The Effects Of Electroacupuncture On The Senile Plaques And The Insulin Signal Pathway Related Proteins In The Brain Of APP~+/PS1~+ Double Transgenic Mice

Objective:The occurrence and development of AD are related to the impairment of glucose utilization and energy metabolism in the brain.Moreover,it is further pointed out that the abnormal energy metabolism is closely related to the damage of insulin signaling pathway.The olfactory bulb,hippocampus and cortex as brain regions closely related to the pathogenesis of AD,are the changes of insulin PI3K/GSK3 signaling pathway related proteins consistent in the early stage of AD?Can electroacupuncture interfere with it?Therefore,this study aims to observe the effects of electroacupuncture stimulation on the distribution and expression of related proteins in the signaling pathway PI3K/GSK3a in the olfactory bulb,hippocampus and cortex of APP+/PS1+ double transgenic mice,as well as on SP deposition.Preliminary investigating the effect of electroacupuncture on the pathological process of AD by insulin signal transduction pathway.Methods:Male three month old APP+/PS1+ double transgenic mice were randomly divided into model group and electroacupuncture group,while wild type C57BL/6J mice of the same age was the control group;with 6 mice in each of the above group.Electroacupuncture stimulated Baihui "(GV 20)and bilateral "Shenshu"(BL 23)in the electroacupuncture group,once a day for 7 consecutive days for 1 course of treatment and 2 courses of treatment;ipGTT was used to detect the blood glucose in each group at different time periods;ELISA assay was performed to test serum insulin levels;IHC and WB assays were taken to test and analyze the changes of SP and proteins IRS1,pS616"IRS1,P85a and P110?,GSK3?,pS21-GSK3a on the signaling pathway of PI3K/GSK3a in the olfactory bulb,hippocampus and cortex of the mice in each group.Results:IpGTT and ELISA results showed that the levels of peripheral blood glucose and serum insulin in the model group were significantly increased than the control group;while,peripheral blood glucose and serum insulin levels in the electroacupuncture group were significant decrease than the model group.IHC results showed that SP were detected in the olfactory bulb,hippocampal and cortex of the model group mice and the electroacupuncture group;however,the number of SP in the model group was obviously increased than the control group and the electroacupuncture group.The results of IHC and WB showed that protein levels of IRS1,pS21-GSK3?,and P110? and P85a in the olfactory bulb,hippocampal and cortex of the model group were clearly decreased than the control group,while the protein expression levels of GSK3a and pS616"IRS1 were significantly increased than the control group;however,the expression levels of IRS1,pS21-GSK3a,P110? and P85a in the electroacupuncture group were visibly increased than the model group,and the levels of GSK3? and pS616-IRS1 were distinctly decreased than the model group.Meanwhile,the results of IHC further showed that the above proteins were mainly distributed on the neurons in the olfactory bulb,hippocampus and cortex.Conclusion:EA can regulate abnormal glucose and insulin levels in APP+/P31+double transgenic mice and maintain relatively normal energy metabolism.It can also reduce SP deposition by regulating the proteins expression of IRS1/pS616-IRS1 and the subunits of PI3K(P85a and P110?)in the olfactory bulb,hippocampus and cortex of APP+/PS1+double-transgenic mice,as well as the downstream pS21-GSK3?/GSK3a related proteins.