GDNF-enhanced axonal regeneration and myelination following spinal cord injury is mediated by primary effects on neurons

Liqun Zhang, Zhengwen Ma, George M. Smith, Xuejun Wen, Yelena Pressman, Patrick M. Wood, Xiao Ming Xu

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

We previously demonstrated that coadministration of glial cell line-derived neurotrophic factor (GDNF) with grafts of Schwann cells (SCs) enhanced axonal regeneration and remyelination following spinal cord injury (SCI). However, the cellular target through which GDNF mediates such actions was unclear. Here, we report that GDNF enhanced both the number and caliber of regenerated axons in vivo and increased neurite outgrowth of dorsal root ganglion neurons (DRGN) in vitro, suggesting that GDNF has a direct effect on neurons. In SC-DRGN coculture, GDNF significantly increased the number of myelin sheaths produced by SCs. GDNF treatment had no effect on the proliferation of isolated SCs but enhanced the proliferation of SCs already in contact with axons. GDNF increased the expression of the 140 kDa neural cell adhesion molecule (NCAM) in isolated SCs but not their expression of the adhesion molecule L1 or the secretion of the neurotrophins NGF, NT3, or BDNF. Overall, these results support the hypothesis that GDNF-enhanced axonal regeneration and SC myelination is mediated mainly through a direct effect of GDNF on neurons. They also suggest that the combination of GDNF administration and SC transplantation may represent an effective strategy to promote axonal regeneration and myelin formation after injury in the spinal cord.

Original languageEnglish (US)
Pages (from-to)1178-1191
Number of pages14
JournalGlia
Volume57
Issue number11
DOIs
StatePublished - Aug 15 2009

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Keywords

  • Axon
  • GDNF
  • Myelination
  • Regeneration
  • Schwann cell
  • Spinal cord injury

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

Zhang, L., Ma, Z., Smith, G. M., Wen, X., Pressman, Y., Wood, P. M., & Xu, X. M. (2009). GDNF-enhanced axonal regeneration and myelination following spinal cord injury is mediated by primary effects on neurons. Glia, 57(11), 1178-1191. https://doi.org/10.1002/glia.20840