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A dual GLP-1 and Gcg receptor agonist rescues spatial memory and synaptic plasticity in APP/PS1 transgenic mice
Wang ZJ, Han YF, Zhao F, Yang GZ, Yuan L, Cai HY, Yang JT, Holscher C et al.. Hormones and behavior, 2019-11-28
Topic: Brain proteins, microglia and lab models
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 Aβ 1 - 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.
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APA 7th
Wang, Z. J., Han, Y. F., Zhao, F., Yang, G. Z., Yuan, L., Cai, H. Y., et al. (2020). A dual GLP-1 and Gcg receptor agonist rescues spatial memory and synaptic plasticity in APP/PS1 transgenic mice. Hormones and behavior. https://doi.org/10.1016/j.yhbeh.2019.104640
Vancouver
Wang ZJ, Han YF, Zhao F, Yang GZ, Yuan L, Cai HY, et al. A dual GLP-1 and Gcg receptor agonist rescues spatial memory and synaptic plasticity in APP/PS1 transgenic mice. Hormones and behavior. 2020. doi:10.1016/j.yhbeh.2019.104640. PMID: 31765661.
BibTeX
@article{wang2020-31765661,
author = {Wang, Z. J. and Han, Y. F. and Zhao, F. and Yang, G. Z. and Yuan, L. and Cai, H. Y. and Yang, J. T. and Holscher, C. and others},
title = {{A dual GLP-1 and Gcg receptor agonist rescues spatial memory and synaptic plasticity in APP/PS1 transgenic mice}},
journal = {Hormones and behavior},
year = {2020},
doi = {10.1016/j.yhbeh.2019.104640},
pmid = {31765661},
url = {https://doi.org/10.1016/j.yhbeh.2019.104640}
}
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Key findings
- 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.
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Study details
- Evidence strengthLow
How this study scored 38/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 22 of the 58 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Hormones and behavior) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “app/ps1”) — scores zero |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31765661) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 22 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 22 of the 58 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
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