Long-term delivery of FGF-6 changes the fiber type and fatigability of muscle reinnervated from embryonic neurons transplanted into adult rat peripheral nerve

Robert M. Grumbles, Gizelda T B Casella, Michelle J. Rudinsky, Patrick Wood, Sanjay Sesodia, Melissa Bent, Christine K Thomas

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Motoneuron death leads to muscle denervation and atrophy. Transplantation of embryonic neurons into peripheral nerves results in reinnervation and provides a strategy to rescue muscles from atrophy independent of neuron replacement in a damaged or diseased spinal cord. But the count of regenerating axons always exceeds the number of motor units in this model, so target-derived trophic factor levels may limit reinnervation. Our aim was to examine whether long-term infusion of fibroblast growth factor-6 (FGF-6) into denervated medial gastrocnemius muscles improved the function of muscles reinnervated from neurons transplanted into nerve of adult Fischer rats. Factor delivery (10 μg, 4 weeks) began after sciatic nerve transection. After a week of nerve degeneration, 1 million embryonic day 14-15 ventral spinal cord cells were transplanted into the distal tibial stump as a neuron source. Ten weeks later, neurons that expressed motoneuron markers survived in the nerves. More myelinated axons were in nerves to saline-treated muscles than in FGF-6-treated muscles. However, each group showed comparable reductions in muscle fiber atrophy because of reinnervation. Mean reinnervated fiber area was 43%-51% of non-denervated fibers. Denervated fiber area averaged 11%. FGF-6-treated muscles were more fatigable than other reinnervated muscles but had stronger motor units and fewer type I fibers than did saline-treated muscles. FGF-6 thus influenced function by changing the type of fiber reinnervated by transplanted neurons. Deficits in FGF-6 may also contribute to the increase in type I fibers in muscles reinnervated from peripheral axons, suggesting that the effects of FGF-6 on fiber type are independent of the neuron source used for reinnervation.

Original languageEnglish
Pages (from-to)1933-1942
Number of pages10
JournalJournal of Neuroscience Research
Volume85
Issue number9
DOIs
StatePublished - Jul 1 2007

Fingerprint

Fibroblast Growth Factor 6
Peripheral Nerves
Neurons
Muscles
Muscular Atrophy
Axons
Motor Neurons
Muscle Denervation
Slow-Twitch Muscle Fibers
Nerve Degeneration
Spinal Cord Diseases
Inbred F344 Rats
Sciatic Nerve
Spinal Cord
Skeletal Muscle
Transplantation

Keywords

  • Axon regeneration
  • Denervated skeletal muscle
  • Motoneuron transplantation
  • Motor unit force

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Long-term delivery of FGF-6 changes the fiber type and fatigability of muscle reinnervated from embryonic neurons transplanted into adult rat peripheral nerve. / Grumbles, Robert M.; Casella, Gizelda T B; Rudinsky, Michelle J.; Wood, Patrick; Sesodia, Sanjay; Bent, Melissa; Thomas, Christine K.

In: Journal of Neuroscience Research, Vol. 85, No. 9, 01.07.2007, p. 1933-1942.

Research output: Contribution to journalArticle

Grumbles, Robert M. ; Casella, Gizelda T B ; Rudinsky, Michelle J. ; Wood, Patrick ; Sesodia, Sanjay ; Bent, Melissa ; Thomas, Christine K. / Long-term delivery of FGF-6 changes the fiber type and fatigability of muscle reinnervated from embryonic neurons transplanted into adult rat peripheral nerve. In: Journal of Neuroscience Research. 2007 ; Vol. 85, No. 9. pp. 1933-1942.
@article{0eaa39712bc34a62a9f773335dda86ec,
title = "Long-term delivery of FGF-6 changes the fiber type and fatigability of muscle reinnervated from embryonic neurons transplanted into adult rat peripheral nerve",
abstract = "Motoneuron death leads to muscle denervation and atrophy. Transplantation of embryonic neurons into peripheral nerves results in reinnervation and provides a strategy to rescue muscles from atrophy independent of neuron replacement in a damaged or diseased spinal cord. But the count of regenerating axons always exceeds the number of motor units in this model, so target-derived trophic factor levels may limit reinnervation. Our aim was to examine whether long-term infusion of fibroblast growth factor-6 (FGF-6) into denervated medial gastrocnemius muscles improved the function of muscles reinnervated from neurons transplanted into nerve of adult Fischer rats. Factor delivery (10 μg, 4 weeks) began after sciatic nerve transection. After a week of nerve degeneration, 1 million embryonic day 14-15 ventral spinal cord cells were transplanted into the distal tibial stump as a neuron source. Ten weeks later, neurons that expressed motoneuron markers survived in the nerves. More myelinated axons were in nerves to saline-treated muscles than in FGF-6-treated muscles. However, each group showed comparable reductions in muscle fiber atrophy because of reinnervation. Mean reinnervated fiber area was 43{\%}-51{\%} of non-denervated fibers. Denervated fiber area averaged 11{\%}. FGF-6-treated muscles were more fatigable than other reinnervated muscles but had stronger motor units and fewer type I fibers than did saline-treated muscles. FGF-6 thus influenced function by changing the type of fiber reinnervated by transplanted neurons. Deficits in FGF-6 may also contribute to the increase in type I fibers in muscles reinnervated from peripheral axons, suggesting that the effects of FGF-6 on fiber type are independent of the neuron source used for reinnervation.",
keywords = "Axon regeneration, Denervated skeletal muscle, Motoneuron transplantation, Motor unit force",
author = "Grumbles, {Robert M.} and Casella, {Gizelda T B} and Rudinsky, {Michelle J.} and Patrick Wood and Sanjay Sesodia and Melissa Bent and Thomas, {Christine K}",
year = "2007",
month = "7",
day = "1",
doi = "10.1002/jnr.21323",
language = "English",
volume = "85",
pages = "1933--1942",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "9",

