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The aim of the present study was to compare the effects of α-lipoic acid (ALA) on postoperative cognitive dysfunction (POCD) between wild type (WT) and leptin receptor-deficient (db/db) mice and to elucidate the underlying mechanism of treatment with ALA. The present study compared the effects of ALA on spatial learning and memory of WT and db/db mice using a Morris water maze following hepatectomy. The expression levels of proteins, including cyclin-dependent kinase 5 (Cdk5), tau, phosphorylated tau and amyloid β (Aβ) were measured in the hippocampus. Surgery impaired postoperative cognitive function in both WT and db/db mice. Furthermore, the expression levels of Cdk5 and Aβ, and the phosphorylation of tau in the hippocampus increased after the surgery in both WT and db/db mice. The ultrastructure of hippocampal neurons and synapses was analyzed by transmission electron microscopy and the results revealed that surgery damaged the structure of neurons and synapses in both WT and db/db mice. Treatment with ALA protected the postoperative cognitive function and the structure of hippocampal neurons and synapses, and prevented the increase in protein expression levels of Cdk5 and Aβ, and the phosphorylation of tau in the hippocampus of WT but not db/db mice. The results of the present study suggest that ALA may be used for the treatment of POCD. The molecular mechanisms underlying the activity of ALA require further investigation.

α‑lipoic acid attenuates spatial learning and memory impairment induced by hepatectomy