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BACKGROUND Alzheimer's disease (AD) is an age-associated neurodegenerative disorder. This study aimed to investigate effects of acupuncture administration on cognitive function and associated mechanisms. MATERIAL AND METHODS Senescence-accelerated prone 8 (SAM-P8) mice were randomly divided into 3 groups: the SAM-P8 group (P8-CN), the SAM-P8 administrating with acupuncture (P8-Acup) group, and the SAM-P8 administrating without acupuncture (P8-Sham) group. Morris water maze test was conducted to evaluate cognitive functions (memory and learning ability). PDK1, nPKC, and Rac1 inhibitors were used to treat SAM-P8 mice. Transmission electron microscope analysis was used to examine nuclear damage hippocampal tissues. Hematoxylin and eosin (H&amp;E) staining was employed to evaluate inflammation. Western blot was used to detect PI3K, PDK1, nPKC, and Rac 1 expression in hippocampal tissues. RESULTS Acupuncture administration significantly reduced PI3K, PDK1, nPKC, and Rac 1 levels compared to P8-CN group (P&lt;0.05). Both acupuncture and enzyme inhibitors (NSC23766, Rottlerin, OSU03012) significantly improved cognitive functions, reduced inflammation, and alleviated nuclear damages of SAM-P8 mice compared to P8-CN group (P&lt;0.05). Acupuncture significantly enhanced effects of inhibitors on inflammation and nuclear damages compared to inhibitor treatment single (P&lt;0.05). Acupuncture significantly enhanced down-regulative effects of OSU03012 on PI3K and PDK1 levels, increased down-regulative effects of Rottlerin on nPKC and Rac 1 levels and enhanced effects of Rottlerin on Rac 1 compared to P8-CN group (P&lt;0.05). CONCLUSIONS Acupuncture administration improved cognitive functions and alleviated inflammatory response and nuclear damage of SAM-P8 mice, by downregulating PI3K/PDK1/nPKC/Rac 1 signaling pathway. This study could provide potential insight for treating cognitive dysfunction and aging of AD patients.

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Acupuncture Administration Improves Cognitive Functions and Alleviates Inflammation and Nuclear Damage by Regulating Phosphatidylinositol 3 Kinase (PI3K)/Phosphoinositol-Dependent Kinase 1 (PDK1)/Novel Protein Kinase C (nPKC)/Rac 1 Signaling Pathway in Senescence-Accelerated Prone 8 (SAM-P8) Mice