Reparative myogenesis in long‐term denervated skeletal muscles of adult rats results in a reduction of the satellite cell population

Abstract

This study, conducted on 25-month denervated rat hindlimb muscles, was directed toward elucidating the basis for the poor regeneration that is observed in long-term denervated muscles. Despite a ϳ97.6% loss in mean cross-sectional area of muscle fibers, the muscles retained their fascicular arrangement, with the fascicles containing ϳ1.5 times more fibers than age-matched control muscles. At least three distinct types of muscle fibers were observed: degenerating, persisting (original), and newly formed (regenerated) fibers. A majority of newly formed fibers did not appear to undergo complete maturation, and morphologically they resembled myotubes. Sites of former motor end-plates remained identifiable in persisting muscle fibers. Nuclear death was seen in all types of muscle fibers, especially in degenerating fibers. Nevertheless, the severely atrophic skeletal muscles continued to express developmentally and functionally important proteins, such as MyoD, myogenin, adult and embryonic subunits of the nicotinic acetylcholine receptor, and neural-cell adhesion molecule. Despite the prolonged period of denervation, slow and fast types of myosin were found in surviving muscle fibers. The number of satellite cells was significantly reduced in long-term denervated muscles, as compared with age-matched control muscles. In 25-month denervated muscle, satellite cells were only attached to persisting muscle fibers, but were never seen on newly formed fibers. Our data suggest that the absence of satellite cells in a population of immature newly formed muscle fibers that has arisen as a result of continuous reparative myogenesis may be a crucial, although not necessarily the only, factor underlying the poor regenerative ability of long-term denervated muscle. Anat Rec 263: 139 -154, 2001.

Atrophy, but not necrosis, in rabbit skeletal muscle denervated for periods up to one year

“…As a result of the changes during the first phase the muscle declines to 20 -30% of its original mass by 3-4 wk (5,8,25,44,52,60), and by 1-2 mo it develops only 25% of its original isometric tetanic tension (8,47). In the denervated rat EDL muscle, tetanic force is reported to decline even further over this period, to 1-3% of control values (1,14,30); at this stage mean fiber area is only 20 -30% of control (1,46), falling to 2.5% of control over subsequent months (1,13). In the rabbit TA muscle, we observed a decrease of ϳ50% in wet weight at 10 wk after denervation, with no further decline up to 51 wk.…”

“…The mass of the affected muscles falls rapidly within 5-7 days of axotomy (11,18,22,25,55,57,58) and declines further to 30 -50% of control weight in succeeding weeks (1,5,11,14,23,41,60). After several months, muscle weight stabilizes at ϳ5-20% of control (1,13,45).…”

“…The mass of the affected muscles falls rapidly within 5-7 days of axotomy (11,18,22,25,55,57,58) and declines further to 30 -50% of control weight in succeeding weeks (1,5,11,14,23,41,60). After several months, muscle weight stabilizes at ϳ5-20% of control (1,13,45).Within the muscles, individual fibers show a reduction of ϳ70% in cross-sectional area (CSA) over a period of months (5,14,21,37), and over 90% (1,21,45) in the longer term. Initially, fast (type II) fibers are more susceptible to atrophy than slow (type I) fibers (5,7,32,38,48,54,59), but over more prolonged periods the fiber types atrophy to a similar extent (6, 54).…”

“…Although these features appear to have their counterparts in denervated muscles of the rat, there is a marked difference in timescale: changes in human muscle that take place over a period of years can be observed within a few months in the rat. Furthermore, there is little evidence in humans of the extensive necrosis and regeneration that have been reported in a number of studies of denervated muscles in the rat (13,45).…”

Denervation and Castration Effects on the Cross‐Sectional Area of Pubococcygeus Muscle Fibers in Male Rats

“…There are many factors that can modify the cross-sectional area such as immobilization, starvation, aging, gonadal hormones levels, and denervation Jackman and Kandarian, 2004). In rats, skeletal muscles are drastically affected by denervation which reduces weight and fiber size (Nnodim, 1999;Dedkov et al, 2001), commonly accompanied by muscle fiber nuclei loss as well as muscle fiber death (Borisov and Carlson, 1995). Additionally, denervation leads to an increase in packed bundles of collagen fibers, an early increase followed by a decline in satellite cell number , and a fast mass loss resulting in a lack of contractile force (Araki et al, 1991).…”