Open Access(D-Ser2) oxyntomodulin recovers hippocampal synaptic structure and theta rhythm in Alzheimer’s disease transgenic mice
Author(s) -
Gang Yang,
Qi-Chao Gao,
Weiran Li,
Hong-Yan Cai,
Huimin Zhao,
Jianji Wang,
Xinrui Zhao,
Jiaxin Wang,
MeiNa Wu,
Jun Zhang,
Christian Hölscher,
Jin-Shun Qi,
Zhaojun Wang
Publication year - 2022
Publication title -
neural regeneration research/neural regeneration research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.93
H-Index - 38
eISSN - 1876-7958
pISSN - 1673-5374
DOI - 10.4103/1673-5374.335168
Subject(s) - hippocampal formation , synaptic plasticity , long term potentiation , neuroscience , agonist , alzheimer's disease , endocrinology , cognitive decline , hippocampus , amyloid beta , spontaneous alternation , neuroprotection , medicine , chemistry , psychology , receptor , dementia , disease
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 Aβ 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 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.