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Synaptic dysfunction and neuronal loss are related to cognitive impairment of Alzheimer's disease. Recent evidence indicates that regulating the phosphatidylinositol 3-Kinase (PI3K)/AKT/GSK-3β pathway is a therapeutic strategy for improving synaptic plasticity in Alzheimer's disease. Here, we investigated "olfactory three-needle" effects on synaptic function and the PI3K/AKT/GSK-3β signaling pathway in β-amyloid 1-42 (Aβ 1-42 )-induced Alzheimer's disease rats. A three-needle olfactory bulb insertion for 28 days alleviated Aβ 1-42 -induced Alzheimer's disease rats' cognitive impairment as assessed by performance in the Morris water maze test. Furthermore, the three-needle electrode inhibited neuro-apoptosis and neuro-inflammation. It significantly upregulated the protein expression of postsynaptic density protein 95, synaptophysin, and GAP43, indicating a protective effect on hippocampal synaptic plasticity. Additionally, the activation level of PI3K/AKT signaling and the phosphorylation inactivation of GSK-3β were significantly enhanced by the "olfactory three-needle". Our findings suggested that the three-needle acupuncture is a potential alternative to improve synaptic plasticity and neuronal survival of Alzheimer's disease brain in rodents.

“Olfactory three-needle” acupuncture enhances synaptic function in A𝜷1-42-induced Alzheimer’s disease via activating PI3K/AKT/GSK-3𝜷 signaling pathway