}

TY - JOUR

T1 - Long-term delivery of FGF-6 changes the fiber type and fatigability of muscle reinnervated from embryonic neurons transplanted into adult rat peripheral nerve

AU - Grumbles, Robert M.

AU - Casella, Gizelda T B

AU - Rudinsky, Michelle J.

AU - Wood, Patrick

AU - Sesodia, Sanjay

AU - Bent, Melissa

AU - Thomas, Christine K

PY - 2007/7/1

Y1 - 2007/7/1

N2 - Motoneuron death leads to muscle denervation and atrophy. Transplantation of embryonic neurons into peripheral nerves results in reinnervation and provides a strategy to rescue muscles from atrophy independent of neuron replacement in a damaged or diseased spinal cord. But the count of regenerating axons always exceeds the number of motor units in this model, so target-derived trophic factor levels may limit reinnervation. Our aim was to examine whether long-term infusion of fibroblast growth factor-6 (FGF-6) into denervated medial gastrocnemius muscles improved the function of muscles reinnervated from neurons transplanted into nerve of adult Fischer rats. Factor delivery (10 μg, 4 weeks) began after sciatic nerve transection. After a week of nerve degeneration, 1 million embryonic day 14-15 ventral spinal cord cells were transplanted into the distal tibial stump as a neuron source. Ten weeks later, neurons that expressed motoneuron markers survived in the nerves. More myelinated axons were in nerves to saline-treated muscles than in FGF-6-treated muscles. However, each group showed comparable reductions in muscle fiber atrophy because of reinnervation. Mean reinnervated fiber area was 43%-51% of non-denervated fibers. Denervated fiber area averaged 11%. FGF-6-treated muscles were more fatigable than other reinnervated muscles but had stronger motor units and fewer type I fibers than did saline-treated muscles. FGF-6 thus influenced function by changing the type of fiber reinnervated by transplanted neurons. Deficits in FGF-6 may also contribute to the increase in type I fibers in muscles reinnervated from peripheral axons, suggesting that the effects of FGF-6 on fiber type are independent of the neuron source used for reinnervation.

AB - Motoneuron death leads to muscle denervation and atrophy. Transplantation of embryonic neurons into peripheral nerves results in reinnervation and provides a strategy to rescue muscles from atrophy independent of neuron replacement in a damaged or diseased spinal cord. But the count of regenerating axons always exceeds the number of motor units in this model, so target-derived trophic factor levels may limit reinnervation. Our aim was to examine whether long-term infusion of fibroblast growth factor-6 (FGF-6) into denervated medial gastrocnemius muscles improved the function of muscles reinnervated from neurons transplanted into nerve of adult Fischer rats. Factor delivery (10 μg, 4 weeks) began after sciatic nerve transection. After a week of nerve degeneration, 1 million embryonic day 14-15 ventral spinal cord cells were transplanted into the distal tibial stump as a neuron source. Ten weeks later, neurons that expressed motoneuron markers survived in the nerves. More myelinated axons were in nerves to saline-treated muscles than in FGF-6-treated muscles. However, each group showed comparable reductions in muscle fiber atrophy because of reinnervation. Mean reinnervated fiber area was 43%-51% of non-denervated fibers. Denervated fiber area averaged 11%. FGF-6-treated muscles were more fatigable than other reinnervated muscles but had stronger motor units and fewer type I fibers than did saline-treated muscles. FGF-6 thus influenced function by changing the type of fiber reinnervated by transplanted neurons. Deficits in FGF-6 may also contribute to the increase in type I fibers in muscles reinnervated from peripheral axons, suggesting that the effects of FGF-6 on fiber type are independent of the neuron source used for reinnervation.

KW - Axon regeneration

KW - Denervated skeletal muscle

KW - Motoneuron transplantation

KW - Motor unit force

UR - http://www.scopus.com/inward/record.url?scp=34447302334&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34447302334&partnerID=8YFLogxK

U2 - 10.1002/jnr.21323

DO - 10.1002/jnr.21323

M3 - Article

VL - 85

SP - 1933

EP - 1942

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 9

ER -