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Bioeffects of Microgravity and Hypergravity on Animals
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Gravity alterations in space cause significant adaptive effects on the human body, including changes to the muscular, skeletal, and vestibular systems. However, multiple factors besides gravity exist in space; therefore, it is difficult to distinguish gravity-related bioeffects from those of the other factors, including radiation. Although everything on the Earth surface is subject to gravity, gravity-induced effects are not explicitly clear. Here, different research methods that have been used in gravity alterations, including parabolic flight, diamagnetic levitation, and centrifuge, are reviewed and compared. The bioeffects that are reported to be associated with altered gravity in animals are summarized, and the potential risks of hypergravity and microgravity are discussed, with a focus on microgravity, which has been studied more extensively. It should be noted that although various microgravity and hypergravity research methods have their limitations, such as the inevitable magnetic field effects in diamagnetic levitation and short duration of parabolic flight, it is evident that ground-based clinical, animal, and cellular experiments that simulate gravity alterations have served as important and necessary complements to space research. These researches not only provide critical and fundamental biological information on the effects of gravity from biomechanics and the biophysical perspectives, but also help in developing future countermeasures for astronauts.
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Bioeffects of Microgravity and Hypergravity on Animals
)
Abstract
Gravity alterations in space cause significant adaptive effects on the human body, including changes to the muscular, skeletal, and vestibular systems. However, multiple factors besides gravity exist in space; therefore, it is difficult to distinguish gravity-related bioeffects from those of the other factors, including radiation. Although everything on the Earth surface is subject to gravity, gravity-induced effects are not explicitly clear. Here, different research methods that have been used in gravity alterations, including parabolic flight, diamagnetic levitation, and centrifuge, are reviewed and compared. The bioeffects that are reported to be associated with altered gravity in animals are summarized, and the potential risks of hypergravity and microgravity are discussed, with a focus on microgravity, which has been studied more extensively. It should be noted that although various microgravity and hypergravity research methods have their limitations, such as the inevitable magnetic field effects in diamagnetic levitation and short duration of parabolic flight, it is evident that ground-based clinical, animal, and cellular experiments that simulate gravity alterations have served as important and necessary complements to space research. These researches not only provide critical and fundamental biological information on the effects of gravity from biomechanics and the biophysical perspectives, but also help in developing future countermeasures for astronauts.
References(121)
E Afshinnekoo, R T Scott, M J MacKay, et al. Fundamental biological features of spaceflight: Advancing the field to enable deep-space exploration. Cell, 2020, 183: 1162-1184.
S Jillings, A Van Ombergen, E Tomilovskaya, et al. Macro- and microstructural changes in cosmonauts’ brains after long-duration spaceflight. Science Advances, 2020, 6: eaaz9488.
D R Roberts, M H Albrecht, H R Collins, et al. Effects of spaceflight on astronaut brain structure as indicated on MRI. New England Journal of Medicine, 2017, 377: 1746-1753.
B R Unsworth, P I Lelkes. Growing tissues in microgravity. Nature Medicine, 1998, 4: 901-907.
K A Kirsch, L Rocker, O H Gauer, et al. Venous pressure in man during weightlessness. Science, 1984, 225: 218-219.
J Man, T Graham, G Squires-Donelly, et al. The effects of microgravity on bone structure and function. NPJ Microgravity, 2022, 8: 9.
M Stavnichuk, N Mikolajewicz, T Corlett, et al. A systematic review and meta-analysis of bone loss in space travelers. NPJ Microgravity, 2020, 6: 13.
A G Lee, T H Mader, C R Gibson, et al. Spaceflight associated neuro-ocular syndrome (SANS) and the neuro-ophthalmologic effects of microgravity: A review and an update. NPJ Microgravity, 2020, 6: 7.
L F Zhang, A R Hargens. Spaceflight-induced intracranial hypertension and visual impairment: Pathophysiology and countermeasures. Physiological Reviews, 2018, 98: 59-87.
K J Fitzelle, J Z Kiss. Restoration of gravitropic sensitivity in starch-deficient mutants of Arabidopsis by hypergravity. Journal of Experimental Botany, 2001, 52: 265-275.
