The Effect Of Electroacupuncture At The Baihui And Shenting Acupoints On Microglia Polarization Of Hippocampus And Learning And Memory In Ad Model Mice

Objective:To investigate whether electroacupuncture at Baihui and Shenting acupoints could alleviate/delay the aggregation of A? deposition and improve the learning and memory function by regulating the polarization of microglia to exert neuro-immune modulation based on the amyloid cascade hypothesis,in the early stage of AD pathology.Methods:Twenty-four APP/PS1 double transgenic mice of 4 months old were divided into 3 groups according to random number table,model group,electroacupuncture(EA)group and nonacupoint group,8 rats in each group;8 wild-type mice in the same nest were taken as Wild group.EA group: Acupoints take Baihui,Shenting two points,voltage 2 V,sparse wave,frequency 1/20 Hz,once every other day,3 times a week,30 min each time,a total of 16 weeks of intervention.Non-acupoint group: Take the non-acupoint points under the bilateral flank,the acupuncture time and course of treatment are the same as those of the EA group.Wild and model mice were harvested under the same conditions without any treatment.The water maze and new object recognition experiments were used to observe the learning and memory ability of each group before and after intervention.The functional magnetic resonance imaging(fMRI)and regional homogeneity(ReHo)analysis methods were used to observe the mice.Changes in brain neuronal activity in each group of mice;immunofluorescence was used to observe the distribution of A? in brain regions and the polarization state of microglia.Results:1.The effect of electroacupuncture to improve learning and memory of APP/PS1 mice: Morris water maze test showed that the average escape latency of model group,EA group and non-acupoint group were significantly longer than that of wild-type group before intervention,while the average number of escape platforms was significantly decreased(P<0.001),and there was no significant difference among three groups(P>0.05);However,the average escape latency of EA group was significantly shortened(P<0.01)than that of model group after intervention,and the average number of times crossing the platform increased(P<0.001).New object recognition test showed that there was no significant difference in the ability of object recognition among the four groups before intervention.After intervention,compared with the wild-type group,the new object recognition index of the model group mice decreased significantly(P<0.05),while the new object recognition index of the EA group mice increased significantly compared with the model group(P<0.05).2.The effect of electroacupuncture on neurological activity in APP/PS1 mice:ReHo analysis revealed that before intervention,the ReHo values of the lefthippocampus and right basal forebrain in the model group were lower than those in the wild-type group(P<0.001).There was no significant difference among the model group,the electroacupuncture group and the non-acupoint group.After intervention,the ReHo values in the bilateral hippocampus of the model group were lower than those in the wild-type group(P<0.001).Compared with the model group,the ReHo values of the motor cortex and hippocampus were increased in the electroacupuncture group(P<0.001).Further Correlation analysis between ReHo value,learning and memory behavior revealed that The number of times of platform crossing in model group and electro-acupuncture group was positively correlated with the ReHo value of hippocampus,and the correlation coefficient was0.633(P<0.001).Further Correlation analysis between ReHo value,learning and memory behavior revealed that the correlation coefficient was 0.833(P=0.011).3.The effect of electroacupuncture reduces A? plaques in hippocampus of APP/PS1 mice: 6E10 immunofluorescence showed that the number of A? plaques in the electroacupuncture group was significantly lower than that in the model group(P<0.01).There was no A? plaques was seen in the hippocampus of the wild-type group mice.4.The effect of electroacupuncture increase expression of M2 microglia in hippocampus of APP/PS1 mice: immunofluorescence results showed that the expression of M2 microglia(CD206,Arg-1)in the model group were significantly lower than those in the wild-type group.(P<0.01).The expression of M2 microglia(Arg-1)in the electroacupuncture group was significantly higher than that in the model group(P<0.05).Conclusions:The early intervention of electroacupuncture Baihui and Shenting acupoints for 16 weeks improved the learning and memory in AD mice,which may be related to the reduction of A? deposition by motivating M2 microglia in the hippocampus.