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

Greg J Duncan; Sohrab B Manesh; Brett J Hilton; Peggy Assinck; Jie Liu; Aaron Moulson; Jason R Plemel; Wolfram Tetzlaff

doi:10.1038/s41467-018-05473-1

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

Greg J Duncan, Sohrab B Manesh, Brett J Hilton, Peggy Assinck, Jie Liu, Aaron Moulson, Jason R Plemel, Wolfram Tetzlaff

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Article number	3066
Number of pages	16
Journal	Nature Communications
Volume	9
DOIs	https://doi.org/10.1038/s41467-018-05473-1
Publication status	Published - 3 Aug 2018

Keywords / Materials (for Non-textual outputs)

Animals
Axons/metabolism
Behavior, Animal
Cell Differentiation
Cell Proliferation
Disease Models, Animal
Female
Gene Deletion
Male
Mice
Mice, Knockout
Myelin Sheath/metabolism
Nerve Regeneration/physiology
Neural Stem Cells/pathology
Oligodendroglia/metabolism
Receptor, Platelet-Derived Growth Factor alpha
Remyelination/physiology
Spinal Cord/metabolism
Spinal Cord Injuries/metabolism
Transcription Factors/genetics

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Assinck P Locomotor recovery..
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Final published version, 11.3 MBLicence: Creative Commons: Attribution (CC-BY)

Cite this

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title = "Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination",

abstract = "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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author = "Duncan, {Greg J} and Manesh, {Sohrab B} and Hilton, {Brett J} and Peggy Assinck and Jie Liu and Aaron Moulson and Plemel, {Jason R} and Wolfram Tetzlaff",

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doi = "10.1038/s41467-018-05473-1",

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AU - Assinck, Peggy

AU - Liu, Jie

AU - Moulson, Aaron

AU - Plemel, Jason R

AU - Tetzlaff, Wolfram

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N2 - 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.

AB - 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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KW - Cell Proliferation

KW - Disease Models, Animal

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KW - Mice

KW - Mice, Knockout

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

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

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