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

Abstract

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 x 3 h with 30 min rest periods in between, 14 m min-1, slope 6 degrees) 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 fibers 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 less than 0.01 signed-rank test), and more so after repeated running (12.0 +/- 2.5%, n = 1505, 6 muscles, P less than 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 less than 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.