دورية أكاديمية
Neuronal cholesterol synthesis is essential for repair of chronically demyelinated lesions in mice.
| العنوان: | Neuronal cholesterol synthesis is essential for repair of chronically demyelinated lesions in mice. |
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| المؤلفون: | Berghoff SA; Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany. Electronic address: berghoff@em.mpg.de., Spieth L; Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany., Sun T; Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany; Institute for Medical Systems Biology, Center for Molecular Neurobiology Hamburg, Hamburg, Germany., Hosang L; Institute for Neuroimmunology and Multiple Sclerosis Research, University Medical Center Göttingen, Göttingen, Germany., Depp C; Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany., Sasmita AO; Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany., Vasileva MH; Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany., Scholz P; Department of Plant Biochemistry, Albrecht-von-Haller-Institute for Plant Sciences and Göttingen Center for Molecular Biosciences (GZMB), University of Göttingen, Göttingen, Germany., Zhao Y; Institute for Medical Systems Biology, Center for Molecular Neurobiology Hamburg, Hamburg, Germany., Krueger-Burg D; Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany., Wichert S; Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany., Brown ER; School of Engineering and Physical Sciences, Institute of Biological Chemistry, Biophysics and Bioengineering, James Naysmith Building, Heriot Watt University, Edinburgh, UK., Michail K; School of Engineering and Physical Sciences, Institute of Biological Chemistry, Biophysics and Bioengineering, James Naysmith Building, Heriot Watt University, Edinburgh, UK., Nave KA; Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany., Bonn S; Institute for Medical Systems Biology, Center for Molecular Neurobiology Hamburg, Hamburg, Germany., Odoardi F; Institute for Neuroimmunology and Multiple Sclerosis Research, University Medical Center Göttingen, Göttingen, Germany., Rossner M; Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany., Ischebeck T; Department of Plant Biochemistry, Albrecht-von-Haller-Institute for Plant Sciences and Göttingen Center for Molecular Biosciences (GZMB), University of Göttingen, Göttingen, Germany; Service Unit for Metabolomics and Lipidomics, Göttingen Center for Molecular Biosciences (GZMB), University of Göttingen, Göttingen, Germany., Edgar JM; Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany; Axo-glial Group, Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK., Saher G; Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany. Electronic address: saher@em.mpg.de. |
| المصدر: | Cell reports [Cell Rep] 2021 Oct 26; Vol. 37 (4), pp. 109889. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
| مواضيع طبية MeSH: | Cholesterol*/biosynthesis , Cholesterol*/genetics , Multiple Sclerosis*/genetics , Multiple Sclerosis*/metabolism , Myelin Sheath*/genetics , Myelin Sheath*/metabolism, Oligodendrocyte Precursor Cells/*metabolism , Remyelination/*genetics, Animals ; Disease Models, Animal ; Humans ; Mice ; Mice, Knockout |
| مستخلص: | Astrocyte-derived cholesterol supports brain cells under physiological conditions. However, in demyelinating lesions, astrocytes downregulate cholesterol synthesis, and the cholesterol that is essential for remyelination has to originate from other cellular sources. Here, we show that repair following acute versus chronic demyelination involves distinct processes. In particular, in chronic myelin disease, when recycling of lipids is often defective, de novo neuronal cholesterol synthesis is critical for regeneration. By gene expression profiling, genetic loss-of-function experiments, and comprehensive phenotyping, we provide evidence that neurons increase cholesterol synthesis in chronic myelin disease models and in patients with multiple sclerosis (MS). In mouse models, neuronal cholesterol facilitates remyelination specifically by triggering oligodendrocyte precursor cell proliferation. Our data contribute to the understanding of disease progression and have implications for therapeutic strategies in patients with MS. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| معلومات مُعتمدة: | NC/L000423/1 United Kingdom NC3RS_ National Centre for the Replacement, Refinement and Reduction of Animals in Research |
| فهرسة مساهمة: | Keywords: EAE; OPC; cholesterol; cuprizone; demyelination; knockout; multiple sclerosis; myelin; neuron; oligodendrocyte |
| المشرفين على المادة: | 97C5T2UQ7J (Cholesterol) |
| تواريخ الأحداث: | Date Created: 20211027 Date Completed: 20220210 Latest Revision: 20230322 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.celrep.2021.109889 |
| PMID: | 34706227 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2211-1247 |
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| DOI: | 10.1016/j.celrep.2021.109889 |