SnoN facilitates axonal regeneration after spinal cord injury

PLoS One. 2013 Aug 2;8(8):e71906. doi: 10.1371/journal.pone.0071906. Print 2013.

Abstract

Adult CNS neurons exhibit a reduced capacity for growth compared to developing neurons, due in part to downregulation of growth-associated genes as development is completed. We tested the hypothesis that SnoN, an embryonically regulated transcription factor that specifies growth of the axonal compartment, can enhance growth in injured adult neurons. In vitro, SnoN overexpression in dissociated adult DRG neuronal cultures significantly enhanced neurite outgrowth. Moreover, TGF-β1, a negative regulator of SnoN, inhibited neurite outgrowth, and SnoN over-expression overcame this inhibition. We then examined whether SnoN influenced axonal regeneration in vivo: indeed, expression of a mutant form of SnoN resistant to degradation significantly enhanced axonal regeneration following cervical spinal cord injury, despite peri-lesional upregulation of TGF-β1. Thus, a developmental mechanism that specifies extension of the axonal compartment also promotes axonal regeneration after adult CNS injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Axons / physiology*
  • Cells, Cultured
  • Female
  • Ganglia, Spinal / growth & development
  • Ganglia, Spinal / injuries
  • Ganglia, Spinal / metabolism
  • Immunoblotting
  • Nerve Regeneration / physiology*
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism
  • Neurons / pathology*
  • Rats
  • Rats, Inbred F344
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / pathology*
  • Transcription Factors / metabolism*
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Nerve Tissue Proteins
  • Skil_v1 protein, rat
  • Transcription Factors
  • Transforming Growth Factor beta1