ELECTRON-MICROSCOPIC STUDY OF LONG-TERM DENERVATED RAT SKELETAL-MUSCLE

Background: This study describes the ultrastructure of long-term dener vated rat extensor digitorum longus and tibialis anterior muscles, wit h particular emphasis on understanding the cellular basis for the redu ced restorative capacity of long-term denervated muscle. Methods: In 3 0 male WI/HicksCar rats, the right hindleg was denervated for periods of 1, 2, 4, 5.5, 6, 7, 12, 14, and 18 months before tissues were prepa red for electron microscopy. Results: Atrophy of muscle fibers was pro minent by the second month post-denervation. At this time, type II fib ers showed greater atrophy than type I fibers. At further periods of d enervation, atrophy of all fibers was seen; and with increasing times of denervation the muscle fibers became surrounded by dense mats of co llagen fibers. Muscle spindles persisted for the duration of this stud y. At two and four months, satellite cells showed signs of activation, such as elongated cytoplasmic processes and an increased concentratio n of cytoplasmic organelles. As denervation progressed, activated sate llite cells became more widely separated from their associated muscle fibers, and basal lamina material was deposited between the satellite cells and muscle fibers. Some satellite cells broke free from their mu scle fibers, and others acted as bridges between two muscle fibers. Ev idence was seen of both muscle fiber degeneration and the regeneration of new muscle fibers, often more than one regenerating fiber beneath a single basal lamina. Loose folds of basal lamina were often present around atrophic muscle fibers. As denervation progressed, the morpholo gy of individual muscle fibers varied. Some contained well-ordered lat tice arrays of myofilaments, whereas in others considerable sarcomeric disorganization was evident. Mitochondria became smaller and rounded; elements of the sarcoplasmic reticulum proliferated and became more d isorganized; lipid droplets, glycogen deposits, and autophagic vesicle s were all present in the cytoplasm of atrophic muscle fibers. Conclus ions: In addition to muscle fiber atrophy, long-term denervated muscle s show evidence of myofiber and capillary death, as well as the deposi tion of massive amounts of interstitial collagen. These changes, all o f which would appear to reduce the restorative capacity of the denerva ted muscle, take place concurrently with the morphological activation of satellite cells. The latter indicates that even in the denervated c ondition, restorative processes occur concurrently with regressive pro cesses. (C) 1997 Wiley-Liss, Inc.