Journal
NEURAL REGENERATION RESEARCH
Volume 17, Issue 9, Pages 2072-2078Publisher
WOLTERS KLUWER MEDKNOW PUBLICATIONS
DOI: 10.4103/1673-5374.335168
Keywords
(D-ser2) oxyntomodulin; Alzheimer's disease; cognitive decline; glucagon-like peptide-1; hippocampus; local field potential; synapse; theta rhythm
Categories
Funding
- National Natural Science Foundation of China [31600865]
- Sanjin Scholars of Shanxi Province of China [[2016]7]
- Shanxi Province Science Foundation for Excellent Young Scholars of China [201801D211005]
- Applied Basic Research Program of Shanxi Province of China [201901D111358]
- Doctoral Startup Research Fund of Shanxi Medical University of China [03201536]
- Doctoral Startup Research Fund of the First Hospital of Shanxi Medical University of China [YJ1507]
- National Undergraduate Innovation Program of China [201910114019]
- Undergraduate Innovation Program of Shanxi Province of China [2020189]
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(D-Ser2) Oxyntomodulin improves cognitive function in Alzheimer's disease transgenic mice by restoring hippocampal synaptic function and theta rhythm.
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 A beta(1-42)-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 3xTg 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 3xTg 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.
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