The effects and mechanism of estrogen on rats with Parkinson's disease in different age groups.
OBJECTIVE
In order to investigate the effect and mechanism of estrogen in rotenone-induced Parkinson's disease (PD) rats in different age groups.


METHODS
we established rat models of PD by rotenone at different interventions. Then, behavioral tests, immunohistochemistry, western blot, high-performance liquid chromatography-electrochemical detector (HPLC-ECD) and electron microscopy were performed.


RESULTS
Results revealed the following: (1) Rotenone significantly reduced rotarod latencies in senile rats, prolonged their climbing pole time, and decreased TH positive cells, DA and its metabolite, DOPAC. Estrogen ameliorated this effect, in which weaker effects were observed in younger rats compared with older rats. (2) Rotenone increased the expression of LC3-II in older rats, but estrogen and tamoxifen did not show the same effect. (3) Rotenone increased the number of autophagosomes, but estrogen increased the proportion of autolysosomes/autophagosomes in the rotenone-treated group. (4) U0126 could reduce the number of autophagosomes in the rotenone-treated group, but this did not change the proportion of autolysosome/autophagosome in combining rotenone with the estrogen group. Rapamycin did not increase the number of autophagosomes in the rotenone-treated group, but combining rapamycin with estrogen and rotenone was able to further increase the proportion of autolysome/autophagosomes. Therefore, we speculate that the senile rat model of PD was more reliable than that in young rats.


CONCLUSIONS
In addition, estrogen could promote autophagy maturation through the ERK pathway, and had an obvious therapeutic effect on the rat model of PD.
Department of Neurology, Jiangsu University Affiliated People's Hospital Jiangsu, China.
Xue-Zhong
XZ
Li
Department of Neurology, Jiangsu University Affiliated People's Hospital Jiangsu, China.
Chen-Yan
CY
Sui
Department of Neurology, Jiangsu University Affiliated People's Hospital Jiangsu, China.
Qiang
Q
Chen
Department of Neurology, Jiangsu University Affiliated People's Hospital Jiangsu, China.
Yuan-Su
YS
Zhuang
Department of Neurology, Jiangsu University Affiliated People's Hospital Jiangsu, China.
Hong
H
Zhang
Department of Neurology, Jiangsu University Affiliated People's Hospital Jiangsu, China.
Xiao-Ping
XP
Zhou
Estrogen; Parkinson’s disease; age; autophagy