关键词: 阿尔茨海默病, 电针, 心包经穴, 功能连接, 神经递质

Abstract:

Objective To explore the effect of electroacupuncture at the Neiguan and Jianshi acupoints on the brain functional network connectivity in APP/PS1 mice. Methods A total of 18 5-month-old SPF-grade male mice were selected， among which 12 model mice carrying the APP/PS1 double transgenic were randomly divided into two groups according to the random number table method： the model group （n = 6） and the electroacupuncture group （n = 6）. Additionally， 6 C57BL/6 mice with the same genetic background were selected as the control group. The mice in the electroacupuncture group were given electroacupuncture intervention at the "Neiguan" and "Jianshi" acupoints. The electroacupuncture device was connected to the acupoints on the same side， and the acupoints on both sides were alternately used once every other day for a total of 5 weeks. After electroacupuncture， the spatial learning and memory ability of mice in each group was detected by Morris water maze， and the non-spatially dependent memory ability of mice in each group was observed by new object recognition. Taking the bilateral hippocampus as the region of interest （ROI）， resting-state functional magnetic resonance imaging （rs-fMRI） was used to analyze the functional connectivity between the hippocampus and the whole brain. The changes in the contents of norepinephrine （NE） and dopamine （DA） in the hippocampus and prefrontal cortex were detected by ELISA. The expression levels of glycogen synthase kinase 3β （GSK-3β） and synaptic protein I（SynI） in the hippocampus were detected by Western blot. Results Compared with the control group， the latency of mice in the model group was prolonged （P < 0.01）， the number of platform crossings and the exploration time of the target quadrant decreased （P < 0.01）， and the cognitive index decreased （P < 0.01）. Compared with the model group， the latency of mice in the electroacupuncture group was shortened （P < 0.01）， the number of platform crossings and the exploration time of the target quadrant were both increased （P < 0.01）， and the cognitive index was elevated （P < 0.01）. Compared with the control group， the functional connections of the transition area between the right hippocampus and the left posterior piriform region， the right central amygdala， the left dentate gyrus， the right entorhinal region， and the right main olfactory bulb in the model group mice were decreased. Compared with the model group， the functional connections of the transition area between the right hippocampus and the left posterior piriform region， the right central amygdala， the transition area of the right posterior piriform region， the left dentate gyrus， the right main olfactory bulb， and the left main olfactory bulb in the electroacupuncture group were increased. The functional connections between the left hippocampus and the right lateral nucleus， the right hippocampal subCA3， the left main olfactory bulb， and the left entorhinal area were elevated. Compared with the control group， the contents of NE and DA in the hippocampus of mice in the model group decreased （P < 0.05）， and the contents of NE and DA in the prefrontal cortex decreased （P < 0.05）. Compared with the model group， the contents of NE and DA in the hippocampus of mice in the electroacupuncture group increased （P < 0.05）， and those in the prefrontal cortex increased （P < 0.05）. Compared with the control group， the expression of GSK-3β in the hippocampus of mice in the model group increased and the expression of SynI decreased （P < 0.05）. Compared with the model group， the expression of GSK-3β in the hippocampus of mice in the electroacupuncture group decreased and the expression of SynI increased （P < 0.05）. Conclusions Electroacupuncture at the pericardium acupoint can restore the functional connectivity between the hippocampus and other brain regions in APP/PS1 mice. The mechanism may be related to the disorder of neurotransmitters regulating the key brain regions of AD.

Key words: Alzheimer's disease, electroacupuncture, pericardium meridian points, functional connectivity, neurotransmitters