Abstract: Objective To investigate the effect of estrogen(E2) on different age rat groups of Parkinson’s disease(PD) models induced by Rotenone and its mechanism. Methods 24-month-old SD rats(high age group)and 12-week-age SD rats(low age group)were divided into control group (saline), Rotenone treatment group(Rotenone 2mg/kg), Estrogen treatment group(Rotenone 2mg/kg and E2 1mg/kg)and Tamoxifen treatment group(Rotenone 2mg/kg, E2 1mg/kg and Tamoxifen 1mg/kg). Behavior tests were carried out to observe the change of movement function, Immunohistochemistry and Western blot were used to assess the changes of TH and LC-3.HPLC-ECD was used to detect possible changes of monoamine neurotransmitters in striatum. Results (1)Rotenone reduced significantly high age rat’s rotarod latencies, and prolonged the climbing pole time(P<0.05). E2 ameliorated this effect, Tamoxifen could reduce the effect of E2. (2)Rotenone significantly reduced the number of TH positive cells in high age rats(P<0.05) , E2 could partly restore TH positive cell loss, and Tamoxifen could reduce this effect of E2, so did the expression of TH protein. (3)Rotenone increased the expression of LC-3(P<0.05), E2 did not affect the expression of LC-3, so did Tamoxifen. (4)Rotenone significantly decreased the level of DA and its metabolite DOPAC(P<0.05), elevated the level of 5-HT,especially in high rats(P<0.05). E2 downregulated the influence, and Tamoxifen could reduce the effect of E2. (5)Rotenone increased the number of autophagosomes, but E2 increased the proportion of autolysosomes/autophagosomes. Conclusions High age rat PD model was more reliable. Estrogen promoted autophagy mature, and had obvious therapeutic effect on rat PD model induced by rotenone.

Key words: estrogen, Parkinson's disease, age, autophagy