QUANTITATIVE STUDY OF THE EFFECTS OF LONG-TERM DENERVATION ON THE EXTENSOR DIGITORUM LONGUS MUSCLE OF THE RAT

Background: In order to understand the cellular basis underlying the p rogressively poorer restorative capacity of long-term denervated muscl e, we determined the effects of long-term denervation on the muscle fi bers and satellite cell population of the rat extensor digitorum longu s (EDL) muscle, Methods: In 36 male rats, the right hind legs were den ervated, and EDL muscles were removed 2, 4, 7, 12, and 18 months later , Muscles were either fixed for electron microscopic analysis or were dissociated into individual muscle fibers for direct fiber counting or for confocal microscopic analysis, Results: The percentage of satelli te cells rose from the 2.8% control value to 9.1% at 2 months of dener vation; thereafter the percentage decreased to 1.1% at 18 months of de nervation, The number of myonuclei per muscle fiber steadily declined from 410 in 4 month control muscle to 158 in 7 month denervated muscle , Up to 7 months of denervation, the total number of muscle fibers per muscle remained relatively constant at somewhat over 5,000, The calcu lated total satellite cell population in 4 month denervated EDL muscle was the same as that of controls at 65,000, but by 7 months of denerv ation it had declined to 21,000, With increasing time of denervation, the number of cross-sectional profiles of muscle fibers not containing nuclei rose from 14% in control muscle to 49% in 12 month denervated muscle, This was correlated with a pronounced regular clumping of the nuclei, with pronounced nonnucleated segments between nuclear clumps, Conclusions: Increasing times of denervation are accompanied by a pron ounced decline in the number of myonuclei per muscle fiber and an init ial rise and subsequent fall in satellite cell number, These changes a re correlated with a decreasing restorative ability of these muscles o ver the same periods of denervation, Further work on the proliferative capacity of the remaining satellite cells is necessary before firm qu antitative conclusions can be made. (C) 1997 Wiley-Liss, Inc.