Objective To observe the effects of electro-acupuncture on open field behaviors and the expression of brain-derived neurotrophic factor (BDNF) and presenilin 1 (PS1) proteins in the hippocampus tissue of amyloid precursor protein/presenilin 1 (APP/PS1) double-transgenic mice, and explore the mechanism of electro-acupuncture intervention in improving Alzheimer disease (AD). Methods Twelve APP/PS1 double-transgenic mice were divided into electro-acupuncture group (EG) and restraint group (RG) with 6 mice in each group according to the random number table method. Meanwhile, another 6 wild-type mice with the same age and sex were selected as the blank control group (WT). Mice in the EG were treated with electro-acupuncture at Baihui, bilateral Zusanli and Neiguan acupoints once a day, five days weekly. Following the first week of intervention, a one-week rest interval was arranged prior to the second round of treatment. Each treatment course lasted three weeks, and three courses were completed in total. Mice in the WT and RG received grasping and restraint for 20 minutes per session without electro-acupuncture, matching the intervention schedule of the EG. After three courses of treatment, the SMART 3.0 small animal behavioral analysis system was used to detect the total traveling distance (total distance), traveling distance in the central zone (central distance), number of entries into the central zone (number of central entries), and total residence time in the central zone (central residence time) for mice in each group within 6 minutes. The spontaneous activity and exploratory ability of mice were evaluated combined with movement trajectories and 3D thermal imaging maps. Immunohistochemistry was adopted to detect the expression levels of BDNF and PS1 proteins in the hippocampal tissues of mice, and RNA sequencing was performed to analyze differentially expressed genes among the three groups. Results There was a statistically significant difference in the total distance among the three groups, and the total distance in the RG was shorter than that in the WT (P<0.05). No significant differences were observed in central distance, number of central entries and central residence time among the three groups (P>0.05). The movement trajectories and 3D thermal imaging maps of mice showed that the WT exhibited more complex movement trajectories and higher activity levels in the central zone compared with the RG and EG. The movement trajectories and central zone activity of mice in the EG were superior to those in the RG. There was a statistically significant difference in the optical density value of BDNF protein expression among the three groups. The optical density values of BDNF protein expression in the EG and RG were lower than those in the WT, and the EG was higher than the RG (P<0.05). No statistically significant difference was found in the optical density value of PS1 protein expression among the three groups (P>0.05). RNA sequencing results indicated that differentially expressed genes existed in the hippocampal tissues of mice in each group. Conclusion Electro-acupuncture intervention improves locomotor activity and exploratory behavior in APP/PS1 double-transgenic mice and elevates hippocampal BDNF protein expression. It suggests that electro-acupuncture may retard the pathological progression of AD via modulating BDNF protein levels.

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