关键词: 阿尔茨海默病, 电针, 小鼠, 学习记忆, 神经元, 少突胶质细胞, Notch通路

Abstract: BACKGROUND: The effect of electroacupuncture on the proliferation and differentiation of hippocampal oligodendrocytes in model mice with Alzheimer’s disease remains poorly understood while demyelinating reaction related to oligodendrocytes is a common pathological reaction of Alzheimer’s disease.
OBJECTIVE: To investigate the effects and mechanism of electroacupuncture stimulation of “Baihui” (GV 20), “Fengfu” (GV 16) and bilateral “Shenshu” (BL 23) in Alzheimer’s disease model mice on the proliferation and differentiation of endogenous neural stem cells to neurons and oligodendrocytes.
METHODS:  Forty 6-week-old SPF APP/PS1 transgenic male Alzheimer’s disease model mice were randomly divided into electroacupuncture group(n=20) and Alzheimer’s disease model group (n=20). Healthy male C57BL/6J mice of the same age were used as normal controls (n=20). The mice in the electroacupuncture group received electroacupuncture at “Baihui” (GV 20), “Fengfu” (GV 16) and bilateral “Shenshu” (BL 23) for 16 weeks (20 minutes/day and one day off a week). After electroacupuncture, Morris water maze was used to detect the changes of learning and memory function. Immunohistochemistry was utilized to detect hippocampal dentate gyrus β-amyloid senile plaques. The expression of BrdU/NeuN and BrdU/GALC in the hippocampal dentate gyrus was detected by immunofluorescence double labeling. Western blot assay was used to detect the expression levels of neuron specific protein Nestin and oligodendrocyte specific protein GALC in the hippocampus. mRNA and protein levels of Notch1 and Hes1 in the hippocampus were detected by real-time fluorescence quantitative PCR and western blot assay. 
RESULTS AND CONCLUSION: (1) Compared with the normal control group, the ability of learning and memory in the Alzheimer’s disease model group decreased significantly; hippocampal dentate gyrus β-amyloid senile plaques increased significantly (P < 0.01); the expression of GALC and Nestin in the hippocampus decreased significantly (P < 0.01, P < 0.05). (2) Compared with the Alzheimer’s disease model group, the learning and memory ability of the electroacupuncture group was significantly increased; β-amyloid senile plaque in the hippocampal dentate gyrus decreased significantly (P < 0.01). BrdU/NeuN double labeled positive cells in the hippocampal dentate gyrus and Nestin protein expression in the hippocampus increased significantly (P < 0.01, P < 0.05); GALC expression in hippocampus increased significantly (P < 0.01). The mRNA and protein levels of Notch1 in the hippocampus were significantly increased (P < 0.05, P < 0.01). The mRNA and protein levels of Hes1 in the hippocampus decreased significantly (P < 0.05). (3) These findings indicate that electroacupuncture at “Baihui” (GV 20), “Fengfu” (GV 16) and bilateral “Shenshu” (BL 23) of the Alzheimer’s disease model infant mice can promote the proliferation and differentiation of endogenous neural stem cells to neurons and oligodendrocytes, which may be regulated through the Notch1/Hes1 pathway.

Key words: Alzheimer’s disease, electroacupuncture, mice, learning and memory, neuron, oligodendrocyte, Notch pathway