Skeletal Muscle - Atrophy

Skeletal muscle atrophy can occur due to degenerative processes originating within the skeletal muscle fibers, secondary to denervation (denervation atrophy), or spontaneously in aging rodents. It is a common reaction to any injury that results in the degradation and/or loss of myofiber organelles. Examples include disuse, cachexia, nutritional or metabolic derangements, vascular insufficiency, disturbances of hormonal growth control mechanisms, and administration of myotoxic xenobiotics. Compensatory hypertrophy of surviving/unaffected myofibers is often present concomitantly, regardless of the cause.

The main histologic feature of skeletal muscle atrophy is a reduction in myofiber diameter (Figure 1 and Figure 2). Affected myofibers are often rounded to angular with hypereosinophilic sarcoplasm. In denervation atrophy, the characteristic histologic feature is that of compressed angular myofibers with crowded nuclei. Atrophy due to nonneurogenic causes, such as that induced by the administration of myotoxic xenobiotics, often lacks these fibers and is instead accompanied by traditional myopathic changes, such as necrotic or hyalinized myofibers, split or fragmented myofibers, and myofibers with central nuclei. Spontaneous atrophy of aging rodents (often referred to as hind leg myopathy) is histologically characterized by decreased myofiber size and number; increased myofiber size variation; increased accumulation of degenerative inclusion bodies, lipofuscin, and lipid droplets; and increased connective tissue. Angulated myofibers are often present, suggesting a possible role of spinal degeneration within this process. However, spinal nerve lesions are not consistently observed in all affected animals; the pathogenesis remains unclear. This condition is predominately noted in the hind limbs of affected rats. It has been described in several strains of rats, including Wistar and Sprague-Dawley, but has not been recorded in the F344 rat.

Atrophy can uniformly affect myofibers or selectively target specific muscle fiber types. Type II fibers are selectively affected when atrophy is associated with disuse, cachexia, or malnutrition. Chronic administration of corticosteroids in rats results in the selective atrophy of type II fast-twitch fibers. Conversely, type I fibers are selectively targeted during experimentally induced thyrotoxicosis.