Muscle ciliary neurotrophic factor receptor α promotes axonal regeneration and functional recovery following peripheral nerve lesion

Nancy Lee, Rachel P. Spearry, Kendra M. Leahy, Rachel A Robitz, Dennis S. Trinh, Carter O. Mason, Rebekah J. Zurbrugg, Myra K. Batt, Richard J. Paul, A. John Maclennan

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Ciliary neurotrophic factor (CNTF) administration maintains, protects, and promotes the regeneration of both motor neurons (MNs) and skeletal muscle in a wide variety of models. Expression of CNTF receptor α (CNTFRα), an essential CNTF receptor component, is greatly increased in skeletal muscle following neuromuscular insult. Together the data suggest that muscle CNTFRα may contribute to neuromuscular maintenance, protection, and/or regeneration in vivo. To directly address the role of muscle CNTFRα, we selectively-depleted it in vivo by using a "floxed" CNTFRα mouse line and a gene construct (mlc1f-Cre) that drives the expression of Cre specifically in skeletal muscle. The resulting mice were challenged with sciatic nerve crush. Counting of nerve axons and retrograde tracing of MNs indicated that muscle CNTFRα contributes to MN axonal regeneration across the lesion site. Walking track analysis indicated that muscle CNTFRα is also required for normal recovery of motor function. However, the same muscle CNTFRα depletion unexpectedly had no detected effect on the maintenance or regeneration of the muscle itself, even though exogenous CNTF has been shown to affect these functions. Similarly, MN survival and lesion-induced terminal sprouting were unaffected. Therefore, muscle CNTFRα is an interesting new example of a muscle growth factor receptor that, in vivo under physiological conditions, contributes much more to neuronal regeneration than to the maintenance or regeneration of the muscle itself. This novel form of muscle-neuron interaction also has implications in the therapeutic targeting of the neuromuscular system in MN disorders and following nerve injury. J. Comp. Neurol. 521: 2947-2965, 2013.

Original languageEnglish (US)
Pages (from-to)2947-2965
Number of pages19
JournalJournal of Comparative Neurology
Volume521
Issue number13
DOIs
StatePublished - Sep 1 2013
Externally publishedYes

Fingerprint

Ciliary Neurotrophic Factor Receptor
Peripheral Nerves
Regeneration
Muscles
Motor Neurons
Ciliary Neurotrophic Factor
Skeletal Muscle
Maintenance
Nerve Crush
Growth Factor Receptors
Recovery of Function
Sciatic Nerve
Walking
Axons

Keywords

  • Cre recombinase
  • Mlc1f-Cre
  • Mouse
  • Muscle CNTF receptor α
  • Sciatic

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Muscle ciliary neurotrophic factor receptor α promotes axonal regeneration and functional recovery following peripheral nerve lesion. / Lee, Nancy; Spearry, Rachel P.; Leahy, Kendra M.; Robitz, Rachel A; Trinh, Dennis S.; Mason, Carter O.; Zurbrugg, Rebekah J.; Batt, Myra K.; Paul, Richard J.; Maclennan, A. John.

In: Journal of Comparative Neurology, Vol. 521, No. 13, 01.09.2013, p. 2947-2965.

Research output: Contribution to journalArticle

Lee, N, Spearry, RP, Leahy, KM, Robitz, RA, Trinh, DS, Mason, CO, Zurbrugg, RJ, Batt, MK, Paul, RJ & Maclennan, AJ 2013, 'Muscle ciliary neurotrophic factor receptor α promotes axonal regeneration and functional recovery following peripheral nerve lesion', Journal of Comparative Neurology, vol. 521, no. 13, pp. 2947-2965. https://doi.org/10.1002/cne.23324
Lee, Nancy ; Spearry, Rachel P. ; Leahy, Kendra M. ; Robitz, Rachel A ; Trinh, Dennis S. ; Mason, Carter O. ; Zurbrugg, Rebekah J. ; Batt, Myra K. ; Paul, Richard J. ; Maclennan, A. John. / Muscle ciliary neurotrophic factor receptor α promotes axonal regeneration and functional recovery following peripheral nerve lesion. In: Journal of Comparative Neurology. 2013 ; Vol. 521, No. 13. pp. 2947-2965.
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AU - Trinh, Dennis S.

AU - Mason, Carter O.

AU - Zurbrugg, Rebekah J.

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