A Correlation Study Between Gonadotropin Releasing Hormone And Pathogenesis Of Alzheimer's Disease In Mice

Abstract:Ojective:The present study was designed to observe dynamic observation of gonadotropin releasing hormone(GnRH) in the mice brain modling Alzheimer's disease and its correlation with the pathogenesis of AD.Methods: Animals were randomly divided into seven groups:0d,15d,30d,45d,60d,75d and 90d group,each group was divided into control group and AD model group again.AD model mice were made by D-galactose(ip,120mg·kg-1·d-1) and aluminum chloride(ig,10mg·kg-1·d-1).The ability of learning and memory in AD modle mice were studied by step-down test;The level of tau phosphorylation at Thr231 were detected by Western blot. ELISA was used to measure the estrogen level of all the subject. The expression and distribution of GnRH,GnRHR and Aβ40 were observed by immunohistochemistry (GnRHl:100,GnRHRl:100,Aβ40 1:100).Results: (1)Compared with the control group,AD model mice in 45,60,75,90 days showed a significant decrease in study results(P<0.05),and a significant increased in the memory mistake number(P<0.01),and a significant decrease in the latency time(P<0.05);(2)Compared with the control group,the expression of Aβ40 and Tau-pThr231(Hyperphosphorylation of tau at Thr231) increased in 45,60,75 and 90 days(P<0.05);(3)Estrogen level in serum, AD mice in 90 days was obviously lower than the control group(P<0.05).(4)In the level of GnRH in brain,AD mice in 60,75,90 days were significantly decreased compared with the control group(P<0.05).The level of GnRHR was no significant difference.Conclusion:The results suggested that:(1)With the prolonged administration of making model,AD mice showed deficits in learning ability,and the expression of AP40 brain gradually increased in brain,and the expression of Tau-pThr231 tended to increase,and showed positively correlated with Aβ40.Tau-pThr231 can be calibrated AD process in mice.(2)That the level of estradiol in serum and the expression of GnRH in hypothalamic showed a downward trend in AD process,and was related with the pathological changes of AD.The mechanism may be as follows:with the progression of AD, GnRH has reduced, estradiol level was decreased, so that Aβ40 was deposited and Tau-pThr231 was upregulated,thus promoting AD course.