Mouse Strain Dependent Differences in Muscle Fiber Type, Fiber Area, and Blood Perfusion in Response to Denervation Atrophy

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Date

1/13/16

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Hakimi, Javid

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East Carolina University

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Skeletal muscle atrophy caused by denervation is a serious consequence of neuropathic disease, especially diabetes. However, the only proven treatment for muscle atrophy is exercise, which can be difficult or impossible for patients with a neuropathic disease. Fortunately, as a clue to novel treatment targets, there is evidence for a genetic component that predisposes mice to have a resistance to skeletal muscle atrophy during ischemia. The aim of this study is to identify whether this strain-dependent resistance is evident in a purely denervation model of skeletal muscle atrophy. Twenty male C57BL/6 mice and twenty male BALB/C mice had their sciatic nerve sectioned in their left leg and were sham-operated in their right leg. Blood perfusion of the lower hindlimbs was measured over the next 14 days with Laser Doppler Perfusion Imager (Periscan PIM II). At 14 days post-surgery, tibialis anterior, soleus, extensor digitorum longus (EDL), gastrocnemius, and plantaris muscles were harvested and weighed. The tibialis anterior (TA) and soleus were frozen for cryosectioning and immunostained to examine fiber size. Total protein content of the TA and soleus were measured using a BCA protein assay (Pierce). Myosin heavy chain (MHC) content was measured by silver-staining homogenates of the TA and soleus. The denervated hindlimbs of the C57BL/6 mice had significantly greater perfusion than the BALB/C at day 1 (+30%), day 3 (+27%), and day 13 (+40%), while day 5 was not different. There were no differences between mouse strains in weights of the innervated muscles (p < 0.05). In response to denervation, muscles atrophied in all hindlimb muscles ranging from approximately 29% (in the EDL) to approximately 46% (in the gastrocnemius) depending on muscle. Average fiber size of the TA and soleus decreased after denervation, but no difference was found between strains. Consistent with loss of mass and fiber size, tibialis anterior muscles also lost protein content after denervation, which did not significantly differ between strains. MHC isoforms in both strains shifted from a less glycolytic nature (Type IIB) to more oxidative (Type IIA+IIX) in the TA, but remained almost unchanged in the soleus. No strain-specific differences were found. In summary, despite our previous reports of a strain-dependent difference in ischemia-related atrophy and despite the differences in tissue perfusion during denervation, muscle of the BALB/c and C57BL/6 mice atrophy to the same extend during denervation atrophy However, a strain-dependent response to blood perfusion was found, as C57BL/6 mice had greater perfusion. Funding: Interdisciplinary Research Collaboration Award, ECU

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