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 / 针刺研究

ABSTRACT

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 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 (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 5th day of training, and the path length on the 4th and 5th 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.