ACTH peptides stimulate motor nerve sprouting in development

Maturational changes at the neuromuscular junction (nmj) of rat neonates were studied using scanning electron microscopy and light microscopy that permitted quantification of muscle fiber diameter, length of nerve terminal branching, end-plate area, and perimeter. Administration of ACTH 4–10 (10 μg/kg s.c. daily from day of birth) stimulated nerve terminal branching, an effect most evident in 14-day-old pups. The trisubstituted derivative of ACTH 4–9 (Org 2766) when administered at 0.01 μg/kg/daily, had a more potent effect, increasing end-plate perimeter and nerve terminal branching at the first postnatal week and markedly increasing only nerve terminal branching at 14 days of age. This is a dose-responsive action since 10 μg/kg/daily severely inhibits nerve sprouting. By 21 days, there were no differences between peptide- and saline-treated neonates. Peptide-induced sprouting was elicited only in the first 2 weeks of postnatal life. This time course corresponds with the critical period for nmj maturation and ceases when polyneuronal innervation of muscle fibers also terminates. It is suggested that ACTH peptides may exert a physiological role on nerve sprouting during development.