Activity-induced fiber regeneration in rat soleus muscle

In an attempt to understand why muscle recovery is limited following atroph y due to limb immobilization, satellite cell activity and muscle Liber rege neration were analyzed in rat soleus muscles. Adult rat hindlimbs were immo bilized in plaster casts for a period of two to ten weeks. Soleus muscles w ere examined by electron microscopy for evidence of fiber degeneration or r egeneration, and to quantify satellite cel; nuclei. Immunocytochemical loca lization of embryonic myosin was used to identify regenerating myofibers. S oleus muscle wet weight to body weight ratios for the casted muscles signif icantly decreased over the 10-week immobilization period. The casted muscle s displayed ultrastructural evidence of minor fiber damage, including myofi brillar atrophy, Z-disc disruption, and abnormal triadic junctions. No ultr astructural evidence of regeneration was seen in the casted animals. The nu mber of satellite cells in the casted muscles significantly decreased from 6.4% to 3.3% by eight to 10 weeks of immobilization. Approximately 1.0% of extrafusal fibers in the control soleus muscles appeared to be regenerating since they expressed embryonic myosin and were of a small diameter, while in casted muscles, only 0.1% of the fibers were embryonic myosin-positive. Following release from immobilization, a reappearance of embryonic myosin-p osit;ive fibers was noted within four days of renewed activity. In contrast to control muscles, embryonic myosin-positive fibers in the recovery muscl es included both small and large diameter fibers. Subtle changes in functio nal activity influence muscle damage and subsequent myofiber regeneration. Reduced activity reduces muscle fiber regeneration, while increased activit y, as seen by increased hindlimb weight bearing and return to normal activi ty following immobilization, increase regenerating fibers and also the expr ession of embryonic myosin in adult; fibers. Anat Rec 258:176-185, 2000. (C ) 2000 Wiley-Liss, Inc.