V Pletser. European aircraft parabolic flights for microgravity research, applications and exploration: A review. Reach, 2016, 1: 11-19.
M Shelhamer. Parabolic flight as a spaceflight analog. Journal of Applied Physiology, 2016, 120: 1442-1448.
K Guevorkian, J M Valles Jr. Swimming paramecium in magnetically simulated enhanced, reduced, and inverted gravity environments. Proceedings of the National Academy of Sciences, 2006, 103: 13051-13056.
A Qian, D Yin, P Yang, et al. Development of a ground-based simulated experimental platform for gravitational biology. IEEE Transactions on Applied Superconductivity, 2009, 19(2): 42-46.
G Carmeliet, R Bouillon. The effect of microgravity on morphology and gene expression of osteoblasts in vitro. The FASEB Journal, 1999, 13: S129-134.
H M Lu, X L Lu, J H Zhai, et al. Effects of large gradient high magnetic field (LG-HMF) on the long-term culture of aquatic organisms: Planarians example. Bioelectromagnetics, 2018, 39: 428-440.
R Fournier, R E Harrison. Strategies for studying bone loss in microgravity. Reach, 2020, 17-20: 100036.
L I Kakurin, V I Lobachik, V M Mikhailov, et al. Antiorthostatic hypokinesia as a method of weightlessness simulation. Aviation, Space, and Environmental Medicine, 1976, 47: 1083-1086.
S S Laurie, B R Macias, J T Dunn, et al. Optic disc edema after 30 days of strict head-down tilt bed rest. Ophthalmology, 2019, 126: 467-468.
J L Becker, G R Souza. Using space-based investigations to inform cancer research on Earth. Nature Reviews Cancer, 2013, 13: 315-327.
T Könemann, U Kaczmarczik, A Gierse, et al. Concept for a next-generation drop tower system. Advances in Space Research, 2015, 55: 1728-1733.
P von Kampen, U Kaczmarczik, H J Rath. The new drop tower catapult system. Acta Astronautica, 2006, 59: 278-283.
X Zhang, L Yuan, W Wu, et al. Some key technics of drop tower experiment device of National Microgravity Laboratory (China) (NMLC). Science in China Series E, 2005, 48: 305-316.
J Z Kiss. Plant biology in reduced gravity on the moon and mars. Plant Biology (Stuttg), 2014, 16: 12-17.
D Selva, D Krejci. A survey and assessment of the capabilities of cubesats for earth observation. Acta Astronautica, 2012, 74: 50-68.
F Ferranti, M Del Bianco, C Pacelli. Advantages and limitations of current microgravity platforms for space biology research. Applied Sciences, 2020, 11: 68.
E Tomilovskaya, T Shigueva, D Sayenko, et al. Dry immersion as a ground-based model of microgravity physiological effects. Frontiers in Physiology, 2019, 10: 284.
K J Hackney, L L Ploutz-Snyder. Unilateral lower limb suspension: Integrative physiological knowledge from the past 20 years (1991—2011). European Journal of Applied Physiology, 2011, 112: 9-22.
F A Oluwafemi, A Neduncheran. Analog and simulated microgravity platforms for life sciences research: Their individual capacities, benefits and limitations. Advances in Space Research, 2022, 69: 2921-2929.
J Bonnefoy, S Ghislin, J Beyrend, et al. Gravitational experimental platform for animal models, a new platform at ESA’s terrestrial facilities to study the effects of micro- and hypergravity on aquatic and rodent animal models. International Journal of Molecular Sciences, 2021, 22: 2961.
C De Cesari, I Barravecchia, O V Pyankova, et al. Hypergravity activates a pro-angiogenic homeostatic response by human capillary endothelial cells. International Journal of Molecular Sciences, 2020, 21: 2354.
A Acharya, S Brungs, Y Lichterfeld, et al. Parabolic, flight-induced, acute hypergravity and microgravity effects on the beating rate of human cardiomyocytes. Cells, 2019, 8: 352.
N Gueguinou, C Huin-Schohn, M Bascove, et al. Could spaceflight-associated immune system weakening preclude the expansion of human presence beyond Earth’s orbit? Journal of Leukocyte Biology, 2009, 86: 1027-1038.
