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Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination

Remyelination occurs after spinal cord injury (SCI) but its functional relevance is unclear. We assessed the necessity of myelin regulatory factor (Myrf) in remyelination after contusive SCI by deleting the gene from platelet-derived growth factor receptor alpha positive (PDGFRα-positive) oligodendr...

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Autores principales: Duncan, Greg J., Manesh, Sohrab B., Hilton, Brett J., Assinck, Peggy, Liu, Jie, Moulson, Aaron, Plemel, Jason R., Tetzlaff, Wolfram
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076268/
https://www.ncbi.nlm.nih.gov/pubmed/30076300
http://dx.doi.org/10.1038/s41467-018-05473-1
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author Duncan, Greg J.
Manesh, Sohrab B.
Hilton, Brett J.
Assinck, Peggy
Liu, Jie
Moulson, Aaron
Plemel, Jason R.
Tetzlaff, Wolfram
author_facet Duncan, Greg J.
Manesh, Sohrab B.
Hilton, Brett J.
Assinck, Peggy
Liu, Jie
Moulson, Aaron
Plemel, Jason R.
Tetzlaff, Wolfram
author_sort Duncan, Greg J.
collection PubMed
description Remyelination occurs after spinal cord injury (SCI) but its functional relevance is unclear. We assessed the necessity of myelin regulatory factor (Myrf) in remyelination after contusive SCI by deleting the gene from platelet-derived growth factor receptor alpha positive (PDGFRα-positive) oligodendrocyte progenitor cells (OPCs) in mice prior to SCI. While OPC proliferation and density are not altered by Myrf inducible knockout after SCI, the accumulation of new oligodendrocytes is largely prevented. This greatly inhibits myelin regeneration, resulting in a 44% reduction in myelinated axons at the lesion epicenter. However, spontaneous locomotor recovery after SCI is not altered by remyelination failure. In controls with functional MYRF, locomotor recovery precedes the onset of most oligodendrocyte myelin regeneration. Collectively, these data demonstrate that MYRF expression in PDGFRα-positive cell derived oligodendrocytes is indispensable for myelin regeneration following contusive SCI but that oligodendrocyte remyelination is not required for spontaneous recovery of stepping.
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spelling pubmed-60762682018-08-07 Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination Duncan, Greg J. Manesh, Sohrab B. Hilton, Brett J. Assinck, Peggy Liu, Jie Moulson, Aaron Plemel, Jason R. Tetzlaff, Wolfram Nat Commun Article Remyelination occurs after spinal cord injury (SCI) but its functional relevance is unclear. We assessed the necessity of myelin regulatory factor (Myrf) in remyelination after contusive SCI by deleting the gene from platelet-derived growth factor receptor alpha positive (PDGFRα-positive) oligodendrocyte progenitor cells (OPCs) in mice prior to SCI. While OPC proliferation and density are not altered by Myrf inducible knockout after SCI, the accumulation of new oligodendrocytes is largely prevented. This greatly inhibits myelin regeneration, resulting in a 44% reduction in myelinated axons at the lesion epicenter. However, spontaneous locomotor recovery after SCI is not altered by remyelination failure. In controls with functional MYRF, locomotor recovery precedes the onset of most oligodendrocyte myelin regeneration. Collectively, these data demonstrate that MYRF expression in PDGFRα-positive cell derived oligodendrocytes is indispensable for myelin regeneration following contusive SCI but that oligodendrocyte remyelination is not required for spontaneous recovery of stepping. Nature Publishing Group UK 2018-08-03 /pmc/articles/PMC6076268/ /pubmed/30076300 http://dx.doi.org/10.1038/s41467-018-05473-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Duncan, Greg J.
Manesh, Sohrab B.
Hilton, Brett J.
Assinck, Peggy
Liu, Jie
Moulson, Aaron
Plemel, Jason R.
Tetzlaff, Wolfram
Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination
title Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination
title_full Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination
title_fullStr Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination
title_full_unstemmed Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination
title_short Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination
title_sort locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076268/
https://www.ncbi.nlm.nih.gov/pubmed/30076300
http://dx.doi.org/10.1038/s41467-018-05473-1
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