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Dl-3-n-Butylphthalide Reduces Cognitive Deficits and Alleviates Neuropathology in P301S Tau Transgenic Mice
Alzheimer’s disease (AD) is a destructive and burdensome neurodegenerative disease, one of the most common characteristics of which are neurofibrillary tangles (NFTs) that are composed of abnormal tau protein. Animal studies have suggested that dl-3-n-butylphthalide (dl-NBP) alleviates cognitive imp...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902884/ https://www.ncbi.nlm.nih.gov/pubmed/33642981 http://dx.doi.org/10.3389/fnins.2021.620176 |
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author | Chang, Yanmin Yao, Yi Ma, Rong Wang, Zemin Hu, Junjie Wu, Yanqing Jiang, Xingjun Li, Lulu Li, Gang |
author_facet | Chang, Yanmin Yao, Yi Ma, Rong Wang, Zemin Hu, Junjie Wu, Yanqing Jiang, Xingjun Li, Lulu Li, Gang |
author_sort | Chang, Yanmin |
collection | PubMed |
description | Alzheimer’s disease (AD) is a destructive and burdensome neurodegenerative disease, one of the most common characteristics of which are neurofibrillary tangles (NFTs) that are composed of abnormal tau protein. Animal studies have suggested that dl-3-n-butylphthalide (dl-NBP) alleviates cognitive impairment in mouse models of APP/PS1 and SAMP8. However, the underlying mechanisms related to this remain unclear. In this study, we examined the effects of dl-NBP on learning and memory in P301S transgenic mice, which carry the human tau gene with the P301S mutation. We found that dl-NBP supplementation effectively improved behavioral deficits and rescued synaptic loss in P301S tau transgenic mice, compared with vehicle-treated P301S mice. Furthermore, we also found that it markedly inhibited the hyperphosphorylated tau at the Ser262 site and decreased the activity of MARK4, which was associated with tau at the Ser262 site. Finally, dl-NBP treatment exerted anti-inflammatory effects and reduced inflammatory responses in P301S mice. In conclusion, our results provide evidence that dl-NBP has a promising potential for the therapy of tauopathies, including AD. |
format | Online Article Text |
id | pubmed-7902884 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79028842021-02-25 Dl-3-n-Butylphthalide Reduces Cognitive Deficits and Alleviates Neuropathology in P301S Tau Transgenic Mice Chang, Yanmin Yao, Yi Ma, Rong Wang, Zemin Hu, Junjie Wu, Yanqing Jiang, Xingjun Li, Lulu Li, Gang Front Neurosci Neuroscience Alzheimer’s disease (AD) is a destructive and burdensome neurodegenerative disease, one of the most common characteristics of which are neurofibrillary tangles (NFTs) that are composed of abnormal tau protein. Animal studies have suggested that dl-3-n-butylphthalide (dl-NBP) alleviates cognitive impairment in mouse models of APP/PS1 and SAMP8. However, the underlying mechanisms related to this remain unclear. In this study, we examined the effects of dl-NBP on learning and memory in P301S transgenic mice, which carry the human tau gene with the P301S mutation. We found that dl-NBP supplementation effectively improved behavioral deficits and rescued synaptic loss in P301S tau transgenic mice, compared with vehicle-treated P301S mice. Furthermore, we also found that it markedly inhibited the hyperphosphorylated tau at the Ser262 site and decreased the activity of MARK4, which was associated with tau at the Ser262 site. Finally, dl-NBP treatment exerted anti-inflammatory effects and reduced inflammatory responses in P301S mice. In conclusion, our results provide evidence that dl-NBP has a promising potential for the therapy of tauopathies, including AD. Frontiers Media S.A. 2021-02-10 /pmc/articles/PMC7902884/ /pubmed/33642981 http://dx.doi.org/10.3389/fnins.2021.620176 Text en Copyright © 2021 Chang, Yao, Ma, Wang, Hu, Wu, Jiang, Li and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Chang, Yanmin Yao, Yi Ma, Rong Wang, Zemin Hu, Junjie Wu, Yanqing Jiang, Xingjun Li, Lulu Li, Gang Dl-3-n-Butylphthalide Reduces Cognitive Deficits and Alleviates Neuropathology in P301S Tau Transgenic Mice |
title | Dl-3-n-Butylphthalide Reduces Cognitive Deficits and Alleviates Neuropathology in P301S Tau Transgenic Mice |
title_full | Dl-3-n-Butylphthalide Reduces Cognitive Deficits and Alleviates Neuropathology in P301S Tau Transgenic Mice |
title_fullStr | Dl-3-n-Butylphthalide Reduces Cognitive Deficits and Alleviates Neuropathology in P301S Tau Transgenic Mice |
title_full_unstemmed | Dl-3-n-Butylphthalide Reduces Cognitive Deficits and Alleviates Neuropathology in P301S Tau Transgenic Mice |
title_short | Dl-3-n-Butylphthalide Reduces Cognitive Deficits and Alleviates Neuropathology in P301S Tau Transgenic Mice |
title_sort | dl-3-n-butylphthalide reduces cognitive deficits and alleviates neuropathology in p301s tau transgenic mice |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902884/ https://www.ncbi.nlm.nih.gov/pubmed/33642981 http://dx.doi.org/10.3389/fnins.2021.620176 |
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