Animal Biology Program
Check out the recent publications from participating NASA scientists, Principal Investigators, and contributors from universities and labs around the world:
Manian, V., Orozco-Sandoval, J., Diaz-Martinez, V., Janwa, H., & Agrinsoni, C. (2022). Detection of Target Genes for Drug Repurposing to Treat Skeletal Muscle Atrophy in Mice Flown in Spaceflight. Genes, 13(3), 473.
Sattgast, L. H., Wong, C.P., Olson, D.A., Branscum, A.J., Iwaniec, U.T. and Turner, R.T. (2022). Effects of Subthermoneutral Housing on Bone in Female C57BL/6J Mice. The FASEB journal, 36. doi:https://doi.org/10.1096/fasebj.2022.36.S1.R4016.
Siamwala, J. H., Macias, B. R., Healey, R., Bennett, B., & Hargens, A. R. (2022). Spaceflight-Associated Vascular Remodeling and Gene Expression in Mouse Calvaria. Frontiers in Physiology, 13. doi:10.3389/fphys.2022.893025.
Animal Studies (Immunology)
Spaceflight and simulated microgravity conditions increase virulence of Serratia marcescens in the Drosophila melanogaster infection model. Gilbert R, Torres ML, Clemens R, Hateley S, Hosamani R, Wade W, Bhattacharya S. npj Microgravity. 2020 Feb 4;6(1):4. (Bhattacharya, NNX13AN38G and NNX15AB42G).
Serratia marcescens (strain Db11) was significantly more lethal to Drosophila melanogaster after growth on the International Space Station than ground-based controls, but the increased virulence phenotype of S. marcescens did not persist after the bacterial cultures were passaged on the ground.
Spaceflight impairs antigen-specific tolerance induction in vivo and increases inflammatory cytokines.
Chang, T. T., Spurlock, S. M., Candelario, T. L., Grenon, S. M., & Hughes-Fulford, M. (2015). FASEB J. DOI:10.1096/fj.15-275073
Post-Spaceflight (STS-135) Mouse Splenocytes Demonstrate Altered Activation Properties and Surface Molecule Expression.
Hwang, S. A., Crucian, B., Sams, C., Actor, J. K., & (Pecaut). (2015). PLoS One, 10(5), e0124380. DOI:10.1371/journal.pone.0124380
Toll mediated infection response is altered by gravity and spaceflight in Drosophila Taylor, K., Kleinhesselink, K., George, M. D., Morgan, R., Smallwood, T., Hammonds, A. S., . . . Kimbrell, D. A. (2014). PLoS One (Vol. 9, pp. e86485). United States.
Stem Cell Health and Tissue Regeneration in Microgravity.
Stem Cells Dev. 2014 Dec;23 Suppl 1:73-8. DOI: 10.1089/scd.2014.0408.
Blaber E, Sato K, Almeida EA.
Select item 250110754.
Changes in mouse thymus and spleen after return from the STS-135 mission in space. Gridley, D. S., Mao, X. W., Stodieck, L. S., Ferguson, V. L., Bateman, T. A., Moldovan, M., . . . Pecaut, M. J. (2013). PLoS One, 8(9), e75097. DOI:10.1371/journal.pone.0075097
Innate immune responses of Drosophila melanogaster are altered by spaceflight.
Marcu, O., Lera, M. P., Sanchez, M. E., Levic, E., Higgins, L. A., Shmygelska, A., . . . Bhattacharya, S. (2011). PLoS One, 6(1), e15361. DOI:10.1371/journal.pone.0015361
Animal Studies (Musculoskeletal)
Partial weight-bearing in female rats: Proof of concept in a Martian-gravity analog. Semple C, Riveros D, Nagy JA, Rutkove SB, Mortreux M.
Front Physiol. 2020 Apr 3;11:302. (Rutkove, NNX16AL36G)
This pilot study represents the ﬁrst experiment designed to understand the muscular disuse associated with a partial reduction in mechanical loading in female rats, and the ﬁrst step needed to develop successful mitigating strategies.
