Animal Biology Program

Experiments

Each animal biology experiment that Space Biology supports is designed to build our understanding of how the novel environment(s) of spaceflight affect complex multicellular organisms at the molecular, physiological, and systemic levels. Below are some examples of?Space Biology-funded Animal research projects that are still in progress or have recently been completed.

Novel Facility Developed for Testing Moon and Mars Effects

In a first-of-its-kind study, investigators developed and tested an experimental analog facility designed to re-create the partial gravity environments of the Moon and Mars. Using rats as human analogs, the quadrupedal unloading model involved partial-suspension of the animals with a harness system. The facility induced similar muscle disuse atrophy and bone mineral density reductions seen in traditional hind limb unloading studies that have been employed to study the effects of microgravity.

Being able to simulate Moon-like gravity conditions on Earth is particularly challenging given that we aren’t on the Moon. Researchers in this investigation devised and demonstrated a novel system to mimic the partial gravity effects of these deep space environments by rigging a harness system to partially unload the limbs at several levels of unloading. The study showed after 2 weeks of partial weight bearing at 20%, 40%, or 70% of normal loading that the musculoskeletal health of the animals experienced decreased trabecular bone density, hind limb muscle mass, and impaired muscle function as reduced-gravity analogue facility is well suited for long-duration studies.? It can be used to assess impacts of re-loading, as well as testing any countermeasures that could potentially be used for deep space missions. For humans to explore deeper into space, it will be important to understand the effects of long-term exposure to partial gravity environments, such as those on the Moon or Mars.

Mortreux M, Nagy JA, Ko FC, Bouxsein ML, Rutkove SB.?A novel partial gravity ground-based analogue for rats via quadrupedal unloading.?J Appl Physiol (1985). 2018 Mar 22.


Spaceflight Changes Protein Expression in the Brain

Space Biology-funded researchers Dr. Michael Pecaut and Dr. Xiao Wen Mao at Loma Linda University recently published an article in International Journal of Molecular Sciences (IF 3.687) reporting the results of a proteomic analysis of brains of mice flown in space for 13 days on STS-135. Proteomic analysis identifies the proteins present in tissues, providing a direct look at cell metabolism and function. The study reported in the article was the first to examine changes in brain proteins induced by spaceflight, and found significant changes related to neuron structure and metabolic function that could, in time, lead to injury and neurodegeneration. This suggests that spaceflight affects the brain negatively at a cellular level, and that countermeasures to protect brain function may be needed.

Mao XW, Sandberg LB, Gridley DS, Herrmann EC, Zhang G, Raghavan R, Zubarev RA, Zhang B, Stodieck LS, Ferguson VL, Bateman TA, Pecaut MJ.?Proteomic analysis of mouse brain subjected to spaceflight.?Int J Mol Sci. 2018 Dec 20;20(1):E7.?https://www.ncbi.nlm.nih.gov/pubmed/30577490
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Short Durations of Daily Loading Prevent Some Detrimental Effects of Simulated Microgravity

A major risk facing astronauts on long-duration spaceflight missions is bone loss, and the accompanying increase in risk of bone fracture upon return to gravity. Astronauts exposed to microgravity for six months can lose as much as 10% of their bone mineral density, and this bone loss may not be recovered upon return to gravity. Effective countermeasures that prevent bone loss in microgravity are still needed.

A study recently published by a research team including Dr. Bloomfield, a NASA Space Biology-supported researcher at Texas A&M University, provides a piece of the puzzle. The study measured bone volume and structure in mice exposed to four weeks of simulated microgravity, some of which were exposed to normal gravity conditions for 75 minutes a day, three out of every four days. Microgravity was simulated using the technique of hindlimb unloading, in which mice are suspended by their tails so that their forelimbs bear their entire body weight. Mice in both simulated microgravity groups lost overall bone mass compared to control mice that were not exposed to simulated microgravity. However, unlike the mice exposed to simulated gravity continuously, the mice exposed to simulated microgravity, but also to short periods of normal gravity, did not lose spongy (cancellous) bone mass from their femurs.

