Electron microscopic study of long‐term denervated rat skeletal muscle

Abstract

Background: This study describes the ultrastructure of long-term denervated rat extensor digitorum longus and tibialis anterior muscles, with particular emphasis on understanding the cellular basis for the reduced restorative capacity of long-term denervated muscle. Methods: In 30 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 prepared for electron microscopy. Results: Atrophy of muscle fibers was prominent by the second month post-denervation. At this time, type II fibers showed greater atrophy than type I fibers. At further periods of denervation, atrophy of all fibers was seen; and with increasing times of denervation the muscle fibers became surrounded by dense mats of collagen fibers. Muscle spindles persisted for the duration of this study. At two and four months, satellite cells showed signs of activation, such as elongated cytoplasmic processes and an increased concentration of cytoplasmic organelles. As denervation progressed , activated satellite 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 muscle fibers, and others acted as bridges between two muscle fibers. Evidence 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 morphology of individual muscle fibers varied. Some contained well-ordered lattice 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 disorganized; lipid droplets, glycogen deposits, and autopha-gic vesicles were all present in the cytoplasm of atrophic muscle fibers. Conclusions: In addition to muscle fiber atrophy, long-term denervated muscles show evidence of myofiber and capillary death, as well as the deposition of massive amounts of interstitial collagen. These changes, all of which would appear to reduce the restorative capacity of the dener-vated muscle, take place concurrently with the morphological activation of satellite cells. The latter indicates that even in the denervated condition , restorative processes occur concurrently with regressive processes.

Testosterone mediates satellite cell activation in denervated rat levator ani muscle

“…The elucidation of the influences that impinge on them and their responses is crucial to our overall understanding of the biology of regeneration and repair in skeletal muscle. The role of denervation as a mitogenic stimulus is well-documented (Aloisi et al, 1973;Schultz, 1978;Snow, 1983;McGeachie, 1989;Lu et al, 1997;Nnodim, 1999). The present study has shown that testosterone is instrumental to the evocation of the proliferative response in rat LA.…”

Activation of the vasoactive intestinal peptide 2 receptor modulates normal and atrophying skeletal muscle mass and force

“…To evaluate the functionality of the VIP receptors expressed in skeletal muscle and to validate the observation that only VPAC2R is expressed in skeletal muscle, skeletal muscles in organ bath were stimulated with either the VPACR-nonselective agonist VIP, the VPAC1R-selective agonist [K 15 ,R (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), or the VPAC2R-selective agonist Ro-25-1553, and cAMP generation was evaluated. As can be seen in Fig.…”

“…Skeletal muscle atrophy can be initiated by a variety of stimuli including, for example, disuse, nerve damage, and glucocorticoid use (2,15,17,19,31,37,40). Atrophy induces multiple changes in skeletal muscle that are independent of the atrophy-inducing stimuli, including decreased protein synthesis, increased protein degradation, alterations in contractile and metabolic enzyme protein isozymes, loss of vasculature, and remodeling of the extracellular matrix (2,5,6,22,24,25,27). Atrophy and hypertrophy are conserved processes across mammalian species.…”

Proteomic profiling of pathological and aged skeletal muscle fibres by peptide mass fingerprinting (Review)

“…The fact that muscle gene expression, protein levels and isoform patterns are closely related to innervation is illustrated by two important experimental findings. Firstly, the physical disconnection between a fibre unit and its respective motor neuron triggers rapid fibre atrophy (21) and secondly, artificial electro-stimulation causes pronounced changes in muscle activity (22). For example, the long-term dennervation of the mature rat extensor digitorum longus muscle triggers a 95% decrease in isometric contractile force and a two-third loss in muscle tissue mass within a month (23).…”