The Effect Of Liquirtigenin On Ovariectomized APP/PS1 Double Transgenic Mice

ObjectiveIn this study,we established the postmenopausal(ovariectomized)model of APP / PS1 double transgenic mice.(1)To investigate the effects of different time points after bilateral ovariectomy on cognitive memory and autophagy in Alzheimer 's disease(AD)model mice.(2)To investigate the effect of Liquirtigenin on cognition and autophagy in APP / PS1 double transgenic mice after ovariectomy for 1 week,and to provide new clues for the treatment of AD patients with postmenopausal women.Methods1,the first part: the establishment of stable and reliable mouse menopause(bilateral ovariectomy,OVX)model: 3-month-old female APP / PS1 double transgenic mice were ovariectomized and sham operation,age matched C57 mice is normal control.The levels of A?40 and A?42 were detected by ELISA and the expression of Beclin1,LC3,and P62 were detected by Western blot.2,the second part: To investigate the effect of Liquirtigenin(LG)on APP / PS1 double transgenic mice after ovariectomy for 1 week:(1)3-month-old female APP / PS1 double transgenic mice were randomly divided into the following four groups: sham operation + control group(sham),ovariectomized + reagent control group(OVX),ovariectomized + Liquirtigenin(OVX + LG)and ovariectomized + estradiol(E2)group(OVX + E2);(2)After 1 week of model establishment,each group was given the corresponding reagent or drug treatment;(3)Morris water maze test was to detect the spatial learning and memory of each group mice;(4)weighing uterine weight;(5)immunohistochemistry and Thioflavin S staining to detect senile plaque deposition in mice;(6)The levels of A?40 and A?42 were detected by ELISA;(7)The expression of ER?,ER?,Beclin1,Lc3 and P62 protein was detected by western blot.ResultsThe first part: There was no significant difference in the spatial learning ability of AD mice at 1 week after ovariectomy.After 1 month and 3 months of ovariectomy,the spatial learning and memory abilities of mice were decreased.ovariectomy causes uterus atrophy and weight reduction.There was no significant change in senile plaques and A? in the brain of APP / PS1 double transgenic mice ovariectomy after 1 week.After surgery for 1month and 3months,the number of senile plaques and plaque area were higher than those in sham operation group,and there was no significant change in A?40,significantly increased in A?40.The level of autophagy-related protein was detected by WB.The level of beclin1 was decreased with the prolongation of operation time.LC3 was increased in one week after operation,and decreased in 1 month and 3 months after operation.P62 was no significant change in ovariectomized after 1 week,it become an upward trend after 1month and 3 months.The second part: after 3 months of treatment of Liquirtigenin,Morris water maze experiment showed that the ability of spatial learning and memory in the treatment group was increased;the effect of Liquirtigenin on the uterus was not statistically different,E2 treatment increased uterus weight;Liquirtigenin and E2 treatment can make senile plaques,A? decrease,and no significant difference between the two groups;Liquirtigenin treatment increased ER? protein level significantly,and E2 treatment can significantly upregulate ER?,ER?;Liquirtigenin and E2 treatment can improve Beclin1,LC3 protein levels,and decreased P62 levels.Conclusion1 Ovariectomy decrease spatial learning and memory of AD mice,increase senile plaques and A? deposition with the time of sex hormone deficiency,and these changes may be related to autophagy;2 Liquirtigenin treatment could improve the spatial learning and memory of ovariectomized APP / PS1 double transgenic mice;3 The effect of Liquirtigenin on uterus of ovariectomized APP / PS1 double transgenic mice was lower than that of E2,indicating that the side effects of Liquirtigenin on the uterus were less;4 Liquirtigenin treatment could reduce the senile plaque deposition,which may be associated with it upregulating ER? and regulating of autophagy.