Objective To compare the effect of electroacupuncture(EA)

metformin and EA plus metformin on the cognitive ability and senile plaques(SPs) in cerebral cortex and hippocampus of Alzheimer's disease(AD) mice

so as to explore a better treatment method for AD. Methods Twenty-four male APP/PS1 mice were randomly divided into model

metformin(medication)

EA and EA+medication groups

with 6 mice in each group. Other 6 male wild C57 mice were used as the control group. EA(2 Hz

1.0 mA) was applied to “Baihui”(GV20) and “Shenshu”(BL23) for 15 min

once a day

for 4 weeks

with 1 day's off every week. The mice of the medication group received gavage of metformin(300 mg·kg

(-1)

·d(-1)·d

(-1)

) once a day for 4 weeks. Morris water maze tests were used to assess the cognitive function of mice. H.E. staining was used to observe the histopathological changes of neurons in the cortex and hippocampus. Immunohistochemical method was used to observe the cerebral cortex and hippocampal SPs. The expression levels of SPs formation-related proteins: β-site amyloid precursor protein cleaving enzyme 1(βACE1) and insulin-degrading enzyme(IDE) in the cortex and hippocampus were detected by Western blot.Results Compared with the control group

the escape latency

number of SPs and the expression of βACE1 in the cortex and hippocampus were ob-viously increased(P

<

0.01)

and the times of platform quadrant crossing and the expression of IDE protein were markedly decreased in the model group(P

<

0.01). In comparison with the model group

the escape latency

and the number of SPs and expression of βACE1 proteins in the cortex and hippocampus in the 3 treatment groups were significantly down-regulated(P

<

0.01)

while the times of platform quadrant crossing

and the expression of IDE protein in both cortex and hippocampus of the three treatment groups were considerably up-regulated(P

<

0.01). Comparison among the three treatment groups showed that the therapeutic effect of EA+medication was significantly superior to that of medication and simple EA in down-regulating the escape latency

the number of SPs and expression of βACE1 in the cortex and hippocampus(P

<

0.01)

and in up-regulating the times of the platform quadrant crossing

and expression of IDE protein in both cortex and hippocampus(P

<

0.01). No significant differences were found between the simple medication and simple EA in all the indexes mentioned above(P

>

0.05).Conclusion EA

metformin and EA plus metformin can improve cognitive ability and relieve SP formation in cerebral cortex and hippocampus in AD mice

which may be associated with their functions in down-regulating the expression of βACE1 and up-regulating the expression of IDE. The therapeutic effects of EA plus metformin are apparently better than those of simple EA and simple metformin.