摘要
In our previous studies,we have shown that(D-Ser2)oxyntomodulin(Oxm),a glucagon-like peptide 1(GLP-1)receptor(GLP1R)/glucagon receptor(GCGR)dual agonist peptide,protects hippocampal neurons against Aβ1-42-induced cytotoxicity,and stabilizes the calcium homeostasis and mitochondrial membrane potential of hippocampal neurons.Additionally,we have demonstrated that(D-Ser2)Oxm improves cognitive decline and reduces the deposition of amyloid-beta in Alzheimer’s disease model mice.However,the protective mechanism remains unclear.In this study,we showed that 2 weeks of intraperitoneal administration of(D-Ser2)Oxm ameliorated the working memory and fear memory impairments of 9-month-old 3×Tg Alzheimer’s disease model mice.In addition,electrophysiological data recorded by a wireless multichannel neural recording system implanted in the hippocampal CA1 region showed that(D-Ser2)Oxm increased the power of the theta rhythm.In addition,(D-Ser2)Oxm treatment greatly increased the expression level of synaptic-associated proteins SYP and PSD-95 and increased the number of dendritic spines in 3×Tg Alzheimer’s disease model mice.These findings suggest that(D-Ser2)Oxm improves the cognitive function of Alzheimer’s disease transgenic mice by recovering hippocampal synaptic function and theta rhythm.
基金
supported by the National Natural Science Foundation of China,No.31600865(to ZJW)
“Sanjin Scholars”of Shanxi Province of China,No.[2016]7(to MNW)
Shanxi Province Science Foundation for Excellent Young Scholars of China,No.201801D211005(to MNW)
the Applied Basic Research Program of Shanxi Province of China,No.201901D111358(to GZY)
the Doctoral Startup Research Fund of Shanxi Medical University of China,No.03201536(to GZY)
the Doctoral Startup Research Fund of the First Hospital of Shanxi Medical University of China,No.YJ1507(to GZY)
the National Undergraduate Innovation Program of China,No.201910114019(to JXW)
the Undergraduate Innovation Program of Shanxi Province of China,No.2020189(to XRZ).
