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      Development of new experimental platform ‘MARS’—Multiple Artificial-gravity Research System—to elucidate the impacts of micro/partial gravity on mice

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          Abstract

          This Japan Aerospace Exploration Agency project focused on elucidating the impacts of partial gravity (partial g) and microgravity (μ g) on mice using newly developed mouse habitat cage units (HCU) that can be installed in the Centrifuge-equipped Biological Experiment Facility in the International Space Station. In the first mission, 12 C57BL/6 J male mice were housed under μ g or artificial earth-gravity (1  g). Mouse activity was monitored daily via downlinked videos; μ g mice floated inside the HCU, whereas artificial 1  g mice were on their feet on the floor. After 35 days of habitation, all mice were returned to the Earth and processed. Significant decreases were evident in femur bone density and the soleus/gastrocnemius muscle weights of μ g mice, whereas artificial 1  g mice maintained the same bone density and muscle weight as mice in the ground control experiment, in which housing conditions in the flight experiment were replicated. These data indicate that these changes were particularly because of gravity. They also present the first evidence that the addition of gravity can prevent decreases in bone density and muscle mass, and that the new platform ‘MARS’ may provide novel insights on the molecular-mechanisms regulating biological processes controlled by partial gg.

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          Most cited references16

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          Adaptation of Mouse Skeletal Muscle to Long-Term Microgravity in the MDS Mission

          The effect of microgravity on skeletal muscles has so far been examined in rat and mice only after short-term (5–20 day) spaceflights. The mice drawer system (MDS) program, sponsored by Italian Space Agency, for the first time aimed to investigate the consequences of long-term (91 days) exposure to microgravity in mice within the International Space Station. Muscle atrophy was present indistinctly in all fiber types of the slow-twitch soleus muscle, but was only slightly greater than that observed after 20 days of spaceflight. Myosin heavy chain analysis indicated a concomitant slow-to-fast transition of soleus. In addition, spaceflight induced translocation of sarcolemmal nitric oxide synthase-1 (NOS1) into the cytosol in soleus but not in the fast-twitch extensor digitorum longus (EDL) muscle. Most of the sarcolemmal ion channel subunits were up-regulated, more in soleus than EDL, whereas Ca2+-activated K+ channels were down-regulated, consistent with the phenotype transition. Gene expression of the atrophy-related ubiquitin-ligases was up-regulated in both spaceflown soleus and EDL muscles, whereas autophagy genes were in the control range. Muscle-specific IGF-1 and interleukin-6 were down-regulated in soleus but up-regulated in EDL. Also, various stress-related genes were up-regulated in spaceflown EDL, not in soleus. Altogether, these results suggest that EDL muscle may resist to microgravity-induced atrophy by activating compensatory and protective pathways. Our study shows the extended sensitivity of antigravity soleus muscle after prolonged exposition to microgravity, suggests possible mechanisms accounting for the resistance of EDL, and individuates some molecular targets for the development of countermeasures.
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            Effects of spaceflight on innate immune function and antioxidant gene expression.

            Spaceflight conditions have a significant impact on a number of physiological functions due to psychological stress, radiation, and reduced gravity. To explore the effect of the flight environment on immunity, C57BL/6NTac mice were flown on a 13-day space shuttle mission (STS-118). In response to flight, animals had a reduction in liver, spleen, and thymus masses compared with ground (GRD) controls (P < 0.005). Splenic lymphocyte, monocyte/macrophage, and granulocyte counts were significantly reduced in the flight (FLT) mice (P < 0.05). Although spontaneous blastogenesis of splenocytes in FLT mice was increased, response to lipopolysaccharide (LPS), a B-cell mitogen derived from Escherichia coli, was decreased compared with GRD mice (P < 0.05). Secretion of IL-6 and IL-10, but not TNF-alpha, by LPS-stimulated splenocytes was increased in FLT mice (P < 0.05). Finally, many of the genes responsible for scavenging reactive oxygen species were upregulated after flight. These data indicate that exposure to the spaceflight environment can increase anti-inflammatory mechanisms and change the ex vivo response to LPS, a bacterial product associated with septic shock and a prominent Th1 response.
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              Microbial Monitoring of Crewed Habitats in Space—Current Status and Future Perspectives

              Previous space research conducted during short-term flight experiments and long-term environmental monitoring on board orbiting space stations suggests that the relationship between humans and microbes is altered in the crewed habitat in space. Both human physiology and microbial communities adapt to spaceflight. Microbial monitoring is critical to crew safety in long-duration space habitation and the sustained operation of life support systems on space transit vehicles, space stations, and surface habitats. To address this critical need, space agencies including NASA (National Aeronautics and Space Administration), ESA (European Space Agency), and JAXA (Japan Aerospace Exploration Agency) are working together to develop and implement specific measures to monitor, control, and counteract biological contamination in closed-environment systems. In this review, the current status of microbial monitoring conducted in the International Space Station (ISS) as well as the results of recent microbial spaceflight experiments have been summarized and future perspectives are discussed.
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                Author and article information

                Contributors
                shiba.dai@jaxa.jp
                shirakawa.masaki@jaxa.jp
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                7 September 2017
                7 September 2017
                2017
                : 7
                : 10837
                Affiliations
                [1 ]Mouse Epigenetics Project, ISS/Kibo experiment, Japan Aerospace Exploration Agency (JAXA), Tsukuba, Japan
                [2 ]JEM Utilization Center, Human Spaceflight Technology Directorate, JAXA, Tsukuba, Japan
                [3 ]ISNI 0000 0004 0370 4927, GRID grid.256342.4, Department of Physiology, , Gifu University Graduate School of Medicine, ; Gifu, Japan
                [4 ]ISNI 0000 0001 2369 4728, GRID grid.20515.33, Department of Anatomy and Embryology, , Faculty of Medicine, University of Tsukuba, ; Tsukuba, Japan
                [5 ]ISNI 0000 0001 2369 4728, GRID grid.20515.33, Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba, ; Tsukuba, Japan
                [6 ]ISNI 0000 0001 2369 4728, GRID grid.20515.33, Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba, ; Tsukuba, Japan
                [7 ]ISNI 0000 0001 1014 9130, GRID grid.265073.5, Department of Systems BioMedicine, , Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, ; Tokyo, Japan
                [8 ]ISNI 0000 0004 1754 9200, GRID grid.419082.6, Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), ; Tokyo, Japan
                Article
                10998
                10.1038/s41598-017-10998-4
                5589811
                28883615
                671f08af-6037-436d-8f0a-28782040cf18
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 27 June 2017
                : 17 August 2017
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