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A dual GLP-1 and Gcg receptor agonist rescues spatial memory and synaptic plasticity in APP/PS1 transgenic mice
| Content Provider | Semantic Scholar |
|---|---|
| Author | Wang, Zhaojun Zhao, Fang Yang, Guangzhao Wu, Mei-Na |
| Copyright Year | 2020 |
| Abstract | Alzheimer's disease (AD) is a neurodegenerative disease that severely affects the health and lifespan of the elderly worldwide. Recently, the correlation between AD and type 2 diabetes mellitus (T2DM) has received intensive attention, and a promising new anti-AD strategy is the use of anti-diabetic drugs. Oxyntomodulin (Oxm) is a peptide hormone and growth factor that acts on neurons in the hypothalamus. OXM activates glucagon-like peptide 1 (GLP-1) and glucagon (Gcg) receptors, facilitates insulin signaling and has neuroprotective effects against Aβ1-42-induced cytotoxicity in primary hippocampal neurons. Here, we tested the effects of the protease-resistant analogue (D-Ser2)Oxm on spatial memory and synaptic plasticity and the underlying molecular mechanisms in the APP/PS1 transgenic mouse model of AD. The results showed that (D-Ser2)Oxm not only alleviated the impairments of working memory and long-term spatial memory, but also reduced the number of Aβ plaques in the hippocampus, and reversed the suppression of hippocampal synaptic long-term potentiation (LTP). Moreover, (D-Ser2)Oxm administration significantly increased p-PI3K/p-AKT1 expression and decreased p-GSK3β levels in the hippocampus. These results are the first to show an in vivo neuroprotective role of (D-Ser2)Oxm in APP/PS1 mice, and this role involves the improvement of synaptic plasticity, clearance of Aβ and normalization of PI3K/AKT/GSK3β cell signaling in the hippocampus. This study suggests that (D-Ser2)Oxm holds promise for the prevention and treatment of AD. |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/j.yhbeh.2019.104640 |
| Alternate Webpage(s) | https://api.elsevier.com/content/article/pii/S0018506X19304477 |
| Alternate Webpage(s) | https://www.sciencedirect.com/science/article/pii/S0018506X19304477?dgcid=api_sd_search-api-endpoint |
| PubMed reference number | 31765661 |
| Alternate Webpage(s) | https://doi.org/10.1016/j.yhbeh.2019.104640 |
| Journal | Medline |
| Volume Number | 118 |
| Journal | Hormones and Behavior |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