F E Garrett-Bakelman, M Darshi, S J Green, et al. The NASA twins study: A multidimensional analysis of a year-long human spaceflight. Science, 2019, 364: eaau8650.
G Sonnenfeld. The immune system in space and microgravity. Medicine and Science in Sports and Exercise, 2002, 34: 2021-2027.
J H Bradley, R Stein, B Randolph, et al. T cell resistance to activation by dendritic cells requires long-term culture in simulated microgravity. Life Sciences in Space Research, 2017, 15: 55-61.
S K Mehta, M L Laudenslager, R P Stowe, et al. Multiple latent viruses reactivate in astronauts during space shuttle missions. Brain, Behavior, and Immunity, 2014, 41: 210-217.
B Crucian, R Stowe, S Mehta, et al. Immune system dysregulation occurs during short duration spaceflight on board the space shuttle. Journal of Clinical Immunology, 2013, 33: 456-465.
G Spielmann, N Agha, H Kunz, et al. B cell homeostasis is maintained during long-duration spaceflight. Journal of Applied Physiology, 2019, 126: 469-476.
S K Mehta, R P Stowe, A H Feiveson, et al. Reactivation and shedding of cytomegalovirus in astronauts during spaceflight. Journal of Infectious Diseases, 2000, 182: 1761-1764.
J J W A van Loon. Centrifuges for microgravity simulation. The reduced gravity paradigm. Frontiers in Astronomy and Space Sciences, 2016, 3: 21.
U Stervbo, T Roch, T Kornprobst, et al. Gravitational stress during parabolic flights reduces the number of circulating innate and adaptive leukocyte subsets in human blood. PloS One, 2018, 13: e0206272.
M Feuerecker, B Feuerecker, S Matzel, et al. Five days of head-down-tilt bed rest induces noninflammatory shedding of L-selectin. Journal of Applied Physiology, 2013, 115: 235-242.
J B Boonyaratanakornkit, A Cogoli, C F Li, et al. Key gravity-sensitive signaling pathways drive T cell activation. FASEB Journal, 2005, 19: 2020-2022.
R P Stowe, D L Pierson, A D Barrett. Elevated stress hormone levels relate to Epstein-Barr virus reactivation in astronauts. Psychosomatic Medicine, 2001, 63: 891-895.
C L Benjamin, R P Stowe, L St John, et al. Decreases in thymopoiesis of astronauts returning from space flight. JCI Insight, 2016, 1: e88787.
I Kaur, E R Simons, V A Castro, et al. Changes in monocyte functions of astronauts. Brain, Behavior, and Immunity, 2005, 19: 547-554.
M Schwarzenberg, P Pippia, M A Meloni, et al. Signal transduction in tlymphocytes: A comparison of the data from space, the free fall machine and the random positioning machine. Advances in Space Research, 1999, 24: 793-800.
G Tascher, M Gerbaix, P Maes, et al. Analysis of femurs from mice embarked on board BION-M1 biosatellite reveals a decrease in immune cell development, including B cells, after 1 wk of recovery on Earth. FASEB Journal, 2019, 33: 3772-3783.
E M Martinez, M C Yoshida, T L Candelario, et al. Spaceflight and simulated microgravity cause a significant reduction of key gene expression in early T-cell activation. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 2015, 308: R480-8.
S A Hwang, B Crucian, C Sams, et al. Post-spaceflight (STS-135) mouse splenocytes demonstrate altered activation properties and surface molecule expression. PloS One, 2015, 10: e0124380.
C Fonte, S Kaminski, A Vanet, et al. Socioenvironmental stressors encountered during spaceflight partially affect the murine TCR-beta repertoire and increase its self-reactivity. FASEB Journal, 2019, 33: 896-908.
N Nabavi, A Khandani, A Camirand, et al. Effects of microgravity on osteoclast bone resorption and osteoblast cytoskeletal organization and adhesion. Bone, 2011, 49: 965-974.
N Rucci, A Rufo, M Alamanou, et al. Modeled microgravity stimulates osteoclastogenesis and bone resorption by increasing osteoblast RANKL/OPG ratio. Journal of Cellular Biochemistry, 2007, 100: 464-473.
