 1. Compared with the control group, the postacidic-like hydrolysing activity decreased significantly (p<0.05) in substantia nigra of the experimental group, while chymotrypsin-like and trypsin-like hydrolysing activity decreased even more significantly (p<0.01) in substantia nigra of the experimental group. The postacidic-like hydrolysing activity kept unchanged, while the rest two decreased significantly in the hippocampus (p<0.01). Furthermore, the decrease of chymotrypsin-like,trypsin-like hydrolysing activity in substantia nigra was more significant than that in hippocampus (p<0.01). 2. The nuclear translocation of the GAPDH was not observed in this experiment in the rotenone rat model with PD. 3. Rotenone may promote the expression of xbp1 in the PD rat model.Conclusions: 1. Rotenone can impair the proteasomal function in both substantia nigra and hippocampus, with that more severely impaired in substantia nigra. 2. Rotenone may be able to strengthen the effects of endoplasmic reticulum stress in both substantia nigra and hippocampus. 3. There was no evidence showed the existence of the nuclear translocation of the GAPDH in the pathogenesis of the rotenone rat model of PD by this experiment.