Changes in immune cell signalling, apoptosis and stress response functions in mice returned from the BION-M1 mission in space

Новоселова, Е. Г.; Лунин, С. М.; Хренов, М. О.; Parfenyuk, Svetlana B.; Новоселова, Т. В.; Шенкман, Борис; Фесенко, Е. Е.

doi:10.1016/j.imbio.2014.10.021

Cited by 36 publications

(29 citation statements)

References 43 publications

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“…Typically, shorter duration experiments than the Validation study show that spaceflight causes atrophy of the immune organs, which is often attributed to an endocrine stress response, although direct effects of microgravity on immune cells in vitro also occur 34 . The greater thymus weights observed in FLT animals relative to GC contrasts to observations from previous, short and long term missions 27,[35][36][37] , but is consistent with findings from other spaceflight experiments. Unlike previous missions, tissues from mice analyzed in the present study were preserved on-orbit, and therefore the animals did not endure the added challenges of a return flight to Earth and ambulation, which can potentially affect gene expression as well as soft tissue weights 38 .…”

Section: Discussionsupporting

confidence: 89%

Validation of a New Rodent Experimental System to Investigate Consequences of Long Duration Space Habitation

Choi

Saravia-Butler²,

Shirazi‐Fard

et al. 2020

Sci Rep

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Animal models are useful for exploring the health consequences of prolonged spaceflight. Capabilities were developed to perform experiments in low earth orbit with on-board sample recovery, thereby avoiding complications caused by return to Earth. For NASA's Rodent Research-1 mission, female mice (ten 32 wk C57BL/6NTac; ten 16 wk C57BL/6J) were launched on an unmanned vehicle, then resided on the International Space Station for 21/22d or 37d in microgravity. Mice were euthanized on-orbit, livers and spleens dissected, and remaining tissues frozen in situ for later analyses. Mice appeared healthy by daily video health checks and body, adrenal, and spleen weights of 37d-flight (FLT) mice did not differ from ground controls housed in flight hardware (GC), while thymus weights were 35% greater in FLT than GC. Mice exposed to 37d of spaceflight displayed elevated liver mass (33%) and select enzyme activities compared to GC, whereas 21/22d-FLT mice did not. FLT mice appeared more physically active than respective Gc while soleus muscle showed expected atrophy. RnA and enzyme activity levels in tissues recovered on-orbit were of acceptable quality. thus, this system establishes a new capability for conducting long-duration experiments in space, enables sample recovery on-orbit, and avoids triggering standard indices of chronic stress.

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Section: Discussionsupporting

confidence: 89%

Validation of a New Rodent Experimental System to Investigate Consequences of Long Duration Space Habitation

Choi

Saravia-Butler²,

Shirazi‐Fard

et al. 2020

Sci Rep

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“…The weight of the thymus in rodents has reportedly decreased [ 7 , 20 ] or remained unchanged [ 3 ] in space experiments. Although the thymus weight among the HCU mice increased, there was no difference in Keratin-5 and Keratin-8 positive epithelial cells of thymi between the HCU mice and the control mice ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Ground-based assessment of JAXA mouse habitat cage unit by mouse phenotypic studies

Shimbo¹,

Kudo

Hamada

et al. 2016

Exp. Anim.

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The Japan Aerospace Exploration Agency developed the mouse Habitat Cage Unit (HCU) for installation in the Cell Biology Experiment Facility (CBEF) onboard the Japanese Experimental Module (“Kibo”) on the International Space Station. The CBEF provides “space-based controls” by generating artificial gravity in the HCU through a centrifuge, enabling a comparison of the biological consequences of microgravity and artificial gravity of 1 g on mice housed in space. Therefore, prior to the space experiment, a ground-based study to validate the habitability of the HCU is necessary to conduct space experiments using the HCU in the CBEF. Here, we investigated the ground-based effect of a 32-day housing period in the HCU breadboard model on male mice in comparison with the control cage mice. Morphology of skeletal muscle, the thymus, heart, and kidney, and the sperm function showed no critical abnormalities between the control mice and HCU mice. Slight but significant changes caused by the HCU itself were observed, including decreased body weight, increased weights of the thymus and gastrocnemius, reduced thickness of cortical bone of the femur, and several gene expressions from 11 tissues. Results suggest that the HCU provides acceptable conditions for mouse phenotypic analysis using CBEF in space, as long as its characteristic features are considered. Thus, the HCU is a feasible device for future space experiments.

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“…Monocytes from the blood also showed altered pro‐ and antiinflammatory cytokine production, increased TLR4 but decreased CD14 expressions, reduced ability to engulf pathogenic Escherichia coli , and an inability to generate an oxidative burst (4, 7‐9). Altered T cell distribution and cytokine production, decreased T cell activation, proliferation, cytotoxic functions, and decreased NKfunctions were also observed (4, 10, 11). This systemic immune dysfunction under microgravity may render hosts more susceptible to pathogenic infections (4, 12‐14).…”

mentioning

confidence: 99%

Simulated microgravity disrupts intestinal homeostasis and increases colitis susceptibility

Li¹,

Shi²,

Zhang³

et al. 2015

The FASEB Journal

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The immune systems can be altered by spaceflight in many aspects, but microgravity-related mucosal immune changes and its clinical significance have not been well studied. The purpose of this study was to investigate whether simulated microgravity influences the intestinal homeostasis and increases the susceptibility to colon inflammation. The hindlimb unloading (HU) mouse model was used to simulate the microgravity condition. Three percent dextran sulfate sodium (DSS) was given to mice to induce colitis. Compared to ground control (Ctrl) mice, the HU ones revealed an impaired intestinal homeostasis and increased susceptibility to DSS-induced colitis. This includes an early-onset, 4-fold expansion of segmented filamentous bacteria (SFB), more than 2-fold decrease in regulatory T (Treg) cell numbers and IL-10 production, ∼2-fold increase in colonic IL-1β expression, 2-fold increase in circulating neutrophils, and colonic neutrophil infiltration. The application of antibiotics ameliorated the Treg and IL-10 reductions but did not significantly dampen neutrophilia and elevated expression of colonic IL-1β. These results indicate that the intestinal microflora and innate immune system both respond to simulated microgravity and together, contribute to the proinflammatory shift in the gut microenvironment. The data also emphasize the necessity for evaluating the susceptibility to inflammatory bowel diseases (IBDs) in distant space travels.

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Changes in immune cell signalling, apoptosis and stress response functions in mice returned from the BION-M1 mission in space

Cited by 36 publications

References 43 publications

Validation of a New Rodent Experimental System to Investigate Consequences of Long Duration Space Habitation

Validation of a New Rodent Experimental System to Investigate Consequences of Long Duration Space Habitation

Ground-based assessment of JAXA mouse habitat cage unit by mouse phenotypic studies

Simulated microgravity disrupts intestinal homeostasis and increases colitis susceptibility

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