M Zayzafoon, W E Gathings, J M McDonald. Modeled microgravity inhibits osteogenic differentiation of human mesenchymal stem cells and increases adipogenesis. Endocrinology, 2004, 145: 2421-2432.
R Saxena, G Pan, J M McDonald. Osteoblast and osteoclast differentiation in modeled microgravity. Annals of the New York Academy of Sciences, 2007, 1116: 494-498.
J M Spatz, M N Wein, J H Gooi, et al. The WNT inhibitor sclerostin is up-regulated by mechanical unloading in osteocytes in vitro. Journal of Biological Chemistry, 2015, 290: 16744-16758.
T Lang, A LeBlanc, H Evans, et al. Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. Journal of Bone and Mineral Research, 2004, 19: 1006-1012.
C J Hernandez, A Gupta, T M Keaveny. A biomechanical analysis of the effects of resorption cavities on cancellous bone strength. Journal of Bone and Mineral Research, 2006, 21: 1248-1255.
S L Bonnick, L Shulman. Monitoring osteoporosis therapy: Bone mineral density, bone turnover markers, or both? American Journal of Medicine, 2006, 119: S25-31.
S M Smith, M E Wastney, K O O’Brien, et al. Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the MIR space station. Journal of Bone and Mineral Research, 2005, 20: 208-218.
S M Smith, M Heer, L C Shackelford, et al. Bone metabolism and renal stone risk during international space station missions. Bone, 2015, 81: 712-720.
J D Sibonga, H J Evans, H G Sung, et al. Recovery of spaceflight-induced bone loss: Bone mineral density after long-duration missions as fitted with an exponential function. Bone, 2007, 41: 973-978.
R Dana Carpenter, A D LeBlanc, H Evans, et al. Long-term changes in the density and structure of the human hip and spine after long-duration spaceflight. Acta Astronautica, 2010, 67: 71-81.
M Hughes-Fulford, M L Lewis. Effects of microgravity on osteoblast growth activation. Experimental Cell Research, 1996, 224: 103-109.
M Gioia, A Michaletti, M Scimeca, et al. Simulated microgravity induces a cellular regression of the mature phenotype in human primary osteoblasts. Cell Death Discovery, 2018, 4: 59.
A Cazzaniga, J A M Maier, S Castiglioni. Impact of simulated microgravity on human bone stem cells: New hints for space medicine. Biochemical and Biophysical Research Communications, 2016, 473: 181-186.
V E Meyers, M Zayzafoon, J T Douglas, et al. RhoA and cytoskeletal disruption mediate reduced osteoblastogenesis and enhanced adipogenesis of human mesenchymal stem cells in modeled microgravity. Journal of Bone and Mineral Research, 2005, 20: 1858-1866.
L F Hu, J B Li, A R Qian, et al. Mineralization initiation of MC3T3-E1 preosteoblast is suppressed under simulated microgravity condition. Cell Biology International, 2015, 39(4): 364-372.
M J Patel, W Liu, M C Sykes, et al. Identification of mechanosensitive genes in osteoblasts by comparative microarray studies using the rotating wall vessel and the random positioning machine. Journal of Cellular Biochemistry, 2007, 101: 587-599.
R L Summers, D S Martin, J V Meck, et al. Mechanism of spaceflight-induced changes in left ventricular mass. The American Journal of Cardiology, 2005, 95: 1128-1130.
J M Scott, L B Dolan, L Norton, et al. Multisystem toxicity in cancer: Lessons from NASA’s countermeasures program. Cell, 2019, 179: 1003-1009.
R L Hughson, A Helm, M Durante. Heart in space: Effect of the extraterrestrial environment on the cardiovascular system. Nature Reviews Cardiology, 2018, 15: 167-180.
T Anzai, M A Frey, A Nogami. Cardiac arrhythmias during long-duration spaceflights. Journal of Arrhythmia, 2014, 30: 139-149.
M A Perhonen, F Franco, L D Lane, et al. Cardiac atrophy after bed rest and spaceflight. Journal of Applied Physiology, 2001, 91: 645-653.
C S Leach, P C Johnson. Influence of spaceflight on erythrokinetics in man. Science, 1984, 225: 216-218.
G Trudel, N Shahin, T Ramsay, et al. Hemolysis contributes to anemia during long-duration space flight. Nature Medicine, 2022, 28: 59-62.
