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Concomitant memantine and Lactobacillus plantarum treatment attenuates cognitive impairments in APP/PS1 mice
Trimethylamine-N-oxide (TMAO) is a gut microbial metabolite that promotes Alzheimer’s disease (AD) progression. Given that probiotics can alleviate AD symptoms by inhibiting the synthesis of TMAO, here we investigated the correlation between TMAO and cognitive deterioration by measuring TMAO levels...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977692/ https://www.ncbi.nlm.nih.gov/pubmed/31907339 http://dx.doi.org/10.18632/aging.102645 |
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author | Wang, Qiu-Jun Shen, Yue-E Wang, Xin Fu, Shuang Zhang, Xin Zhang, Yi-Na Wang, Rui-Tao |
author_facet | Wang, Qiu-Jun Shen, Yue-E Wang, Xin Fu, Shuang Zhang, Xin Zhang, Yi-Na Wang, Rui-Tao |
author_sort | Wang, Qiu-Jun |
collection | PubMed |
description | Trimethylamine-N-oxide (TMAO) is a gut microbial metabolite that promotes Alzheimer’s disease (AD) progression. Given that probiotics can alleviate AD symptoms by inhibiting the synthesis of TMAO, here we investigated the correlation between TMAO and cognitive deterioration by measuring TMAO levels in the plasma of choline-treated APP/PS1 mice (an AD mouse model) with and without probiotic treatments. We found that declines in L. plantarum in the gut were associated with cognitive impairment. Moreover, 12-weeks of treatment with memantine plus L. plantarum ameliorated cognitive deterioration, decreased Αβ levels in the hippocampus, and protected neuronal integrity and plasticity. These effects were accompanied by reductions in TMAO synthesis and neuroinflammation. These experiments demonstrate that L. plantarum augments the beneficial therapeutic effects of memantine treatment in APP/PS1 mice by remodeling the intestinal microbiota, inhibiting the synthesis of TMAO, and reducing clusterin levels. Our results thus highlight intestinal microbiota as a potential therapeutic target to decrease the risk of AD. |
format | Online Article Text |
id | pubmed-6977692 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-69776922020-01-31 Concomitant memantine and Lactobacillus plantarum treatment attenuates cognitive impairments in APP/PS1 mice Wang, Qiu-Jun Shen, Yue-E Wang, Xin Fu, Shuang Zhang, Xin Zhang, Yi-Na Wang, Rui-Tao Aging (Albany NY) Research Paper Trimethylamine-N-oxide (TMAO) is a gut microbial metabolite that promotes Alzheimer’s disease (AD) progression. Given that probiotics can alleviate AD symptoms by inhibiting the synthesis of TMAO, here we investigated the correlation between TMAO and cognitive deterioration by measuring TMAO levels in the plasma of choline-treated APP/PS1 mice (an AD mouse model) with and without probiotic treatments. We found that declines in L. plantarum in the gut were associated with cognitive impairment. Moreover, 12-weeks of treatment with memantine plus L. plantarum ameliorated cognitive deterioration, decreased Αβ levels in the hippocampus, and protected neuronal integrity and plasticity. These effects were accompanied by reductions in TMAO synthesis and neuroinflammation. These experiments demonstrate that L. plantarum augments the beneficial therapeutic effects of memantine treatment in APP/PS1 mice by remodeling the intestinal microbiota, inhibiting the synthesis of TMAO, and reducing clusterin levels. Our results thus highlight intestinal microbiota as a potential therapeutic target to decrease the risk of AD. Impact Journals 2020-01-06 /pmc/articles/PMC6977692/ /pubmed/31907339 http://dx.doi.org/10.18632/aging.102645 Text en Copyright © 2020 Wang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Wang, Qiu-Jun Shen, Yue-E Wang, Xin Fu, Shuang Zhang, Xin Zhang, Yi-Na Wang, Rui-Tao Concomitant memantine and Lactobacillus plantarum treatment attenuates cognitive impairments in APP/PS1 mice |
title | Concomitant memantine and Lactobacillus plantarum treatment attenuates cognitive impairments in APP/PS1 mice |
title_full | Concomitant memantine and Lactobacillus plantarum treatment attenuates cognitive impairments in APP/PS1 mice |
title_fullStr | Concomitant memantine and Lactobacillus plantarum treatment attenuates cognitive impairments in APP/PS1 mice |
title_full_unstemmed | Concomitant memantine and Lactobacillus plantarum treatment attenuates cognitive impairments in APP/PS1 mice |
title_short | Concomitant memantine and Lactobacillus plantarum treatment attenuates cognitive impairments in APP/PS1 mice |
title_sort | concomitant memantine and lactobacillus plantarum treatment attenuates cognitive impairments in app/ps1 mice |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977692/ https://www.ncbi.nlm.nih.gov/pubmed/31907339 http://dx.doi.org/10.18632/aging.102645 |
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