Schwann cell apoptosis in the postnatal axotomized sciatic nerve is mediated via NGF through the low-affinity neurotrophin receptor

Steven Petratos, Helmut Butzkueven, Kylie Shipham, Helen Cooper, Tamara Bucci, Kate Reid, Elizabeth Lopes, Ben Emery, Surindar S. Cheema, Trevor J. Kilpatrick

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Schwann cell death is a developmentally regulated phenomenon and is also induced after peripheral nerve axotomy in neonatal rodents. In this study, we explored whether ligand-induced activation of the low-affinity neurotrophin receptor (p75NTR) is responsible for inducing Schwann cell death in vivo. Administration of exogenous nerve growth factor (NGF) to the axotomized nerve site in wild-type animals resulted in a 2.6-fold increase in Schwann cell apoptosis in the distal nerve stumps compared to axotomy alone. No increase in apoptosis, above baseline levels, was seen in p75NTR-mutant mice either with or without NGF. When anti-NGF antibodies were administered to the site of the peripheral nerve lesion in wild-type mice there was a reduction in the percentage of Schwann cell apoptosis to levels seen in both the quiescent state and in the axotomized nerves of the p75NTR-mutant mice. These results demonstrate that apoptosis of Schwann cells in axotomized peripheral nerve is mediated predominantly through p75NTR signaling and initiated via endogenously produced NGF.

Original languageEnglish (US)
Pages (from-to)398-411
Number of pages14
JournalJournal of Neuropathology and Experimental Neurology
Volume62
Issue number4
DOIs
StatePublished - Apr 1 2003

Keywords

  • Apoptosis
  • Axotomy
  • Low-affinity neurotrophin receptor (p75NTR)
  • Nerve growth factor
  • Schwann cell

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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