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Clemastine Ameliorates Myelin Deficits via Preventing Senescence of Oligodendrocytes Precursor Cells in Alzheimer’s Disease Model Mouse

Disrupted myelin and impaired myelin repair have been observed in the brains of patients and various mouse models of Alzheimer’s disease (AD). Clemastine, an H1-antihistamine, shows the capability to induce oligodendrocyte precursor cell (OPC) differentiation and myelin formation under different neu...

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Autores principales: Xie, Yuan-Yuan, Pan, Ting-Ting, Xu, De-en, Huang, Xin, Tang, Yong, Huang, Wenhui, Chen, Rui, Lu, Li, Chi, Hao, Ma, Quan-Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567029/
https://www.ncbi.nlm.nih.gov/pubmed/34746130
http://dx.doi.org/10.3389/fcell.2021.733945
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author Xie, Yuan-Yuan
Pan, Ting-Ting
Xu, De-en
Huang, Xin
Tang, Yong
Huang, Wenhui
Chen, Rui
Lu, Li
Chi, Hao
Ma, Quan-Hong
author_facet Xie, Yuan-Yuan
Pan, Ting-Ting
Xu, De-en
Huang, Xin
Tang, Yong
Huang, Wenhui
Chen, Rui
Lu, Li
Chi, Hao
Ma, Quan-Hong
author_sort Xie, Yuan-Yuan
collection PubMed
description Disrupted myelin and impaired myelin repair have been observed in the brains of patients and various mouse models of Alzheimer’s disease (AD). Clemastine, an H1-antihistamine, shows the capability to induce oligodendrocyte precursor cell (OPC) differentiation and myelin formation under different neuropathological conditions featuring demyelination via the antagonism of M1 muscarinic receptor. In this study, we investigated if aged APPSwe/PS1dE9 mice, a model of AD, can benefit from chronic clemastine treatment. We found the treatment reduced brain amyloid-beta deposition and rescued the short-term memory deficit of the mice. The densities of OPCs, oligodendrocytes, and myelin were enhanced upon the treatment, whereas the levels of degraded MBP were reduced, a marker for degenerated myelin. In addition, we also suggest the role of clemastine in preventing OPCs from entering the state of cellular senescence, which was shown recently as an essential causal factor in AD pathogenesis. Thus, clemastine exhibits therapeutic potential in AD via preventing senescence of OPCs.
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spelling pubmed-85670292021-11-05 Clemastine Ameliorates Myelin Deficits via Preventing Senescence of Oligodendrocytes Precursor Cells in Alzheimer’s Disease Model Mouse Xie, Yuan-Yuan Pan, Ting-Ting Xu, De-en Huang, Xin Tang, Yong Huang, Wenhui Chen, Rui Lu, Li Chi, Hao Ma, Quan-Hong Front Cell Dev Biol Cell and Developmental Biology Disrupted myelin and impaired myelin repair have been observed in the brains of patients and various mouse models of Alzheimer’s disease (AD). Clemastine, an H1-antihistamine, shows the capability to induce oligodendrocyte precursor cell (OPC) differentiation and myelin formation under different neuropathological conditions featuring demyelination via the antagonism of M1 muscarinic receptor. In this study, we investigated if aged APPSwe/PS1dE9 mice, a model of AD, can benefit from chronic clemastine treatment. We found the treatment reduced brain amyloid-beta deposition and rescued the short-term memory deficit of the mice. The densities of OPCs, oligodendrocytes, and myelin were enhanced upon the treatment, whereas the levels of degraded MBP were reduced, a marker for degenerated myelin. In addition, we also suggest the role of clemastine in preventing OPCs from entering the state of cellular senescence, which was shown recently as an essential causal factor in AD pathogenesis. Thus, clemastine exhibits therapeutic potential in AD via preventing senescence of OPCs. Frontiers Media S.A. 2021-10-21 /pmc/articles/PMC8567029/ /pubmed/34746130 http://dx.doi.org/10.3389/fcell.2021.733945 Text en Copyright © 2021 Xie, Pan, Xu, Huang, Tang, Huang, Chen, Lu, Chi and Ma. 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 Cell and Developmental Biology
Xie, Yuan-Yuan
Pan, Ting-Ting
Xu, De-en
Huang, Xin
Tang, Yong
Huang, Wenhui
Chen, Rui
Lu, Li
Chi, Hao
Ma, Quan-Hong
Clemastine Ameliorates Myelin Deficits via Preventing Senescence of Oligodendrocytes Precursor Cells in Alzheimer’s Disease Model Mouse
title Clemastine Ameliorates Myelin Deficits via Preventing Senescence of Oligodendrocytes Precursor Cells in Alzheimer’s Disease Model Mouse
title_full Clemastine Ameliorates Myelin Deficits via Preventing Senescence of Oligodendrocytes Precursor Cells in Alzheimer’s Disease Model Mouse
title_fullStr Clemastine Ameliorates Myelin Deficits via Preventing Senescence of Oligodendrocytes Precursor Cells in Alzheimer’s Disease Model Mouse
title_full_unstemmed Clemastine Ameliorates Myelin Deficits via Preventing Senescence of Oligodendrocytes Precursor Cells in Alzheimer’s Disease Model Mouse
title_short Clemastine Ameliorates Myelin Deficits via Preventing Senescence of Oligodendrocytes Precursor Cells in Alzheimer’s Disease Model Mouse
title_sort clemastine ameliorates myelin deficits via preventing senescence of oligodendrocytes precursor cells in alzheimer’s disease model mouse
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567029/
https://www.ncbi.nlm.nih.gov/pubmed/34746130
http://dx.doi.org/10.3389/fcell.2021.733945
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