Chopard A, Lecunff M, Danger R, Lamirault G, Bihouee A, Teusan R, Jasmin BJ, Marini JF, Leger JJ. Large-scale mRNA analysis of female skeletal muscles during 60 days of bed rest with and without exercise or dietary protein supplementation as countermeasures. Physiol Genomics 38: 291-302, 2009. First published May 26, 2009 doi:10.1152/physiolgenomics.00036.2009.-Microgravity has a dramatic impact on human physiology, illustrated in particular, with skeletal muscle impairment. A thorough understanding of the mechanisms leading to loss of muscle mass and structural disorders is necessary for defining efficient clinical and spaceflight countermeasures. We investigated the effects of long-term bed rest on the transcriptome of soleus (SOL) and vastus lateralis (VL) muscles in healthy women (BRC group, n ϭ 8), and the potential beneficial impact of protein supplementation (BRN group, n ϭ 8) and of a combined resistance and aerobic training (BRE group, n ϭ 8). Gene expression profiles were obtained using a customized microarray containing 6,681 muscles-relevant genes. A two-class statistical analysis was applied on 2,103 genes with consolidated expression in BRC, BRN, and BRE groups. We identified 472 and 207 mRNAs whose expression was modified in SOL and VL from BRC group, respectively. Further clustering analysis, identifying relevant biological mechanisms and pathways, reported five main subclusters. Three are composed of upregulated mRNAs involved mainly in nucleic acid and protein metabolism, and two made up of downregulated transcripts encoding components involved in energy metabolism. Exercise countermeasure demonstrated drastic compensatory effects, decreasing the number of differentially expressed mRNAs by 89 and 96% in SOL and VL, respectively. In contrast, nutrition countermeasure had moderate effects and decreased the number of differentially-expressed transcripts by 40 and 25% in SOL and VL. Together, these data present a systematic, global and comprehensive view of the adaptive response of female muscle to long-term atrophy.skeletal muscle fiber; atrophy; microgravity; microarray; leucine SKELETAL MUSCLE IS ONE OF the most affected tissues in disuse situations since it can exhibit large structural and functional adaptations, depending on changes in the levels of imposed mechanical constraints (1). Neuromuscular activity is decreased by hypokinesia and hypodynamia, as well by microgravity environment resulting in skeletal muscle atrophy (35). Space exploration and interplanetary travel requires that humans be confronted with extended durations of space environment and weightlessness. From a few days in space (with the Mercury, Gemini, and Apollo-Soyouz programs), to several months in a space station (with Skylab, MIR, and the actual ISS), disuse-induced muscle atrophy and impairment is a biomedical challenge and a focus point of space sciences in studying the deleterious effects of microgravity (1,27,35).Human bed rest (BR), a ground-based model, provides an opportunity to understand the components of musc...

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