S H Patel, A C D’Lugos, E R Eldon, et al. Impact of acetaminophen consumption and resistance exercise on extracellular matrix gene expression in human skeletal muscle. American Journal of Physiology Regulatory, Integrative and Comparative Physiology, 2017, 313: R44-R50.
S Trappe, D Costill, P Gallagher, et al. Exercise in space: Human skeletal muscle after 6 months aboard the international space station. Journal of Applied Physiology, 2009, 106: 1159-1168.
P A Tesch, H E Berg, D Bring, et al. Effects of 17-day spaceflight on knee extensor muscle function and size. European Journal of Applied Physiology, 2005, 93: 463-468.
D Sandona, J F Desaphy, G M Camerino, et al. Adaptation of mouse skeletal muscle to long-term microgravity in the MDS mission. PloS One, 2012, 7(3): e33232.
R H Fitts, S W Trappe, D L Costill, et al. Prolonged space flight-induced alterations in the structure and function of human skeletal muscle fibres. Journal of Physiology, 2010, 588: 3567-3592.
S W Trappe, T A Trappe, G A Lee, et al. Comparison of a space shuttle flight (STS-78) and bed rest on human muscle function. Journal of Applied Physiology, 2001, 91: 57-64.
A LeBlanc, C Lin, L Shackelford, et al. Muscle volume, MRI relaxation times (T2), and body composition after spaceflight. Journal of Applied Physiology, 2000, 89: 2158-2164.
R Gopalakrishnan, K O Genc, A J Rice, et al. Muscle volume, strength, endurance, and exercise loads during 6-month missions in space. Aviation Space and Environmental Medicine, 2010, 81: 91-102.
G R Adams, V J Caiozzo, K M Baldwin. Skeletal muscle unweighting: Spaceflight and ground-based models. Journal of Applied Physiology, 2003, 95: 2185-2201.
P Kortebein, A Ferrando, J Lombeida, et al. Effect of 10 days of bed rest on skeletal muscle in healthy older adults. Journal of the American Medical Association, 2007, 297: 1772-1774.
T A Trappe, N A Burd, E S Louis, et al. Influence of concurrent exercise or nutrition countermeasures on thigh and calf muscle size and function during 60 days of bed rest in women. Acta Physiologica, 2007, 191: 147-159.
J Carriot, I Mackrous, K E Cullen. Challenges to the vestibular system in space: How the brain responds and adapts to microgravity. Frontiers in Neural Circuits, 2021, 15: 760313.
S J Wood, W H Paloski, J B Clark. Assessing sensorimotor function following iss with computerized dynamic posturography. Aerospace Medicine and Human Performance, 2015, 86: A45-A53.
V Jain, S J Wood, A H Feiveson, et al. Diagnostic accuracy of dynamic posturography testing after short-duration spaceflight. Aviation Space and Environmental Medicine, 2010, 81: 625-631.
M D Ross. Changes in ribbon synapses and rough endoplasmic reticulum of rat utricular macular hair cells in weightlessness. Acta Oto-Laryngologica, 2000, 120: 490-499.
J Carriot, I Mackrous, K E Cullen. Challenges to the vestibular system in space: How the brain responds and adapts to microgravity. Frontiers in Neural Circuits, 2021, 15: 760313.
G C Demontis, M M Germani, E G Caiani, et al. Human pathophysiological adaptations to the space environment. Frontiers in Physiology, 2017, 8: 547.
C Papaseit, N Pochon, J Tabony. Microtubule self-organization is gravity-dependent. Proceedings of the National Academy of Sciences of the United States of America, 2000, 97: 8364-8368.
M Janmaleki, M Pachenari, S M Seyedpour, et al. Impact of simulated microgravity on cytoskeleton and viscoelastic properties of endothelial cell. Scientific Reports, 2016, 6: 32418.
Z Q Dai, R Wang, S K Ling, et al. Simulated microgravity inhibits the proliferation and osteogenesis of rat bone marrow mesenchymal stem cells. Cell Proliferation, 2007, 40: 671-684.
