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Dietary cholesterol promotes repair of demyelinated lesions in the adult brain

Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is u...

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Autores principales: Berghoff, Stefan A., Gerndt, Nina, Winchenbach, Jan, Stumpf, Sina K., Hosang, Leon, Odoardi, Francesca, Ruhwedel, Torben, Böhler, Carolin, Barrette, Benoit, Stassart, Ruth, Liebetanz, David, Dibaj, Payam, Möbius, Wiebke, Edgar, Julia M., Saher, Gesine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286209/
https://www.ncbi.nlm.nih.gov/pubmed/28117328
http://dx.doi.org/10.1038/ncomms14241
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author Berghoff, Stefan A.
Gerndt, Nina
Winchenbach, Jan
Stumpf, Sina K.
Hosang, Leon
Odoardi, Francesca
Ruhwedel, Torben
Böhler, Carolin
Barrette, Benoit
Stassart, Ruth
Liebetanz, David
Dibaj, Payam
Möbius, Wiebke
Edgar, Julia M.
Saher, Gesine
author_facet Berghoff, Stefan A.
Gerndt, Nina
Winchenbach, Jan
Stumpf, Sina K.
Hosang, Leon
Odoardi, Francesca
Ruhwedel, Torben
Böhler, Carolin
Barrette, Benoit
Stassart, Ruth
Liebetanz, David
Dibaj, Payam
Möbius, Wiebke
Edgar, Julia M.
Saher, Gesine
author_sort Berghoff, Stefan A.
collection PubMed
description Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol. Concomitant with blood-brain barrier impairment, supplemented cholesterol directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning. Remarkably, in experimental autoimmune encephalomyelitis, cholesterol supplementation does not exacerbate disease expression. These findings emphasize the safety of dietary cholesterol in inflammatory diseases and point to a previously unrecognized role of cholesterol in promoting repair after demyelinating episodes.
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spelling pubmed-52862092017-02-22 Dietary cholesterol promotes repair of demyelinated lesions in the adult brain Berghoff, Stefan A. Gerndt, Nina Winchenbach, Jan Stumpf, Sina K. Hosang, Leon Odoardi, Francesca Ruhwedel, Torben Böhler, Carolin Barrette, Benoit Stassart, Ruth Liebetanz, David Dibaj, Payam Möbius, Wiebke Edgar, Julia M. Saher, Gesine Nat Commun Article Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol. Concomitant with blood-brain barrier impairment, supplemented cholesterol directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning. Remarkably, in experimental autoimmune encephalomyelitis, cholesterol supplementation does not exacerbate disease expression. These findings emphasize the safety of dietary cholesterol in inflammatory diseases and point to a previously unrecognized role of cholesterol in promoting repair after demyelinating episodes. Nature Publishing Group 2017-01-24 /pmc/articles/PMC5286209/ /pubmed/28117328 http://dx.doi.org/10.1038/ncomms14241 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Berghoff, Stefan A.
Gerndt, Nina
Winchenbach, Jan
Stumpf, Sina K.
Hosang, Leon
Odoardi, Francesca
Ruhwedel, Torben
Böhler, Carolin
Barrette, Benoit
Stassart, Ruth
Liebetanz, David
Dibaj, Payam
Möbius, Wiebke
Edgar, Julia M.
Saher, Gesine
Dietary cholesterol promotes repair of demyelinated lesions in the adult brain
title Dietary cholesterol promotes repair of demyelinated lesions in the adult brain
title_full Dietary cholesterol promotes repair of demyelinated lesions in the adult brain
title_fullStr Dietary cholesterol promotes repair of demyelinated lesions in the adult brain
title_full_unstemmed Dietary cholesterol promotes repair of demyelinated lesions in the adult brain
title_short Dietary cholesterol promotes repair of demyelinated lesions in the adult brain
title_sort dietary cholesterol promotes repair of demyelinated lesions in the adult brain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286209/
https://www.ncbi.nlm.nih.gov/pubmed/28117328
http://dx.doi.org/10.1038/ncomms14241
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