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In order to evaluate the antidepressant effect of electroacupuncture (EA) on the rat model of chronic unpredictable stress (CUS) and the proliferation promoting effect on stem / progenitor cells in the dentate gyrus (DG) of hippocampus, this study investigated the behavioral and brain section staining changes of 4 groups (normal, Model, Sham EA and EA).After 2 weeks of CUS procedure, EA, as well as Sham EA, was performed on Du-20 (Bai-Hui) and GB-34 (Yang-Ling-Quan) for 15 d (8 treatments in all).Forced swimming test (FST), elevated plus-maze (EPM) test and open field test (OFT) suggested that EA had reversed the depressive like behavior.Interestingly, Sham EA, as designed on the real acupoints without electrical current, also showed a little antidepressant effect.As shown by 5-bromo-2-deoxyuridine (BrdU) and SOX-2 double-labeling immunofluorescence, proliferation of DG stem cells was decreased in model group.Compared with the depression model, the decrease of stem-cell proliferation in both Sham EA and EA groups had begun to be significantly blocked since 2 treatments were carried out.Taking the subpopulations of stem cells into consideration, we found that EA could up-regulate both quiescent neural progenitors (QNPs, SOX-2 positive and GFAP positive) and amplifying neural progenitors (ANPs, SOX-2 positive but GFAP negtive) in DG while Sham EA could only promote the latter, through SOX-2 and GFAP double staining.We further demonstrated that both Sham EA and EA increased p-ERK and SOX-2 double positive cells number and the both groups had the increasing effect at the same level.But the EA group had a lower ratio of p-ERK in SOX-2 in respect that the total stem cell number was larger.These results suggest that EA has the antidepressant effect mediated by promoting both QNPs and ANPs in DG and that acupuncture could treat depression by activating ANPs, ERK as a possible passway to through.Some other passways may be included in the mechanism of EA antidepressant effect.