Objective To investigate the protection mechanism of electroacupuncture(EA)therapy against Alzheimer's disease(AD)-like neurotoxicity induced by Isoflurane.Methods Twenty-four APPswe/PS 1dE 9double transgenic mice(one of the most extensively used transgenic mouse model of AD)and 24 littermate wild-type mice were randomly assigned into control(Con)group

isoflurane(Iso)group and EA group

respectively(n=8in each group).EA(2Hz/100 Hz

1mA)was applied to"Baihui"(GV 20)and"Yongquan"(KI 1)for 15 min

once a day for 3days.The transgenic mice were exposed to a closed box filled with 1.2%Isoflurane+30% O2+70% N2 for 4h.The animals' learning-memory ability was detected by Morris water maze test.The expression of cleaved Caspase-3in the CA 1area of hippocampus was detected by immunohistochemistry

and that of hippocampal Bcl-2and Bax proteins detected by Western blot.Results Compared with the wilde-type mice

the average escape latency of place navigation test was significantly longer

while the percentage of target-quadrant stay time and the targetplatform crossing times of spacial probe test were marked decreased in AD+Iso mice(P<0.05).After acupuncture intervention

the abovementioned changes were reversed(P<0.05).Correspondingly

compared with the AD-Con group

the number of hippocampal activated Caspase-3-positive cells and the expression of Bax protein were significantly increased in the AD-Iso group(P<0.05).After EA intervention

the increased Caspase-3-positive cell number and Bax protein expression were remarkably down-regulated in the AD-EA group

and the decreased ratio of Bcl-2/Bax in AD-Iso mice was obviously up-regulated in AD-EA mice(P<0.05).No significant changes were found in the average escape latency

the percentage of target-quadrant stay time and the target-platform crossing times

and in the number of hippocampal activated Caspase-3-positive cells

the expression levels of hippocampal Bcl-2and Bax and the ratio of Bcl-2/Bax in the three groups of wilde-type mice(P>0.05).ConclusionEA intervention can improve the learning-memory ability in AD+Isoflurane mice

suggesting a reduction of AD-like neurotoxicity

which may be associated with its actions in inhibiting the overexpression of activated Caspase-3and Bax proteins in the hippocampus.