RESUMO
OBJECTIVE: To investigate the effect of electroacupuncture (EA) at "Baihui "(GV20) and "Shenshu "(BL23) on activation of glial cells, expression of inflammatory factor proteins and aquaporin 4 (AQP4)in the hippocampus of amyloid precursor protein/presenilin-1 (APP/PS1) transgenic mice, so as to explore its mechanisms underlying improvement of Alzheimer's disease(AD). METHODS: Twenty C57/BL6 background male APP695/PS1-dE9(APP/PS1) double transgenic mice (model group) and 20 wild type (WT) C57/BL6 mice (blank group) were respectively randomized into control and EA groups. EA (2 Hz/15 Hz, 1ï¼2 mA) was applied to GV20 and bilateral BL23 for 30 min, once daily, 6 days a week for 4 weeks. The recognition memory ability was detected by novel object recognition tests in a behavior test box. The percentage of time spent in close interaction with novel object (C) relative to the total time was used to generate preference index. The contents of hippocampal ß amyloid protein (Aß)1-40 and Aß1-42 were assayed using ELISA, and the expression levels of glial fibrillary acidic protein (GFAP), ionic calcium binding receptor molecule-1 (Iba-1), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) proteins in the hippocampus measured by Western blot. The activities of hippocampal astrocytes (GFAP-labelled cells), microglia (Iba-1-labelled cells) and the polarity expression of AQP4 (for removing Aß) were measured by immunohistochemistry. RESULTS: The preference index was significantly decreased in the model group relatively to the blank control group (P<0.05) and considerably increased in the modelï¼EA group relatively to the model group (P<0.05), suggesting an improvement of the recognition memory after EA. The contents of Aß1-40 and Aß1-42, immunoactivity of GFAP and Iba-1, expression levels of GFAP, Iba-1, IL-1ß, IL-6 and TNF-α proteins were significantly higher in the model group than in the blank control group (P<0.01ï¼P<0.05), while the AQP4 immunoactivity was notably lower in the model group than in the blank control group (P<0.05). Compared with the model group, the levels of Aß1-40 and Aß1-42, GFAP, Iba-1, IL-1ß, IL-6 and TNF-α proteins, and the percentage of Aß plaque area were significantly decreased in the modelï¼EA group (P<0.01ï¼P<0.05), and the immunoactivity of AQP4 was significantly increased in the mo-delï¼EA group (P<0.05). No significant changes were found in the above-mentioned indexes in the blankï¼EA group relevant to the blank control group (P>0.05)ï¼. CONCLUSION: EA at GV20 and BL23 can reduce inflammatory reaction and Aß level, suppress activation of astrocytes and microglia, and up-regulate expression of AQP4 in the hippocampus tissue in APP/PS1 transgenic mice, which may contribute to its effect in improving recognition memory ability, suggesting a role of EA intervention in delaying the development of AD via promoting the drainage of Aß by the glymphatic system in the brain.
