Satellite cell activation after muscle damage in young and adult rats

Abstract

Background: Level exercise leads to focal structural damage in muscle fibers and to an increase of creatine kinase in the blood. We questioned whether it also induces activation of young and adult muscle satellite cells toward proliferation. Methods: Rats of two different ages, 6 and 16 weeks, were forced to run on a level treadmill and killed at different time intervals. The temporal profile, up to 3 weeks, of muscle damage was investigated by quantification of the focally disturbed fiber area in longitudinal sections of the m. soleus. Bromodeoxyuridine (BrdU) was injected before death to determine the labeling index of satellite cells. Labeled and unlabeled satellite cells, myonuclei, and fibers were counted in cross sections of the belly part of the muscles. Results: The muscle fiber damage differed in both amount and temporal profile between young and older animals. Damage was already visible immediately after running. However, whereas in the younger animal the amount of damage increased gradually in time until 8% at 48 hours and disappeared to almost control levels at 1 week after running, in the older animals the amount of damage was lower but remained present for at least 2 weeks. The cell kinetic data on both groups showed a proliferation response of satellite cells throughout the muscle. The effects were most pronounced in the older rats. In these rats a large increase of the labeling index was found between 24 hours and 1 week, whereas the total number of satellite cells was consistently higher from 2 days on until 2 weeks after running. In the younger animals roughly the same time pattern was observed. Conclusion: Since the damage differed in amount and time between the two age groups, we conclude that the quick and huge proliferation response is due to leakage of mitogenic factors through small membrane disruptions that are generated during the exercise itself.