To explore the effect of sesamol on the cognition of APP/PS1 mice, 8-week-old APP/PS1 and wild-type male mice were divided into AD model group, AD + sesamol (50 mg kg−1 bw) group, and Control group. Sesamol was orally administered once a day for 5 months. Morris water maze was used to evaluate the learning and memory ability of mice. The number of synapses in the hippocampal neurons was detected by Golgi staining. Nissl staining was used to observe the changes of Nissl bodies in CA1 and CA3 regions of the hippocampus. Western blotting was used to detect the expression of Aβ, SIRT1, BDNF, and p-CREB/CREB in the hippocampus and cortex. Compared with the model group, sesamol decreased the latency period of APP/PS1 mice (P < 0.05) and increased the total number of neuronal dendritic spines in the hippocampal CA3 region, as well as increased the number of Nissl bodies (P < 0.05). Western blotting results showed that sesamol significantly reduced Aβ protein expression in the hippocampus and cortex, increased SIRT1 expression in the cortex, and increased BDNF expression in the hippocampus (P < 0.05). Sesamol improved the learning and memory abilities of APP/PS1 mice probably through increasing the density of neuronal dendritic spines and upregulating the levels of SIRT1 and BDNF.
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