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

1-2 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 β amyloid protein(Aβ)_(1-40) and Aβ_(1-42) were assayed using ELISA

and the expression levels of glial fibrillary acidic protein(GFAP)

ionic calcium binding receptor molecule-1(Iba-1)

interleukin-1β(IL-1β)

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 Aβ) 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 model+EA group relatively to the model group(P<0.05)

suggesting an improvement of the recognition memory after EA. The contents of Aβ_(1-40) and Aβ_(1-42)

immunoactivity of GFAP and Iba-1

expression levels of GFAP

Iba-1

IL-1β

IL-6 and TNF-α proteins were significantly higher in the model group than in the blank control group(P<0.01

P<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 Aβ_(1-40) and Aβ_(1-42)

GFAP

Iba-1

IL-1β

IL-6 and TNF-α proteins

and the percentage of Aβ plaque area were significantly decreased in the model+EA group(P<0.01

P<0.05)

and the immunoactivity of AQP4 was significantly increased in the mo-del+EA group(P<0.05). No significant changes were found in the above-mentioned indexes in the blank+EA group relevant to the blank control group(P>0.05).Conclusion EA at GV20 and BL23 can reduce inflammatory reaction and Aβ 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 Aβ by the glymphatic system in the brain.