The response of neuromuscular junctions to injury is developmentally regulated

Lyndsay M. Murray, Laura H. Comley, Thomas H. Gillingwater, Simon H. Parson*

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

It is well established that developmental maturity is a key factor regulating the response of lower motor neurons to injury. The influence of age on the survival of motor neuron cell somata following axotomy is well documented, but it remains unclear whether maturity also influences the degeneration of axonal and synaptic compartments at the neuromuscular junction. Such information is important for our interpretation of data suggesting that neonatal neuromuscular junctions are particularly vulnerable in neurodegenerative conditions that affect the developing postnatal nervous system, such as spinal muscular atrophy. Here, we have examined the role of development in regulating the vulnerability of mouse neuromuscular junctions to two mechanistically distinct degenerative insults: hypoxia and peripheral nerve injury. We report that neuromuscular junctions in neonatal mice are significantly more resistant to both hypoxia and nerve injury than those in adult mice, with a transition from the neonatal to adult phenotype occurring at 2-3 wk of age. We also demonstrate that the reduced vulnerability of neuromuscular junctions observed in neonatal mice is not determined by the maturity of the synapse per se, suggesting that properties associated with the neonatal environment and/or age of the neuron are responsible for modulating vulnerability. Our results are in stark contrast to previous studies showing that motor neuron cell somata are markedly more vulnerable to axotomy in neonatal mice. We conclude that neonatal neuromuscular junctions are resistant to a range of neurodegenerative insults in vivo and that this resistance is developmentally regulated.-Murray, L. M., Comley, L. H., Gillingwater, T. H., Parson, S. H. The response of neuromuscular junctions to injury is developmentally regulated. FASEB J. 25, 1306-1313 (2011). www.fasebj.org

Original languageEnglish
Pages (from-to)1306-1313
Number of pages8
JournalThe FASEB Journal
Volume25
Issue number4
Early online date12 Jan 2011
DOIs
Publication statusPublished - Apr 2011

Keywords

  • hypoxia
  • vulnerability
  • motor neuron
  • Wallerian degeneration
  • spinal muscular-atrophy
  • affinity neurotrophin receptor
  • amyotrophic-lateral-sclerosis
  • Guillain-Barre-syndrome
  • Schwann-cell apoptosis
  • motor-nerve terminals
  • selective vulnerability
  • synaptic vulnerability
  • motoneuron death

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