Though daily exposure to normal gravity did not “rescue” the mice in this study from all deleterious effects of simulated microgravity, it prevented some – bringing researchers one step closer to understanding the complex web of biological processes linking microgravity and bone loss, and one step closer to a solution.

Bokhari RS, Metzger CE, Allen M, Bloomfield S.?Daily Acute Bouts of Weightbearing During Hindlimb Unloading Mitigate Disuse-Induced Deficits in Cancellous Bone.?Gravitational and Space Research. 2018 Dec 17; 6(2).


Experimental Drug Treatment Prevents Bone Loss in Mars Simulation

As NASA prepares for the Journey to Mars it is particularly challenging to understand and test the effects of the partial gravity environment on humans before actually going there. At approximately one third of Earth’s gravity there is nowhere on our home planet that can approximate the partial gravity of Mars. To address that challenge, some resourceful Space Biology researchers have developed a unique partial-gravity model to test rodents in a Moon and Mars analog simulation. To investigate the effects on bones that have been subjected to partial gravity mice were assigned to one of four loading groups: normal weight-bearing controls, or weight-bearing at 20%, 40%, or 70% of normal. Mice in each experimental group received a treatment previously shown to be effective in preventing bone loss in a ground-based unloading experiment – sclerostin antibody. This experiment was primarily designed to further test the effectiveness of sclerostin in mice exposed to different levels of unloading that astronauts would encounter on long-duration terrestrial spaceflight mission.

Results of this investigation suggest that greater weight bearing leads to greater benefits of the sclerostin treatment on bone mass, particularly the trabecular bone. Altogether, these results demonstrate the efficacy of sclerostin antibody therapy in preventing astronaut bone loss during terrestrial solar system exploration.

Spatz JM, Ellman R, Cloutier AM, Louis L, van Vliet M, Dwyer D, Stolina M, Ke HZ, Bouxsein ML.??Sclerostin antibody inhibits skeletal deterioration in mice exposed to partial weight-bearing.?Life Sci Space Res. 2017 Feb;12:32-8. Epub 2017 Jan 12.
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Effects of Spaceflight on Gastrointestinal Microbiota in Mice:?Mechanisms and Impact on Multi-System Physiology (RR-7)

Five integrated projects will examine the impact of the space environment on the population structure of the intestinal microbiota of mice, and how multiple physiological systems involving the gastrointestinal (GI), immune, metabolic, circadian, and sleep systems, known to be affected by the microbiota, are impacted by the space environment. The proposed studies will elucidate mechanisms underlying interactions between GI, immune, metabolic, and sleep functions and specifically the role of the microbiota in these interactions. The impact of this study extends beyond understanding the mechanisms at play in the unique stresses of spaceflight. Results from the proposed RR-7 investigation have the potential for guiding development of dysbiosis-targeted interventions for disorders in all of these systems.

Organism: Mouse
Principal Investigator: Fred Turek, Ph.D., Northwestern University
Instrument: Rodent Habitat

Rodent Research-7:?Inner space

Current research tells us that changes in the gut microbiome (the collective populations of microbial species living in the gastrointestinal tract) affect areas of physiology in the heart, the immune system, and gastro-intestinal health. The Rodent Research 7 mission will examine, from a whole-animal perspective, how diet and circadian rhythm impact the health of mice and the microbiome of the gut, from individual tissues and physiological response down to the cellular and molecular level. The experiment will seek to understand on a molecular level how changes in circadian rhythm affect the immune system and metabolome (how the body metabolizes food and waste).

