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Abstract
Long-duration spaceflight creates a variety of stresses due to the unique environment, which can lead to compromised functioning of the skeletal and immune systems. However, the mechanisms by which organisms respond to this stress remain unclear. The present study aimed to investigate the impact of three different gravitational loadings (microgravity, 1/6 g [lunar gravity], and 1 g) on the behavior, bone, thymus, and spleen of mice housed for 25–35 days in the International Space Station. The bone density reduction under microgravity was mostly recovered by 1 g but only partially recovered by 1/6 g. Both 1 g and 1/6 g suppressed microgravity-induced changes in some osteoblast and osteoclast marker gene expression. Thymus atrophy induced by microgravity was half recovered by both 1 g and 1/6 g, but gene expression changes were not fully recovered by 1/6 g. While no histological changes were observed due to low gravity, alterations in gene expression were noted in the spleen. We found that in bone and thymus, lunar gravity reduced microgravity-induced histological alterations and partially reversed gene expression changes. This study highlighted organ-specific variations in responsiveness to gravity, serving as an animal test for establishing a molecular-level gravity threshold for maintaining a healthy state during future spaceflight.
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1 University of Tsukuba, Laboratory Animal Resource Center in Transborder Medical Research Center, and Department of Anatomy and Embryology, Institute of Medicine, Tsukuba, Japan (GRID:grid.20515.33) (ISNI:0000 0001 2369 4728); University of Tsukuba, College of Medicine, School of Medicine and Health Sciences, Tsukuba, Japan (GRID:grid.20515.33) (ISNI:0000 0001 2369 4728)
2 Institute of Science Tokyo, Department of Cellular Physiological Chemistry, Graduate School of Medical and Dental Sciences, Tokyo, Japan (GRID:grid.20515.33); Research Institute, National Rehabilitation Center for Persons with Disabilities, Department of Rehabilitation for Movement Functions, Saitama, Japan (GRID:grid.419714.e) (ISNI:0000 0004 0596 0617)
3 RIKEN Center for Integrative Medical Sciences, Laboratory for Immune Homeostasis, Yokohama, Japan (GRID:grid.509459.4) (ISNI:0000 0004 0472 0267); Yokohama City University, Immunobiology Laboratory, Graduate School of Medical Life Science, Yokohama, Japan (GRID:grid.268441.d) (ISNI:0000 0001 1033 6139)
4 University of Tsukuba, Laboratory Animal Resource Center in Transborder Medical Research Center, and Department of Anatomy and Embryology, Institute of Medicine, Tsukuba, Japan (GRID:grid.20515.33) (ISNI:0000 0001 2369 4728)
5 University of Tsukuba, Laboratory Animal Resource Center in Transborder Medical Research Center, and Department of Anatomy and Embryology, Institute of Medicine, Tsukuba, Japan (GRID:grid.20515.33) (ISNI:0000 0001 2369 4728); National Institute of Advanced Industrial Science and Technology, Cellular and Molecular Biotechnology Research Institute, Tsukuba, Japan (GRID:grid.208504.b) (ISNI:0000 0001 2230 7538)
6 University of Tsukuba, Laboratory Animal Resource Center in Transborder Medical Research Center, and Department of Anatomy and Embryology, Institute of Medicine, Tsukuba, Japan (GRID:grid.20515.33) (ISNI:0000 0001 2369 4728); University of Tsukuba, Ph.D. Program in Human Biology, School of Integrative and Global Majors, Tsukuba, Japan (GRID:grid.20515.33) (ISNI:0000 0001 2369 4728)
7 University of Tsukuba, Laboratory Animal Resource Center in Transborder Medical Research Center, and Department of Anatomy and Embryology, Institute of Medicine, Tsukuba, Japan (GRID:grid.20515.33) (ISNI:0000 0001 2369 4728); University of Tsukuba, Ph.D. Program in Humanics, School of Integrative and Global Majors, Tsukuba, Japan (GRID:grid.20515.33) (ISNI:0000 0001 2369 4728)
8 Research Institute, National Rehabilitation Center for Persons with Disabilities, Department of Rehabilitation for Movement Functions, Saitama, Japan (GRID:grid.419714.e) (ISNI:0000 0004 0596 0617)
9 Institute of Science Tokyo, Center for Innovative Cancer Treatment, Tokyo, Japan (GRID:grid.419714.e)
10 University of Tsukuba, Laboratory Animal Resource Center in Transborder Medical Research Center, and Department of Anatomy and Embryology, Institute of Medicine, Tsukuba, Japan (GRID:grid.20515.33) (ISNI:0000 0001 2369 4728); ISS/Kibo Experiment, Japan Aerospace Exploration, Mouse Epigenetics Project, Tsukuba, Japan (GRID:grid.20515.33)
11 Gifu University Graduate School of Medicine, Department of Physiology, Gifu, Japan (GRID:grid.256342.4) (ISNI:0000 0004 0370 4927)
12 ISS/Kibo Experiment, Japan Aerospace Exploration, Mouse Epigenetics Project, Tsukuba, Japan (GRID:grid.256342.4); Tokai Gakuin University, Department of Nutrition Management, Gifu, Japan (GRID:grid.420117.1) (ISNI:0000 0000 9437 3801)
13 Human Spaceflight Technology Directorate, JAXA, Space Environment Utilization Center, Tsukuba, Japan (GRID:grid.420117.1)
14 ISS/Kibo Experiment, Japan Aerospace Exploration, Mouse Epigenetics Project, Tsukuba, Japan (GRID:grid.420117.1); Human Spaceflight Technology Directorate, JAXA, Space Environment Utilization Center, Tsukuba, Japan (GRID:grid.420117.1)
15 ISS/Kibo Experiment, Japan Aerospace Exploration, Mouse Epigenetics Project, Tsukuba, Japan (GRID:grid.420117.1); University of Tsukuba, Department of Genome Biology, Transborder Medical Research Center, Institute of Medicine, Tsukuba, Japan (GRID:grid.20515.33) (ISNI:0000 0001 2369 4728)
16 Research Institute, National Rehabilitation Center for Persons with Disabilities, Department of Rehabilitation for Movement Functions, Saitama, Japan (GRID:grid.419714.e) (ISNI:0000 0004 0596 0617); ISS/Kibo Experiment, Japan Aerospace Exploration, Mouse Epigenetics Project, Tsukuba, Japan (GRID:grid.419714.e)
17 RIKEN Center for Integrative Medical Sciences, Laboratory for Immune Homeostasis, Yokohama, Japan (GRID:grid.509459.4) (ISNI:0000 0004 0472 0267); Yokohama City University, Immunobiology Laboratory, Graduate School of Medical Life Science, Yokohama, Japan (GRID:grid.268441.d) (ISNI:0000 0001 1033 6139); ISS/Kibo Experiment, Japan Aerospace Exploration, Mouse Epigenetics Project, Tsukuba, Japan (GRID:grid.268441.d)