Mechanisms of rodent slow-twitch skeletal muscle atrophy in response to complete inactivation by spinal-isolation

摘要

When skeletal muscles decrease their normal weight bearing activity or become chronically unloaded, as occurs during exposure to spaceflight or during prolonged bed rest (or animal equivalents such as the model of hind limb unloading), they markedly atrophy, e.g., decrease in size and lose protein due to decreases in protein balance. That is, the capacity for protein synthesis relative to the capacity for protein degradation decreases and the muscles enter a catabolic state until a new steady state of reduced muscle mass is reached. In order to gain a better understanding of how muscle inactivity/weight bearing reduction contributes to the atrophy response, we took advantage of a unique model, termed spinal isolation (SI), in which the muscle is induced into complete inactivity while maintaining an intact motor neuron connection to the target muscles. Briefly, SI involves severing the spinal cord in the distal cervical /high thoracic region, as well as in the low lumber/high sacral region. Then a complete bilateral dorsal rhizotomy is performed in between the severed regions in order to eliminate supraspinal as well as any sensory input into the spinal cord that could activate the motor neuron pool to excite the muscle. Thus, the muscles become silent and totally inactive, which leads to rapid atrophy and protein loss.