Axonal sprouting and changes in fibre types after running-induced muscle damage

Summary We have recently observed increase in Type I fibres in mouse soleus — but not extensor digitorum longus — muscles as a result of repeated muscle damage induced by voluntary wheel running. The most likely mechanism underlying the changes in fibre type composition is a redistribution of motor units with axonal sprouting and formation of new synapses. To test this hypothesis we exercised mice on a motor-driven treadmill once (3 × 3 h with 30 min rest periods in between, 14 m min^–1, slope 6 °) or repeatedly (8–10 times at intervals of 3–5 days) and quantified axonal sprouting after staining with zinc iodide-osmium. In the contralateral solei, muscle damage and fibre type changes were evaluated with standard histochemical techniques.Significant numbers of damaged muscle fibres were found 0–15 days after a single exercise as compared to unexercised control animals (range 0.0–0.3% of the fibres in sedentary,n=5,vs 2.1–14.8% in exercised muscles,n=10) and repeated damage occurred in repeatedly exercised animals. In muscles of sedentary animals 3.8 ± 1.4% SD of the examined endplates (n=880, 5 muscles) had nodal or terminal sprouts. The incidence of sprouting was significantly elevated 3–21 days after a single exercise (7.5 ± 1.8%,n=2855, 12 muscles,P < 0.01 signed-rank test), and more so after repeated running (12.0 ± 2.5%,n=1505, 6 muscles,P < 0.01). Fibre type distributions were not different from controls 3 weeks after a single running episode, but after the 6–7 weeks of repeated running a significant increase in undifferentiated fibres at the cost of Type II fibres was found (9.7 ± 3.4% versus 1.0 ± 0.5% in sedentary controls,P < 0.05,t-test); undifferentiated fibres express both Type I and Type II myofibrillar ATPase and are considered as fibres in the process of changing their types. These observations strongly support the assumption that sprouting and formation of new synapses — followed by motor unit enlargement and redistribution — occur as a result of muscle damage.