Network Analysis of Skeletal Muscle During Spaceflight in Male Mice

Context: The unloading associated with spaceflight results in the rapid loss of bone and muscle tissue thereby affecting functionality. These are two of the most concerning physiologic changes that occur in space and could limit long-term occupation in space. Thus, a better understanding of the mechanisms of changes to bone and muscle could lead to development of improved therapies to counteract both spaceflight and terrestrial-based bone and muscle dysfunction.Methods: Here we used a non-biased, stringent, deep sequencing (96 million paired end reads targeting 100 bp read length) assay to examine genomic networks altered by spaceflight in the quadriceps (n=4/group). Specifically, 9 week old C57BL/6 male mice were housed on the International Space Station or at Kennedy Space Center for approximately four weeks (n=10/group). Results: 14,228 genes (70% of whole mouse genome) met the cut-off criteria and the data sets were mapped to an average of ~76% of the whole mouse genome. Of these, 840 genes met the t-test criteria, p\u3c0.05. Canonical networks linked to EIF2 signaling, calcium ion signaling, and oxidative stress response were significantly enriched by the differentially expressed genes. A comprehensive energy deprivation was indicated as functions related to protein synthesis and degradation, lipid synthesis and oxidation, and ATP hydrolysis were inhibited, and mitochondrial dysfunction was activated.Conclusions: This is the first time that skeletal muscle changes have been studied in male mice during spaceflight, and these data add important new findings to changes that occur to the musculoskeletal system in male mice during spaceflight. In orthopaedic trauma, many patients spend prolonged periods non-weight bearing and can experience significant muscle atrophy as a result. The networks analyzed in this work may prove to be targets for future therapies to counter this atrophy