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

TLDR

NT‑4 may partly mediate the beneficial effects of exercise and electrical stimulation on neuromuscular performance. The study demonstrates that muscle‑derived NT‑4 production is activity‑dependent, rises during postnatal development and with electrical stimulation, is localized to slow type I fibers, and that intramuscular NT‑4 induces sprouting of adult motor nerves, indicating it functions as an activity‑dependent neurotrophic signal for motor neuron growth and remodeling.

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 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.