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Hellyer, N.1; Erickson, A.2; Zhan, W.2; Sieck, G. C.2
1Physical Medicine and Rehabilitation (Program in Physical Therapy), Mayo Clinic College of Medicine, Rochester, MN; 2Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN.
PURPOSE/HYPOTHESIS: Muscle cross sectional area is an important determinant of muscle performance. There are several external factors that regulate muscle cross sectional area such as muscle loading, contraction history, and neuronal activity. Each of these factors ultimately regulates cellular programs within muscle to induce changes in muscle size. The purpose of this study was to examine one potential regulator of muscle cross sectional area, the cellular protein kinase Akt, and its activity level following denervation‐induced muscle atrophy. NUMBER OF SUBJECTS: Eight Sprague‐Dawley rats. MATERIALS/METHODS: Diaphragm muscles from Sprague‐Dawley rats were analyzed at days 3, 7, and 14 following phrenic nerve denervation. Muscle protein was extracted and western analysis was performed. Akt activity level was measured by the ratio of phosphorylated Akt to total Akt. RESULTS: We observed a slight increase in Akt activity following 3 days of denervation. Akt activity levels at days 7 and 14 declined to similar levels as observed for untreated animals. Interestingly, our lab has previously observed a slight increase in cross sectional area of diaphragm fibers 3 days after denervation that is followed by atrophy at days 7 and 14. CONCLUSIONS: We conclude that the activity level of Akt may be a marker of changes in muscle growth following denervation. We further speculate that the Akt activity levels may be regulated by a trophic factor released from the phrenic motor neuron. CLINICAL RELEVANCE: Our work in understanding molecular regulators of muscle growth may lead to the development of therapeutic interventions to limit muscle atrophy following nerve injury. This study supported by NIH grant HL37680.
© 2004 Neurology Section, APTA
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