Kidney-reinforcing and Governor Vessel-regulating EA Intervention May Improve Learning-memory Possibly by Suppressing Formation of Senile Plaques in Hippocampus in APP/PS 1 Double Transgenic Alzheimer's Disease Mice

Objective To observe the effect of electroacupuncture(EA)intervention on learning-memory ability and the expression of senile plaques(SP),amyloid precursor protein(APP),β-secretase 1(BACE 1)and insulin degrading enzyme(IDE)in the hippocampus in APP/presenilin 1(PS 1)double transgenic Alzheimer's disease(AD)mice,so as to reveal its mechanisms underlying improvement of AD.Methods A total of 18 male APP/PS 1 double transgenic AD mice were randomly divided into model,EA-2-week and EA-3-week groups(n=6 in each).The control group was consisted of 6 male wild mice.EA(2 Hz,2 mA)was applied to"Baihui"(GV 20)and bilateral"Shenshu"(BL 23)for 15 min,once a day,with 7 days being a therapeutic course,2 or 3 courses altogether and with an one day's interval between every two courses.The spatial learningmemory ability was assessed using Morris water maze test during 5 days' training.The immunoactivity of SP in the hippocampus tissue was detected by immunohistochemistry,and the expression levels of APP,BACE 1 and IDE in the hippocampus were analyzed by Western blot.Results Following modeling,the escape latency and path length of hidden platform tests were significantly increased(P<0.01,P<0.05),and the platform crossing time of spatial probing test significantly decreased(P<0.01)in the model group compared with the control group.After EA intervention,the escape latency on the 5 th day of training,and the path length on the 4 th and 5 th day of training in both EA-2-week and EA-3-week groups were significantly shorter relevant to the model group(P<0.01),and those of the EA-3-week group were considerably shorter than those of the EA-2-week group in the escape latency and path length(P<0.05,P<0.01).The platform crossing times of spatial probing test were significanthy increased in both EA-2-week and EA-3-week groups in comparison with the model group(P<0.01),and that of the EA-3-week group was considerably increased compared with the EA-2-week group(P<0.05).Immunohistochemical staining showed that the number of SP in the hippocampus was markedly increased in the model group compared with the control group(P<0.01),and was markedly reduced in both EA-2-week and EA-3-week groups(P<0.01),and that of the EA-3-week group was significantly decreased compared with the EA-2-week group(P<0.01).The expression levels of hippocampal APP and BACE 1 proteins were significantly higher in the model group than in the control group(P<0.01),and that of hippocampal IDE was markedly lower in the model group than in the control group(P<0.01).After EA,the increased expression levels of APP and BACE 1 proteins and the decreased expression level of IDE in the EA-2-week and EA-3-week groups were significantly inhibited(P<0.01).The effects of EA-3-week were significantly stronger than those of EA-2-week in down-regulating the expression of APP and BACE 1 proteins and up-regulating the expression of IDE(P<0.01,P<0.05).Conclusion EA stimulation of GV 20 and BL 23 can improve the learning-memory ability in APP/PS 1 double transgenic AD mice,which may be related to its effects in down-regulating the expression of SP,APP and BACE 1 proteins and up-regulating the expression of IDE protein in the hippocampus.