The neuroprotective factor Wlds fails to mitigate distal axonal and neuromuscular junction (NMJ) defects in mouse models of spinal muscular atrophy

Shingo Kariya, Rina Mauricio, Ya Dai, Umrao R. Monani

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Spinal muscular atrophy (SMA) is a common autosomal recessive neurodegenerative disorder in humans. Amongst the earliest signs of neurodegeneration are severe and progressive defects of the neuromuscular synapse. These defects, characterized by poor terminal arborization and immature motor endplates, presumably result in a loss of functional synapses. The slow Wallerian degeneration (Wlds) mutation in rodents has been shown to have a protective effect on mouse models of motor neuron disease by retarding axonal die-back and preventing neuromuscular synapse loss. In this study we tested the effects of the Wlds mutation on the disease phenotype of SMA model mice. Consistent with previous reports, the mutation slows axon and neuromuscular synapse loss following nerve injury in wild-type as well as in SMA mice. However, the synaptic defects found in severely affected SMA patients and model mice persist in the double (Wlds;SMA) mutants. No delay in disease onset was observed and survival was not significantly altered. Finally, Wlds had no effect on the striking phrenic nerve projection defects that we discovered in SMA model mice. Our results indicate that the reported protective effects of Wlds are insufficient to mitigate the neuromuscular phenotype due to reduced SMN protein, and that the mechanisms responsible for distal defects of the motor unit in SMA are unlikely to be similar to those causing neurodegeneration in genetic mutants such as the pmn mouse which is partially rescued by the Wlds protein.

Original languageEnglish (US)
Pages (from-to)246-251
Number of pages6
JournalNeuroscience letters
Volume449
Issue number3
DOIs
StatePublished - Jan 16 2009
Externally publishedYes

Keywords

  • Neuromuscular junctions
  • Spinal muscular atrophy
  • Wallerian degeneration

ASJC Scopus subject areas

  • Neuroscience(all)

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