MUSCLE-DERIVED NEUROTROPHIN-4 AS AN ACTIVITY-DEPENDENT TROPHIC SIGNALFOR ADULT MOTOR-NEURONS

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