BACKGROUND:Alzheimer's disease is a degenerative neurological disorder characterized primarily by cognitive impairment.Acupuncture is a kind of traditional Chinese medicine therapy for treating Alzheimer's disease,but its mechanism is not yet clear. OBJECTIVE:To observe the effects of electroacupuncture with"Zhi San Zhen"on the Notch signaling pathway,β-amyloid protein(Aβ)and synaptic plasticity in 5xFAD mice. METHODS:Sixteen male,6-month-old 5xFAD mice,SPF-grade,were randomly divided into the electroacupuncture with"Zhi San Zhen"group(electroacupuncture group)and the model group,with eight mice in each group.Eight SPF-grade,male,6-month-old C57BL/6 mice were used as the wild control(wild)group.The electroacupuncture group received electroacupuncture with"Zhi San Zhen"intervention,5 times a week for 4 consecutive weeks.The model group and the wild group did not receive electroacupuncture intervention.The Morris water maze was used to preliminarily assess their learning and memory abilities.Thioflavin S staining was performed to detect Aβ plaque deposition.Western blot and real-time quantitative polymerase chain reaction(RT-qPCR)were used to measure the expression levels of transmembrane receptor protein Notch-1,Notch 1 intracellular domain(NICD),hairy and enhancer of split 1(Hes 1),hairy and enhancer of split 5(Hes 5),synaptophysin(SYN),postsynaptic density protein-95(PSD-95),and Aβ. RESULTS AND CONCLUSION:Compared with the model group,the wild group and the electroacupuncture group showed shortened escape latency,increased platform crossing times,and longer target quadrant dwell time(P<0.05).Compared with the wild group,the model group had significantly increased deposition of Aβ plaques,while electroacupuncture with"Zhi San Zhen"inhibited the deposition of Aβ plaques in the hippocampus of 5xFAD mice(P<0.05).Compared with the wild group,the model group had decreased mRNA levels of SYN,PSD-95,Notch 1,NICD,Hes 1,and Hes 5 in the hippocampal tissue of mice,and increased mRNA levels of Aβ(P<0.05).Electroacupuncture with"Zhi San Zhen"increased the mRNA levels of SYN,PSD-95,Notch 1,NICD,Hes 1,and Hes 5 in the hippocampal tissue,and decreased the mRNA level of Aβ(P<0.05).Compared with the Wild group,the model group had decreased protein expression levels of SYN,PSD-95,Notch 1,NICD,Hes 1,and Hes 5 in the hippocampal tissue of mice,and increased protein expression levels of Aβ(P<0.05).Electroacupuncture with"Zhi San Zhen"upregulated the protein expression levels of SYN,PSD-95,Notch 1,NICD,Hes 1,and Hes 5,and inhibited the protein expression of Aβ(P<0.05).To conclude,electroacupuncture with"Zhi San Zhen"can improve the learning and memory abilities of 5xFAD mice,possibly by inhibiting the deposition of Aβ protein and activating the Notch signaling pathway in the hippocampus to enhance synaptic plasticity.