Morphological and molecular aspects of immobilization-induced muscle atrophy in rats at different stages of postnatal development: the role of autophagy

• Published in: Journal of applied physiology (1985) 2016-09, Vol.121 (3), p.646-660
• Main Authors: Foresto, Camila Silva, Paula-Gomes, Sílvia, Silveira, Wilian Assis, Graça, Flávia Aparecida, Kettelhut, Isis do Carmo, Gonçalves, Dawit Albieiro Pinheiro, Mattiello-Sverzut, Ana Claudia
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological; Aging; Animals; Animals, Newborn; Autophagy; Female; Hindlimb Suspension; Molecules; Morphology; Muscle, Skeletal - pathology; Muscle, Skeletal - physiopathology; Muscular Atrophy - physiopathology; Muscular system; Phosphorylation; Rats; Rats, Wistar; Rodents
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00687.2015

Muscle loss occurs following injury and immobilization in adulthood and childhood, which impairs the rehabilitation process; however, far fewer studies have been conducted analyzing atrophic response in infants. This work investigated first the morphological and molecular mechanisms involved in immobilization-induced atrophy in soleus muscles from rats at different stages of postnatal development [i.e., weanling (WR) and adult (AR) rats] and, second, the role of autophagy in regulating muscle plasticity during immobilization. Hindlimb immobilization for 10 days reduced muscle mass and fiber cross-sectional area, with more pronounced atrophy in WR, and induced slow-to-fast fiber switching. These effects were accompanied by a decrease in markers of protein synthesis and an increase in autophagy. The ubiquitin (Ub)-ligase MuRF1 and the ubiquitinated proteins were upregulated by immobilization in AR while the autolyzed form of μ-calpain was increased in WR. To further explore the role of autophagy in muscle abnormalities, AR were concomitantly immobilized and treated with colchicine, which blocks autophagosome-lysosome fusion. Colchicine-treated immobilized muscles had exacerbated atrophy and presented degenerative features. Despite Igf1/Akt signaling was downregulated in immobilized muscles from both age groups, Foxo1 and 4 phosphorylation was increased in WR. In the same group of animals, Foxo1 acetylation and Foxo1 and 4 content was increased and decreased, respectively. Our data show that muscle disorders induced by 10-day-immobilization occur in both age-dependent and -independent manners, an understanding that may optimize treatment outcomes in infants. We also provide further evidence that the strong inhibition of autophagy may be ineffective for treating muscle atrophy.