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.