IMR Press / JIN / Volume 20 / Issue 1 / DOI: 10.31083/j.jin.2021.01.224
Open Access Original Research
“Olfactory three-needle” acupuncture enhances synaptic function in A𝜷1-42-induced Alzheimer’s disease via activating PI3K/AKT/GSK-3𝜷 signaling pathway
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1 College of Acu-moxibustion and Massage, Shaanxi University of Chinese Medicine, 712046 Xianyang, P. R. China
2 Shaanxi Key Laboratory of Acupuncture and Medicine, 712046 Xianyang, P. R. China
3 Department of Acupuncture, Rehabilitation, Massage and Pain, the Second Affiliated Hospital of Shaanxi University of Chinese Medicine, 712000 Xianyang, P. R. China
4 Department of Traditional Chinese Medicine, BaoTou Medical College, 014040 Baotou, P. R. China
*Correspondence: (Zhi-Bin Liu)
These authors contributed equally.
J. Integr. Neurosci. 2021, 20(1), 55–65;
Submitted: 22 July 2020 | Revised: 23 November 2020 | Accepted: 4 December 2020 | Published: 30 March 2021
Copyright: © 2021 The Authors. Published by IMR Press.
This is an open access article under the CC BY 4.0 license (

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-amyloid1-42 (Aβ1-42)-induced Alzheimer’s disease rats. A three-needle olfactory bulb insertion for 28 days alleviated Aβ1-42-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.

Alzheimer's disease
Olfactory bulb
Synaptic plasticity
PI3K/AKT/GSK-3β signaling
Fig. 1.
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