Muscle fibre loss and reinnervation after long-term denervation

Abstract

Cutaneous pectoris muscles of frog (Rana temporaria) were investigated 19.5-40 months after denervation. On whole mounts a heavy reduction in size and number of muscle fibres is noticed; in two muscles studied with semithin and ultrathin sections the number of remaining muscle fibres is 149 and around 120, while one of the contralateral muscles contains 250 and control muscles of equal sized frogs between 220 and 320 (n = 18) fibres. By electron microscopy muscle fibres undergoing degeneration or phagocytosis can be seen (3 of 20 muscle fibres present in a single ultrathin cross-section). On the other hand several profiles contained within one common basal lamina sheath are present in 14 of 20 fibres, indicating satellite cell proliferation. In one preparation 40 months after denervation not a single muscle fibre or axon is present, suggesting that eventually, without nerve supply, muscle fibres entirely disappear. Upon spontaneous reinnervation or implantation of the hypoglossal nerve 16 months after denervation, synapses are formed with the remaining muscle fibres. When studied 3.5-24 months after nerve implantation muscles innervated by few axons only (less than 10, 10-20 axons) contain a low number of muscle fibres (mean 44 +/- 41 SD, n = 6), while all muscles with a larger number of axons have more than 150 muscle fibres (n = 6). This indicates that unless large numbers of axons regenerate and/or when reinnervation is delayed muscle fibre loss continues to occur. The presence in one muscle of motor axons but only six muscle fibres 24 months after nerve implantation indicates that muscle fibre loss cannot be reversed, or recovery is extremely slow. This observation is interpreted as evidence for the exhaustibility of the satellite cell pool.

Expression pattern of M‐cadherin in normal, denervated, and regenerating mouse muscles

“…Also after muscle denervation, satellite cells proliferate (McGeachie, 1985;Murray and Robbins, 1982a) which might be important for prolonged main-0 1994 WILEY-LISS. INC. tenance of muscle tissue in the absence of nerve (Anzil and Wernig, 1989;Schmalbruch et al, 1991).…”

The Use of Anabolic Steroids as a Strategy in Reversing Denervation Atrophy after Delayed Nerve Repair

“…With prolonged denervation, however, this pool of cells ultimately becomes exhausted. Loss of this important regenerative component may explain why denervation atrophy eventually becomes irreversible [1,17,29].…”

“…Prevailing theories point to alterations in contractile protein concentrations and composition [10,20,25] as well as the degradation of the satellite cell population. Satellite cells, which are reparative mononuclear progenitor cells found in muscle tissue, normally divide, proliferate [1,40,46], and become incorporated into damaged or denervated muscle fibers [1,24,38] to preserve or rebuild mass. With prolonged denervation, however, this pool of cells ultimately becomes exhausted.…”

Effects of nandrolone on recovery after neurotization of chronically denervated muscle in a rat model

“…20,36 This ability to self-replicate is limited, however, and the eventual exhaustion of this population is linked to the development of "irreversible denervation atrophy." 1,16,27 Anabolic steroids, which are basically synthetic forms of testosterone designed to maximize anabolic effects while minimizing androgenic side effects, may have a potential role in reversing denervation atrophy. Salmons demonstrated improved size and strength in the tibialis anterior muscle of female rabbits following 12 weeks of anabolic steroid administration.…”