Muscle atrophy produced by spinal cord injury (SCI) in rats decreases muscle protein synthesis without altering mTOR kinase activity

Abstract

SCI produces muscle atrophy and derangements in nutrient homeostasis; however, the mechanisms and temporal patterning of these co‐morbidities are poorly defined. Chronic (≥10 week) SCI has been shown to down‐regulate mTOR/S6K1 signaling in soleus muscle and induce changes in body composition and lipid compartmentalization. We assessed muscle protein synthesis (MPS) and degradation in adult rats using an acute contusion injury model at spinal T3. At 7‐days post‐SCI, lean body and gastrocnemius mass were reduced (15% and 20%, respectively), compared to time‐matched controls. In vivo analysis determined this response was mediated, in part, by a 15% decrease in MPS. Contrary to expectations, phosphorylation of AKT (upstream regulator of mTOR) as well as S6K1 and 4E‐BP1 (downstream mediators of mTOR) was not reduced in muscle after SCI, compared to time‐matched sham controls. SCI tended to increase the muscle‐specific E3 ligases atrogin‐1 and MuRF1, but these changes were not statistically significant. REDD1 was also not increased following SCI. Our data suggest acute SCI in rats produces muscle atrophy primarily by reducing MPS may be mTOR‐independent. (Supported by GM38032 and NS49177)