S J Pardo, M J Patel, M C Sykes, et al. Simulated microgravity using the Random Positioning Machine inhibits differentiation and alters gene expression profiles of 2T3 preosteoblasts. American Journal of Physiology: Cell Physiology, 2005, 288(6): C1211-1221.
N Gueguinou, M Bojados, M Jamon, et al. Stress response and humoral immune system alterations related to chronic hypergravity in mice. Psychoneuroendocrinology, 2012, 37(1): 137-147.
T Koyama, C Kimura, M Hayashi, et al. Hypergravity induces ATP release and actin reorganization via tyrosine phosphorylation and RhoA activation in bovine endothelial cells. European Journal of Physiology, 2009, 457: 711-719.
L Morbidelli, N Marziliano, V Basile, et al. Effect of hypergravity on endothelial cell function and gene expression. Microgravity Science and Technology, 2008, 21: 135-140.
A Cogoli, A Tschopp, P Fuchs-Bislin. Cell sensitivity to gravity. Science, 1984, 225: 228-230.
E M Woodcock, P Girvan, J Eckert, et al. Measuring intracellular viscosity in conditions of hypergravity. Biophysical Journal, 2019, 116: 1984-1993.
G Ciofani, L Ricotti, J Rigosa, et al. Hypergravity effects on myoblast proliferation and differentiation. Journal of Bioscience and Bioengineering, 2012, 113: 258-261.
A Tschopp, A Cogoli. Hypergravity promotes cell proliferation. Experientia, 1983, 39: 1323-1329.
Y Huang, Z Q Dai, S K Ling, et al. Gravity, a regulation factor in the differentiation of rat bone marrow mesenchymal stem cells. Journal of Biomedical Science, 2009, 16: 87.
T Tominari, R Ichimaru, K Taniguchi, et al. Hypergravity and microgravity exhibited reversal effects on the bone and muscle mass in mice. Scientific Reports, 2019, 9: 6614.
V Bouet, R J Wubbels, H A de Jong, et al. Behavioural consequences of hypergravity in developing rats. Brain Research: Developmental Brain Research, 2004, 153: 69-78.
N Kawao, H Morita, K Obata, et al. The vestibular system is critical for the changes in muscle and bone induced by hypergravity in mice. Physiological Reports, 2016, 4: e12979.
G G Genchi, F Cialdai, M Monici, et al. Hypergravity stimulation enhances PC12 neuron-like cell differentiation. BioMed Research International, 2015: 748121.
C Bosco. Adaptive response of human skeletal muscle to simulated hypergravity condition. Acta Physiologica Scandinavica, 1985, 124: 507-513.
D Santucci, G Corazzi, N Francia, et al. Neurobehavioural effects of hypergravity conditions in the adult mouse. Neuroreport, 2000, 11: 3353-3356.
C Alauzet, L Cunat, M Wack, et al. Hypergravity disrupts murine intestinal microbiota. Scientific Reports, 2019, 9: 9410.
C Liu, G Zhong, Y Zhou, et al. Alteration of calcium signalling in cardiomyocyte induced by simulated microgravity and hypergravity. Cell Proliferation, 2020, 53: e12783.
Y Liu, D M Zhu, D M Strayer, et al. Magnetic levitation of large water droplets and mice. Advances in Space Research, 2010, 45: 208-213.
Y Lv, Y Fan, X Tian, et al. The anti-depressive effects of ultra-high static magnetic field. Journal of Magnetic Resonance Imaging, 2022, 56: 354-365.
X Tian, Y Lv, Y Fan, et al. Safety evaluation of mice exposed to 7.0-33.0 T high-static magnetic fields. Journal of Magnetic Resonance Imaging, 2021, 53: 1872-1884.
X Tian, C Wang, B Yu, et al. 9.4 T static magnetic field ameliorates imatinib mesylate-induced toxicity and depression in mice. European Journal of Nuclear Medicine and Molecular Imaging, 2023, 50: 314-327.
X Tian, D Wang, S Feng, et al. Effects of 3.5-23.0 t static magnetic fields on mice: A safety study. Neuroimage, 2019, 199: 273-280.
B Yu, C Song, C L Feng, et al. Effects of gradient high-field static magnetic fields on diabetic mice. Zoological Research, 2023, 44: 249-258.
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