(D-Ser2) oxyntomodulin recovers hippocampal synaptic structure and theta rhythm in Alzheimer's disease transgenic mice

• Published in: Neural regeneration research Vol. 17; no. 9; pp. 2072 - 2078
• Main Authors: Yang, Guang-Zhao, Gao, Qi-Chao, Li, Wei-Ran, Cai, Hong-Yan, Zhao, Hui-Min, Wang, Jian-Ji, Zhao, Xin-Rui, Wang, Jia-Xin, Wu, Mei-Na, Zhang, Jun, Hölscher, Christian, Qi, Jin-Shun, Wang, Zhao-Jun
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.09.2022; Medknow Publications & Media Pvt. Ltd; Department of Cardiovascular Medicine,the First Hospital of Shanxi Medical University,Taiyuan,Shanxi Province,China%Department of Physiology,Shanxi Medical University; Key Laboratory of Cellular Physiology in Shanxi Province,Taiyuan,Shanxi Province,China%Department of Microbiology and Immunology,Shanxi Medical University,Taiyuan,Shanxi Province,China%Functional Laboratory Center,Shanxi Medical University,Taiyuan,Shanxi Province,China%Research and Experimental Center,Henan University of Chinese Medicine,Zhengzhou,Henan Province,China; Key Laboratory of Cellular Physiology,Ministry of Education; Wolters Kluwer - Medknow; Wolters Kluwer Medknow Publications
• Subjects: (d-ser2) oxyntomodulin; alzheimer’s disease; cognitive decline; glucagon-like peptide-1; hippocampus; local field potential; synapse; theta rhythm; Alzheimer's disease; Glucagon; Peptides; Rodents; Transgenic animals; (D-ser2) oxyntomodulin; local field potential; Alzheimer’s disease; hippocampus; glucagon-like peptide-1; synapse; cognitive decline; theta rhythm; (D-ser2) oxyntomodulin Alzheimer s disease
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.335168

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.