Lack of motor recovery after prolonged denervation of the neuromuscular junction is not due to regenerative failure

Miyuki Sakuma, Grzegorz Gorski, Shu Hsien Sheu, Stella Lee, Lee B. Barrett, Bhagat Singh, Takao Omura, Alban Latremoliere, Clifford J. Woolf

Research output: Contribution to journalArticle

Abstract

Motor axons in peripheral nerves have the capacity to regenerate after injury. However, full functional motor recovery rarely occurs clinically, and this depends on the nature and location of the injury. Recent preclinical findings suggest that there may be a time after nerve injury where, while regrowth to the muscle successfully occurs, there is nevertheless a failure to re-establish motor function, suggesting a possible critical period for synapse reformation. We have now examined the temporal and anatomical determinants for the re-establishment of motor function after prolonged neuromuscular junction (NMJ) denervation in rats and mice. Using both sciatic transection-resuture and multiple nerve crush models in rats and mice to produce prolonged delays in reinnervation, we show that regenerating fibres reach motor endplates and anatomically fully reform the NMJ even after extended periods of denervation. However, in spite of this remarkably successful anatomical regeneration, after 1 month of denervation there is a consistent failure to re-establish functional recovery, as assessed by behavioural and electrophysiological assays. We conclude that this represents a failure in re-establishment of synaptic function, and the possible mechanisms responsible are discussed, as are their clinical implications.

Original languageEnglish (US)
Pages (from-to)451-462
Number of pages12
JournalEuropean Journal of Neuroscience
Volume43
Issue number3
DOIs
StatePublished - Feb 1 2016
Externally publishedYes

Keywords

  • Critical period
  • Motor functional recovery
  • Neuromuscular junction
  • Peripheral nerve injury
  • Regeneration

ASJC Scopus subject areas

  • Neuroscience(all)

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