Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons

Science. 1995 Jun 9;268(5216):1495-9. doi: 10.1126/science.7770776.

Abstract

The production of neurotrophin-4 (NT-4) in rat skeletal muscle was found to depend on muscle activity. The amounts of NT-4 messenger RNA present decreased after blockade of neuromuscular transmission with alpha-bungarotoxin and increased during postnatal development and after electrical stimulation in a dose-dependent manner. NT-4 immunoreactivity was detected in slow, type I muscle fibers. Intramuscular administration of NT-4 induced sprouting of intact adult motor nerves. Thus, muscle-derived NT-4 acted as an activity-dependent neurotrophic signal for growth and remodeling of adult motor neuron innervation. NT-4 may thus be partly responsible for the effects of exercise and electrical stimulation on neuromuscular performance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bungarotoxins / pharmacology
  • Cell Line
  • Electric Stimulation
  • Gene Expression Regulation
  • Motor Neurons / physiology*
  • Muscle Denervation
  • Muscle Development
  • Muscle Fibers, Slow-Twitch / chemistry
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / growth & development
  • Muscle, Skeletal / innervation
  • Muscle, Skeletal / physiology*
  • Nerve Growth Factors / biosynthesis
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / pharmacology
  • Nerve Growth Factors / physiology*
  • Neuromuscular Junction / physiology
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Inbred F344
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, Nerve Growth Factor
  • Receptor, trkB
  • Receptors, Nerve Growth Factor / metabolism
  • Receptors, Neuropeptide / metabolism
  • Sciatic Nerve / physiology
  • Synaptic Transmission

Substances

  • Bungarotoxins
  • Nerve Growth Factors
  • RNA, Messenger
  • Receptor, Nerve Growth Factor
  • Receptors, Nerve Growth Factor
  • Receptors, Neuropeptide
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkB
  • neurotrophin 4