The Effect of Treadmill Exercise on Denervation Induced Muscle Atrophy In Aged Rat

Abstract

Introduction: Partial denervation in old people are common, for example peripheral polyneuropathy, motor neuron disease and lumbar or cervical radiculopathy including spinal stenosis. It is important to develop interventions to reduce or restore the muscle degradation in atrophy induced by denervation in addition to sarcopenia. Exercise has been reported to reduce denervation induced atrophy of skeletal muscle in young rats. However, the effect of exercise on denervated muscle atrophy in aged rat has not been well known. The purpose of this study is to investigate the effect of treadmill exercise on denervation induced muscle atrophy in aged rat.

Methods: Aged male Sprague-Dawley rats (22 months) were randomly assigned to three groups (normal control (NC, n=7), denervation exercise (DE, n=8), denervation control (DC, n=8)). Partial denervation was performed by temporary compression of right sciatic nerve. From two weeks after denervation, treadmill resistance exercises with alternative concentric and eccentric mode were given to DE group for two weeks. Four weeks after the injury, muscle wet weight (MWW) ratio, myosin heavy chain (MHC) isoform composition from muscle homogenate and single muscle fibers and the expression of atrogene (Muscle RING Finger-1

MuRF1) and calpain-3 were measured in gastrocnemius and soleus muscles. Fiber cross sectional areas (FCSAs) were measured in gastrocnemius muscles.

Results: In denervation groups (DC and DC), MWW ratio of gastrocnemius and soleus and FCSA of gastrocnemius were significantly smaller than in NC and those were not significantly different between DC and DE. In gastrocnemius, the proportions of MHC types I and IIx isoforms in denervation (DC and DE) were significantly different compared with NC and no differences were found between DC and DE. The proportion of hybrid fiber (IIx/IIb) of single muscle fiber in gastrocnemius was greater in DE and the proportion of another hybrid fiber (IIx/I) was greater in DC. In soleus, there were no differences of the proportions of MHC isoforms among all groups. Calpain-3 expression of gastrocnemius had a tendency to increase in DC and decrease in DE but there was no significant difference. Calpain-3 expression of soleus was not significantly different among all groups. MuRF-1 expression of gastrocnemius was significantly higher in DC than NC and showed decreased tendency with no significant difference in DE. MuRF-1 expression of soleus was higher in DC than NC and lower in DE than DC, which suggests denervation induced up-regulation of MuRF-1 and exercise after partial denervation suppressed MuRF-1 activation in gastrocnemius and soleus.

Conclusions: In aged rats with atrophied skeletal muscle caused by partial denervation, treadmill resistance exercise induced down-regulation of MuRF-1 with small features of muscle plasticity but failed to make significant morphologic changes. We suppose that treadmill exercise after partial denervation in aged rats can attenuate the degradation of muscle protein on the molecular level under the surface at 4 weeks. Further studies with longer training duration are necessary to identify gross changes following treadmill exercise in denervated old rats.