[Comparative analysis of electroacupuncture, metformin and their combination on cognitive function and senile plaques of cerebral cortex and hippocampus in APP/PS1 mice].

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) 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: ß-site amyloid precursor protein cleaving enzyme 1(ßACE1) 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 ßACE1 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 ßACE1 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 ßACE1 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 ßACE1 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.

[Effect of electroacupuncture on the expression of insulin signal pathway related proteins in hippocampus in mice with Alzheimer's disease].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression of insulin phosphatidylinositol-3 kinase/glycogen synthetase kinase-3α (PI3K/GSK3α) signal pathway related proteins in the hippocampus in mice with Alzheimer's disease (AD), and to explore the regulatory mechanism of EA on improving the pathological characteristics of AD. METHODS: Twelve male APP/PS1 double transgenic mice were randomly divided a model group and a treatment group, 6 mice in each group; another 6 wild-type male mice were taken as the control group. The mice in the treatment group were treated with EA (continuous wave, 2 Hz of frequency) at "Baihui" (GV 20) and bilateral "Shenshu" (BL 23), once a day; 7-day treatment was taken as a course of treatment, and 2 courses of treatment were given. The immunohistochemistry method and Western blot method were used to detect the distribution and expression level of hippocampal PI3K/GSK3α signal pathway related proteins P85α, P110α, GSK3α and pS21GSK3α, and the number of hippocampal senile plaques (SP) was observed. RESULTS: The proteins of P85α, P110α, GSK3α and pS21GSK3α were mainly distributed in the cytoplasm of hippocampal neurons, and the GSK3α was also distributed in the axons of neurons in the model group and the treatment group. The immunohistochemistry results showed that the distribution level of GSK3α in the hippocampus in the model group was significantly higher than that in the control group (P<0.001), and the distribution level of pS21GSK3α, P85α and P110α was significantly decreased (P<0.01, P<0.001); compared with the model group, the distribution level of GSK3α in the hippocampus in the treatment group was significantly decreased (P<0.001), and the distribution level of pS21GSK3α, P85α and P110α in hippocampus was significantly increased (P<0.05, P<0.001). The Western blot results showed compared with the control group, the expression of pS21GSK3α, P85α and P110α as well as the ratio of pS21GSK3α/GSK3α in the hippocampus in the model group were significantly decreased (P<0.001), and the expression of GSK3α was increased (P<0.05); compared with the model group, the expression of pS21GSK3α, P85α, P110α and the ratio of pS21GSK3α/GSK3α in the hippocampus in the treatment group were significantly increased (P<0.01, P<0.001), and the expression of GSK3α was decreased (P<0.05). Compared with the control group, the number of hippocampal SP in the model group was significantly increased (P<0.001); compared with the model group, the number of hippocampal SP in the treatment group was significantly decreased (P<0.01). CONCLUSION: EA could effectively regulate the expression of PI3K/GSK3α signal pathway related proteins in the hippocampus in mice with AD, so as to reduce the formation and deposition of SP.