Effect Of Dendrobium Nobile Lindl Alkaloids On Aromatase And Estrogen/ERK Signaling Pathway In APP/PS1 Mice

Objective:To observe the effect of Dendrobium nobile Lindl alkaloids?DNLA?on the learning and memory function of APP/PS1 mice,and explore whether its mechanism is related to aromatase,estrogen and ERK signaling.Methods:This experiment uses female and male APP/PS1 model mice as experimental subjects,seven-month-old APP/PS1 mice were randomly divided into 3 groups?n=10 per group?:APP/PS1 group,APP/PS1+DNLA 10 mg/kg group,APP/PS1+DNLA 20 mg/kg group;wild type?WT?group:a total of 20,half male and female?n=10 per group?.APP/PS1transgenic mice were administered once a day with stomach for 4 months,and WT groups were given the same volume of vehicle?1%double distilled water containing Tween 80?.Before the end of their lives,nesting experiments were used to test the daily activities and instinctual social behavior of mice;Y maze was used to test the learning and memory abilities of mice.thioflavine S staining was used to observe the middle-aged and old age of the mouse cortex;Western blot was used to detect aromatase and estrogen in female and male mouse cortex related protein expression,ERK/pERK protein expression;ADAM10,APP,A?_1-42 protein levels in the non-amyloid pathway of A?;estradiol?E2?in the serum was detected by ELISA.Results:Compared with WT mice,the APP/PS1 transgenic model mice had significantly reduced motor function and learning and memory abilities;the number of senile plaques in female and male female and male APP/PS1 transgenic mice significantly increased;the protein expression of aromatase was significantly reduced at 11 months of age in APP/PS1transgenic mice,and the protein expression of aromatase was significantly higher in male WT mice than in females?P<0.05?.In addition,ADAM10 protein levels were significantly reduced,APP and A?_1-42 protein levels were significantly increased in female and male APP/PS1 mice,and aromatase,ER1,ER2,GPR30 protein levels were significantly reduced,and pERK protein levels were significantly increased;in females of APP/PS1 mice,the level of serum estrogen significantly decreased,while the level of serum estrogen did not change significantly in male.After administration of DNLA,Compared with APP/PS transgenic mice,female APP/PS1 transgenic mice nesting ability was significantly increased;female and male APP/PS1 mice spatial learning and memory ability was significantly improved;the number of senile plaques in female and male APP/PS1 transgenic mice were significantly reduced after administration;the levels of ADAM10 protein in female and male APP/PS1mice were significantly increased,the levels of APP and A?_1-42 proteins were significantly reduced,the levels of aromatase,ER1,ER2,GPR30 proteins were significantly increased,and the levels of pERK protein were significantly reduced;The content of E2 in serum increased significantly.Conclusion:?1?Under the experimental conditions,the expression of aromatase has a significant gender difference under physiological conditions.The gender difference disappears in the brain of APP/PS1 mice,and its expressions in female and male APP/PS1mice are significantly reduced;?2?DNLA may improve the learning and memory of APP/PS1 mice by up-regulating aromatase and estrogen receptors as well as down-regulating pERK.