[Kidney-reinforcing and Governor Vessel-regulating EA Intervention May Improve Learningmemory 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 (=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 learning-memory 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 (<0.01, <0.05), and the platform crossing time of spatial probing test significantly decreased (<0.01) in the model group compared with the control group. After EA intervention, the escape latency on the 5 day of training, and the path length on the 4 and 5 day of training in both EA-2-week and EA-3-week groups were significantly shorter relevant to the model group (<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 (<0.05, <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 (<0.01), and that of the EA-3-week group was considerably increased compared with the EA-2-week group (<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 (<0.01), and was markedly reduced in both EA-2-week and EA-3-week groups (<0.01), and that of the EA-3-week group was significantly decreased compared with the EA-2-week group (<0.01). The expression levels of hippocampal APP and BACE 1 proteins were significantly higher in the model group than in the control group (<0.01), and that of hippocampal IDE was markedly lower in the model group than in the control group (<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 (<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 (<0.01, <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.