Muscle-Derived Neurotrophin-4 as an Activity-Dependent Trophic Signal for Adult Motor Neurons

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 α-bungarotoxin and increased during postnatal development and after electrical stimulation in a...

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Veröffentlicht in:	Science (American Association for the Advancement of Science) 1995-06, Vol.268 (5216), p.1495-1499
Hauptverfasser:	Funakoshi, Hiroshi, Belluardo, Natale, Arenas, Ernest, Yamamoto, Yuji, Casabona, Antonino, Persson, Håkan, Ibáñez, Carlos F.
Format:	Artikel
Sprache:	eng
Schlagworte:	Adults Animals Biochemistry Biological and medical sciences Bungarotoxins - pharmacology Cell Line Development. Senescence. Regeneration. Transplantation Electric Stimulation Electrical stimulation Exercise Fundamental and applied biological sciences. Psychology Gene Expression Regulation Individualized Instruction Medicin och hälsovetenskap Messenger RNA Motor neurons 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 Muscles Muscular system Nerve Growth Factors - biosynthesis Nerve Growth Factors - genetics Nerve Growth Factors - pharmacology Nerve Growth Factors - physiology Nerves Neuromuscular Junction - physiology Neuromuscular transmission Neurons Neurotrophic functions Neurotrophins Neurotropin Rats Rats, Inbred F344 Receptor Protein-Tyrosine Kinases - metabolism Receptor, Nerve Growth Factor Receptor, trkB Receptors, Nerve Growth Factor - metabolism Receptors, Neuropeptide - metabolism RNA RNA, Messenger - analysis RNA, Messenger - biosynthesis RNA, Messenger - genetics Rodents Sciatic Nerve - physiology Skeletal muscle Space life sciences Sprouting Synaptic Transmission Tissue grafting Vertebrates: nervous system and sense organs
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Zusammenfassung:	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 α-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.
ISSN:	0036-8075 1095-9203
DOI:	10.1126/science.7770776