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Memantine ameliorates cognitive deficit in AD mice via enhancement of entorhinal–CA1 projection

BACKGROUND: Memantine, a low- to moderate-affinity uncompetitive N-methyl-D-aspartate receptor antagonist, has been shown to improve cognitive functions in animal models of Alzheimer’s disease (AD). Here we treated APP/PS1 AD mice with a therapeutic dose of memantine (20 mg/kg/day) and examined its...

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Autores principales: Li, Peng, Xu, Jin, Gu, Huanhuan, Peng, Hua, Yin, You, Zhuang, Jianhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201811/
https://www.ncbi.nlm.nih.gov/pubmed/34120588
http://dx.doi.org/10.1186/s12868-021-00647-y
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author Li, Peng
Xu, Jin
Gu, Huanhuan
Peng, Hua
Yin, You
Zhuang, Jianhua
author_facet Li, Peng
Xu, Jin
Gu, Huanhuan
Peng, Hua
Yin, You
Zhuang, Jianhua
author_sort Li, Peng
collection PubMed
description BACKGROUND: Memantine, a low- to moderate-affinity uncompetitive N-methyl-D-aspartate receptor antagonist, has been shown to improve cognitive functions in animal models of Alzheimer’s disease (AD). Here we treated APP/PS1 AD mice with a therapeutic dose of memantine (20 mg/kg/day) and examined its underlying mechanisms in ameliorating cognitive defects. METHODS: Using behavioral, electrophysiological, optogenetic and morphology approaches to explore how memantine delay the pathogenesis of AD. RESULTS: Memantine significantly improved the acquisition in Morris water maze (MWM) in APP/PS1 mice without affecting the speed of swimming. Furthermore, memantine enhanced EC to CA1 synaptic neurotransmission and promoted dendritic spine regeneration of EC neurons that projected to CA1. CONCLUSIONS: Our study reveals the underlying mechanism of memantine in the treatment of AD mice.
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spelling pubmed-82018112021-06-16 Memantine ameliorates cognitive deficit in AD mice via enhancement of entorhinal–CA1 projection Li, Peng Xu, Jin Gu, Huanhuan Peng, Hua Yin, You Zhuang, Jianhua BMC Neurosci Research BACKGROUND: Memantine, a low- to moderate-affinity uncompetitive N-methyl-D-aspartate receptor antagonist, has been shown to improve cognitive functions in animal models of Alzheimer’s disease (AD). Here we treated APP/PS1 AD mice with a therapeutic dose of memantine (20 mg/kg/day) and examined its underlying mechanisms in ameliorating cognitive defects. METHODS: Using behavioral, electrophysiological, optogenetic and morphology approaches to explore how memantine delay the pathogenesis of AD. RESULTS: Memantine significantly improved the acquisition in Morris water maze (MWM) in APP/PS1 mice without affecting the speed of swimming. Furthermore, memantine enhanced EC to CA1 synaptic neurotransmission and promoted dendritic spine regeneration of EC neurons that projected to CA1. CONCLUSIONS: Our study reveals the underlying mechanism of memantine in the treatment of AD mice. BioMed Central 2021-06-14 /pmc/articles/PMC8201811/ /pubmed/34120588 http://dx.doi.org/10.1186/s12868-021-00647-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Li, Peng
Xu, Jin
Gu, Huanhuan
Peng, Hua
Yin, You
Zhuang, Jianhua
Memantine ameliorates cognitive deficit in AD mice via enhancement of entorhinal–CA1 projection
title Memantine ameliorates cognitive deficit in AD mice via enhancement of entorhinal–CA1 projection
title_full Memantine ameliorates cognitive deficit in AD mice via enhancement of entorhinal–CA1 projection
title_fullStr Memantine ameliorates cognitive deficit in AD mice via enhancement of entorhinal–CA1 projection
title_full_unstemmed Memantine ameliorates cognitive deficit in AD mice via enhancement of entorhinal–CA1 projection
title_short Memantine ameliorates cognitive deficit in AD mice via enhancement of entorhinal–CA1 projection
title_sort memantine ameliorates cognitive deficit in ad mice via enhancement of entorhinal–ca1 projection
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201811/
https://www.ncbi.nlm.nih.gov/pubmed/34120588
http://dx.doi.org/10.1186/s12868-021-00647-y
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