REGENERATION AND INNERVATION OF NORMAL AND DYSTROPHIC MUSCLE CULTURED WITH NORMAL AND DYSTROPHIC SPINAL CORD

Abstract

Teased strips of normal or dystrophic adult mouse muscle were cultured with embryonic normal or ‘dystrophic’ mouse spinal cord explants, in order to determine whether muscular dystrophy is of primary myopathic or neuropathic origin. When cultured with normal spinal cord, both normal and dystrophic muscle regenerated to form new cross‐striated muscle fibres with peripherally located nuclei and showing spontaneous, synchronized contractions. Silver impregnation and acetyl‐cholinesterase activity showed that neuromuscular junctions were formed. In marked contrast, both normal and dystrophic muscle cultured with spinal cord from dystrophic animals failed to show such functional regeneration, and neuromuscular junctions could not be identified. Only a few myotubes were formed, and these were rarely cross‐striated, had internal nuclei, and only some showed asynchronous fibrillatory contractions. These results strongly suggest that murine muscular dystrophy has a neural pathogenesis. Histochemical reactions were carried out on serial frozen sections of the regenerated muscle fibres, and also of embryonic mouse muscle cultured in cord‐myotome explants, to determine whether ‘fibre types’ were formed. All the fibres gave uniformly strong or medium reactions to phosphorylase, NADH‐TR, myofibrillar ATPase, ATPase after acid preincubation, and the PAS reaction for glycogen, except a few fibres in an embryonic muscle which gave weak reactions for all enzymes. Histochemical fibre types were not formed. Two studies of explants of human muscle in association with normal embryonic mouse spinal cord resulted in the establishment of functional neuromuscular contact and the production of well striated myotubes, with peripherally placed nuclei and spontaneous regular contractions.