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The role of oligodendrocyte remyelination in locomotor recovery after traumatic spinal cord injury Manesh, Sohrab
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 precursor cells (OPCs) in mice prior to SCI. While OPC proliferation and density were not altered by Myrf inducible knockout after SCI, the accumulation of new oligodendrocytes was prevented. This greatly inhibited myelin regeneration resulting in a loss of myelinated axons at the lesion epicenter. However, spontaneous locomotor recovery after SCI was not altered by remyelination failure. In controls with functional MYRF, locomotor recovery preceded the onset of substantial oligodendrocyte myelin regeneration. We next assessed locomotor recovery in a severe model of SCI where fewer axons were spared. Here animals were still able to recover despite the inhibition of remyelination. We noticed that ion channels were redistributed in demyelinated axons. Further testing showed knockout animals were able to show conduction properties similar to that of control animals. Collectively, these data demonstrate that MYRF expression in PDGFRα-positive cell derived oligodendrocytes is indispensable for oligodendrocyte myelin regeneration following contusive SCI, that remyelination is not required for spontaneous recovery of stepping in moderate or severe injuries, and that demyelinated axons redistribute voltage gated ion channels and conduction properties similar to that of unmyelinated axons.
Item Metadata
Title |
The role of oligodendrocyte remyelination in locomotor recovery after traumatic spinal cord injury
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2020
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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 precursor cells (OPCs) in mice prior to SCI. While OPC
proliferation and density were not altered by Myrf inducible knockout after SCI, the
accumulation of new oligodendrocytes was prevented. This greatly inhibited myelin regeneration
resulting in a loss of myelinated axons at the lesion epicenter. However, spontaneous locomotor
recovery after SCI was not altered by remyelination failure. In controls with functional MYRF,
locomotor recovery preceded the onset of substantial oligodendrocyte myelin regeneration. We
next assessed locomotor recovery in a severe model of SCI where fewer axons were spared. Here
animals were still able to recover despite the inhibition of remyelination. We noticed that ion
channels were redistributed in demyelinated axons. Further testing showed knockout animals
were able to show conduction properties similar to that of control animals. Collectively, these
data demonstrate that MYRF expression in PDGFRα-positive cell derived oligodendrocytes is
indispensable for oligodendrocyte myelin regeneration following contusive SCI, that
remyelination is not required for spontaneous recovery of stepping in moderate or severe
injuries, and that demyelinated axons redistribute voltage gated ion channels and conduction
properties similar to that of unmyelinated axons.
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Genre | |
Type | |
Language |
eng
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Date Available |
2021-10-31
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
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DOI |
10.14288/1.0394835
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2020-11
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Campus | |
Scholarly Level |
Graduate
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Rights URI | |
Aggregated Source Repository |
DSpace
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Rights
Attribution-NonCommercial-NoDerivatives 4.0 International