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

Nat Commun. 2018 Aug 3;9(1):3066. doi: 10.1038/s41467-018-05473-1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Axons / pathology
  • 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*
  • Oligodendroglia / pathology
  • Receptor, Platelet-Derived Growth Factor alpha
  • Remyelination / physiology*
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / pathology*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*

Substances

  • Transcription Factors
  • myelin gene regulatory factor, mouse
  • Receptor, Platelet-Derived Growth Factor alpha