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

Yuan-Yuan Xie; Yuan-Yuan Xie; Yuan-Yuan Xie; Ting-Ting Pan; Ting-Ting Pan; De-en Xu; Xin Huang; Xin Huang; Xin Huang; Yong Tang; Yong Tang; Wenhui Huang; Rui Chen; Li Lu; Hao Chi; Hao Chi; Quan-Hong Ma; Quan-Hong Ma

doi:10.3389/fcell.2021.733945

Frontiers in Cell and Developmental Biology (Oct 2021)

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

Yuan-Yuan Xie,
Yuan-Yuan Xie,
Yuan-Yuan Xie,
Ting-Ting Pan,
Ting-Ting Pan,
De-en Xu,
Xin Huang,
Xin Huang,
Xin Huang,
Yong Tang,
Yong Tang,
Wenhui Huang,
Rui Chen,
Li Lu,
Hao Chi,
Hao Chi,
Quan-Hong Ma,
Quan-Hong Ma

Affiliations

Yuan-Yuan Xie: Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
Yuan-Yuan Xie: Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Soochow University, Suzhou, China
Yuan-Yuan Xie: Department of Anatomy, Shanxi Medical University, Taiyuan, China
Ting-Ting Pan: Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
Ting-Ting Pan: Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Soochow University, Suzhou, China
De-en Xu: Wuxi No. 2 People’s Hospital, Wuxi, China
Xin Huang: Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
Xin Huang: Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Soochow University, Suzhou, China
Xin Huang: Department of Anatomy, Shanxi Medical University, Taiyuan, China
Yong Tang: International Collaborative Centre on Big Science Plan for Purinergic Signaling, Chengdu University of Traditional Chinese Medicine, Chengdu, China
Yong Tang: Acupuncture and Chronobiology Key Laboratory of Sichuan Province, Chengdu, China
Wenhui Huang: Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of Saarland, Homburg, Germany
Rui Chen: Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
Li Lu: Department of Anatomy, Shanxi Medical University, Taiyuan, China
Hao Chi: Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
Hao Chi: Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Soochow University, Suzhou, China
Quan-Hong Ma: Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
Quan-Hong Ma: Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Soochow University, Suzhou, China

DOI: https://doi.org/10.3389/fcell.2021.733945
Journal volume & issue: Vol. 9

Abstract

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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.

Published in Frontiers in Cell and Developmental Biology

ISSN: 2296-634X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: https://www.frontiersin.org/journals/cell-and-developmental-biology

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