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The muscle cells, or myofibers, are one of the three multinucleated cell types, along with osteoclasts and cytotrophoblasts. This aspect of skeletal muscle has led to the concept of myonuclear domain, which is defined as the theoretical amount of cytoplasm within a muscle fiber controlled by a single myonucleus. Considering the huge plasticity of skeletal muscle fibers, the myonuclear domain has become one aspect of major interest under situations leading to muscle atrophy (spinal cord isolation and transaction, microgravity, hindlimb suspension and chronic denervation) hypertrophy (synergist ablation and bouts of exercise) and day-to-day wear and tear (age, body size, muscle function and fiber type-related differences). This concept is supported by several studies reporting that changes in muscle fibers' cross-sectional area (CSA) are paralleled by an alteration in the number of myonuclei, maintaining constant the relationship between them. This implies a fairly strict regulation of the myonuclear number that is governed by two opposing mechanisms: the gain of myonuclei by the fusion of muscle stem cells into hypertrophying muscle fibers and the loss of myonuclei by apoptosis/necrosis in atrophying muscle fibers. The aim of this review is to scrutinize the changes in the myonuclear domain in skeletal muscle fibers considering the atrophic and hypertrophic processes, emphasizing the differences between the various methods utilized to achieve these morphological alterations, and the differences between muscle responses according to their phenotype (different function and fiber type composition) and animal age (relevance to sarcopenia). [ABSTRACT FROM AUTHOR]

Objective: The effects of hindlimb unweighting by tail suspension on mice's soleus muscle cross-sectional area (CSA) and myonuclei content were studied. Design: Five groups of male Charles River CD 1 mice (n=10 per group) were assigned to varying hindlimb suspension (HS) periods: control (cont), 1 (1HS), 2 (2HS), 3 (3HS) and 8 (8HS) days. Immediately after the suspension period, the soleus muscles were removed in order to assess morphometry data. The CSA and number of myonuclei were determined in a total of 5011 fibers (1098, 793, 1363, 1281, 1276 fibers for the cont, 1HS, 2HS, 3HS, 8HS groups, respectively) from different areas in the mid-portion region of the soleus muscle, and the CSA per myonucleus ratio was calculated. Results: The results showed that the removing of weight bearing had a negative impact on muscle fiber CSA (1686 ± 516 μm2, 1506 ± 470 μm2, 1235 ± 340 μm2, 1277 ± 412 μm2 and 1075 ± 356 μm2 in the cont, 1HS, 2HS, 3HS and 8HS groups, respectively) and myonuclei number per fiber (1.91 ± 1.17, 1.94 ± 1.30, 1.55 ± 1.01, 1.48 ± 1.00 and 0.83 ± 0.76 in the cont, 1HS, 2HS, 3HS and 8HS groups, respectively). The CSA per myonucleus ratio was 993 ± 522 μm2, 854 ± 443 μm2, 815 ± 374 μm2, 881 ± 442 μm2 and 957 ± 367 μm2 in the cont, 1HS, 2HS, 3HS and 8HS groups, respectively. Thus, there were no significant differences between the control and 8HS groups. Conclusion: The morphological data is consistent with the hypothesis that, despite the muscle fiber atrophy induced by HS, the CSA per myonucleus ratio is apparently maintained, reinforcing the concept of myonuclear domain. [ABSTRACT FROM AUTHOR]