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 microg, 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.
authors.affiliation: The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136-2104, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Grumbles
authors.forename: Gizelda T B
authors.initials: GT
authors.lastname: Casella
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Rudinsky
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Wood
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sesodia
authors.forename: Melissa
authors.initials: M
authors.lastname: Bent
authors.forename: Christine K
authors.initials: CK
authors.lastname: Thomas
mesh_terms: D000818:Animals; D001284:Atrophy; D001369:Axons / Q000502:physiology; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D017690:Cell Transplantation; D005260:Female; D051522:Fibroblast Growth Factor 6 / Q000494:pharmacology*; D007150:Immunohistochemistry; D009046:Motor Neurons / Q000502:physiology; D018763:Muscle Fatigue / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects*; D018657:Muscle Fibers, Slow-Twitch / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology* / Q000294:innervation*; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology; D009474:Neurons / Q000637:transplantation*; D010525:Peripheral Nerves / Q000196:embryology* / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: C486116:Fgf6 protein, rat; D051522:Fibroblast Growth Factor 6; D011518:Proto-Oncogene Proteins