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Orexin A (OxA) has been reported to show abnormally elevated expression in the cerebrospinal fluid (CSF) of patients with Alzheimer\u2019s disease (AD) and to be associated with cognitive impairment. Here, we further assessed whether the excitatory neurotransmitter OxA is involved in neuroplasticity and cognitive function in senescence\u2010accelerated mouse prone 8 (SAMP8) mice. In this study, we investigated the mechanism of OxA by using behavioral tests, CSF microdialysis, immunofluorescence, toluidine blue staining, gene silencing, transmission electron microscopy, and Western blotting. The results showed that 10\u2009Hz electroacupuncture (EA) effectively alleviated learning and memory impairment in 7\u2010month\u2010old SAMP8 mice, reduced OxA levels in the CSF, increased the level of the neurotransmitter glutamate, alleviated pathological damage to hippocampal tissue, improved the synaptic structure, enhanced synaptic transmission, and regulated the expression of cAMP\/PKA\/CREB signaling pathway\u2010related proteins. These results suggest that EA enhances neuroplasticity in SAMP8 mice by regulating the OxA\u2010mediated cAMP\/PKA\/CREB signaling pathway, thus improving cognitive function. These findings suggest that EA may be beneficial for the prevention and treatment of age\u2010induced cognitive impairment.<\/jats:p>","DOI":"10.1155\/2022\/8694462","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T19:05:07Z","timestamp":1644001507000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Electroacupuncture Enhances Neuroplasticity by Regulating the Orexin A\u2010Mediated cAMP\/PKA\/CREB Signaling Pathway in Senescence\u2010Accelerated Mouse Prone 8 (SAMP8) 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