Rodent Research-9:?Multisystem studies

Mice provide an important animal model that has been used by NASA scientists to increase our understanding of how spaceflight affects the mammalian musculoskeletal, cardiovascular, immune, and central nervous systems. On the recent?Rodent Research?mission, three Space Biology investigations shared mice flown to the ISS to characterize how microgravity impacts these systems during extended stays in space. A major objective of one of these ongoing investigations is to determine how long-duration spaceflight effects vascular function and structure in the central nervous system, specifically in response to spaceflight-induced changes in fluid pressure. Another important goal of these experiments is to characterize the impact of oxidative stress within the eye on vascular remodeling in the retina, as well as on the function of the blood retinal barrier; factors that could potentially contribute to visual impairment. A final objective is to determine how long-duration spaceflight impacts knee and hip joint degradation. The researchers conducting these investigations are currently investigating biological changes in these mice, as well as their recovery from spaceflight, now that they have returned to Earth.

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Fruit Fly Lab-3 (FFL-3): Does Spaceflight Alter the Virulence of a Natural Parasite of Drosophila?

Drosophila melanogaster, the fruit fly, has been used extensively to study biological processes, including genetics and physiology. Experiments using this model organism have generated useful information that had provided helpful insights for both human physiology and disease. One important area of study is fruit fly immunity. Fruit flies have an innate immune system similar to that of humans, which acts as the “first responder” to defend an organism from initial infection by a foreign pathogen. NASA-funded studies of immune cells have shown that spaceflight alters immune function.

The FFL-3 mission studies the impact of spaceflight on host/pathogen dynamics, with fruit fly larva acting as the host organism, and a natural parasite of the flies,?Leptopilina?wasp larva, as the pathogen. These wasps lay their eggs into the fly larvae, which induce a fly larval innate immune response against the wasp larvae and eggs, similar to a response to bacterial infection. The experiment has three main objectives. Based on measuring the amount of fly survival against wasp survival, the first objective is to characterize whether the host innate immunity will protect the fly larvae or if the wasp infection process will “defeat” the immune response. The second objective will characterize how the space environment affects the fruit fly’s anti-parasitic immune response to the wasp pathogen.? The third objective will determine if the parasitic virulence of the space-cultured wasps is different from ground control wasps. The results of this investigation will provide important knowledge of how long-duration spaceflight impacts a key immune response mechanism and pathogen infection. This may lead to greater understanding of how the spaceflight environment alters human innate immunity and pathogen interactions.

Extreme Survival

Green tardigrade.

Experiments designed to narrow down key stress pathways may help us understand the critical stress response mechanisms that maintain life in space.

A new Animal Biology study at NASA will examine the omics and molecular biology of cellular adaptions to the extremes of space. Using comparative transcriptomics, genomics, and proteomics coupled with reverse genetics, this new flight experiment seeks to identify genes that respond to and are required for tardigrades to survive different stress conditions. Investigators will examine both immediate and long-term, multigenerational changes in gene expression in tardigrades cultured onboard the International Space Station.

Tardigrades are microscopic, multicellular animals that can live for decades without food or water, and survive temperature extremes from near absolute zero to well above the boiling point of water. Tardigrades have been known to survive a number of abiotic stresses, including desiccation, freezing and boiling temperatures, intense ionizing radiation, and extremes in pressure—including the vacuum of outer space.

One day these experiments may lead to the development of drought- and temperature-resistant crops and new methods for stabilizing sensitive pharmaceuticals and other biological materials.

Additional Resources

Search NASA Task Book

To learn more about current and upcoming research projects in the NASA Space Biology program, search the?Task Book: Biological and Physical Sciences Division and Human Research Program. Our online database of research projects includes project descriptions, annual research results, research impacts, and a listing of publications resulting from this NASA-funded research.

Life Sciences Data Archive

A searchable archive of NASA Life Sciences research is available at the?Life Sciences Data Archive.

GeneLab Data Repository

Experiments that explore the molecular response of terrestrial biology to spaceflight have generated vast amounts of genomics data that are now publicly available for?download from GeneLab.