Dietary countermeasure mitigates simulated spaceflight-induced osteopenia in mice. Steczina S, Tahimic CGT, Pendleton M, M'Saad O, Lowe M, Alwood JS, Halloran BP, Globus RK, Schreurs AS. Sci Rep. 2020 Apr 16;10(1):6484. (SB NPP and SLSTP)
This study tested the Dried Plum (DP) diet for the prevention of bone loss in mice following exposure to simulated spaceflight, combining microgravity (by hindlimb unloading) and radiation exposure. The DP diet was effective at preventing most decrements in bone micro-architectural and mechanical properties due to hindlimb unloading alone and simulated spaceflight, in addition to showing that the DP diet can protect osteoprogenitors from impairments resulting from simulated microgravity.
Molecular muscle experiment: Hardware and operational lessons for future astrobiology space experiments. Pollard AK, Gaffney CJ, Deane CS, Balsamo M, Cooke M, Ellwood RA, Hewitt JE, Mierzwa BE, Mariani A, Vanapalli SA, Etheridge T, Szewczyk NJ.
Astrobiology. 2020 Apr 8. [Epub ahead of print] (Vanapalli, NNX15AL16G)
This is a methods paper that describes the hardware selection and validation, in addition to the ground-based experiment scientific validation testing.
Effects of propranolol on bone, white adipose tissue, and bone marrow adipose tissue in mice housed at room temperature or thermoneutral temperature. Turner RT, Philbrick KA, Wong CP, Gamboa AR, Branscum AJ, Iwaniec UT.
Front Endocrinol (Lausanne). 2020 Mar 17;11:117. (Turner, 80NSSC19K0430)
New findings from this study help us understand why growing mice housed at room temperature (22 C) differ in body composition compared to mice housed at warmer temperatures (32 C). Animals were treated with propranolol (a beta-blocker). Results indicated that the sympathetic nervous system is involved in the temperature-associated differences in the amounts and types of fat tissue through the body.
Dose-dependent skeletal deficits due to varied reductions in mechanical loading in rats. Ko FC, Mortreux M, Riveros D, Nagy JA, Rutkove SB, Bouxsein ML.
npj Microgravity. 2020 May 18;6(1):15. (Rutkove, NNX16AL36G)
Results of this partial gravity analogue study suggest that the rat model of partial weight bearing (PWB) leads to trabecular bone deterioration that is progressive and generally proportional to the degree of PWB, with minimal effects on cortical bone.
Maintenance of near normal bone mass and architecture in lethally irradiated female mice following adoptive transfer with as few as 750 purified hematopoietic stem cells. Deyhle RT Jr, Wong CP, Martin SA, McDougall MQ, Olson DA, Branscum AJ, Menn SA, Iwaniec UT, Hamby DM, Turner RT. Radiat Res. 2019 Mar 14. [Epub ahead of print] (Turner, NNX12AL24G)
The goal of this research was to establish an approach for reconstituting bone marrow using small numbers of purified donor-derived hematopoietic stem cells (HSCs) without negatively affecting bone metabolism. Adoptive transfer of wild-type hematopoietic stem cells into irradiated transgenic (radiation sensitive) mice showed normal gene (Kit) expression in bone marrow. These findings provide strong evidence for efficient engraftment with purified HSCs after lethal TBI with minimal collateral damage to bone. This approach will be useful for investigating mechanisms by which hematopoietic lineage cells regulate bone metabolism.
Dried plum diet protects from bone loss caused by ionizing radiation.
Schreurs, A. S., Shirazi-Fard, Y., Shahnazari, M., Alwood, J. S., Truong, T. A., Tahimic, C. G., . . . Globus, R. K. (2016). Sci Rep, 6, 21343. DOI:10.1038/srep213
Spaceflight-induced vertebral bone loss in ovariectomized rats is associated with increased bone marrow adiposity and no change in bone formation.
Keune, J. A., Philbrick, K. A., Branscum, A. J., Iwaniec, U. T., & Turner, R. T. (2016). npj Microgravity, 2, 16016.
Effects of Hindlimb Unloading and Ionizing Radiation on Skeletal Muscle Resistance Artery Vasodilation and Its Relation to Cancellous Bone in Mice.
Prisby, R. D., Alwood, J. S., Behnke, B. J., Stabley, J. N., McCullough, D. J., Ghosh, P., . . . Delp, M. D. (2015).
J Appl Physiol (1985), jap.00423.02015. DOI:10.1152/japplphysiol.00423.2015
Effects of Spaceflight on Bone Microarchitecture in the Axial and Appendicular Skeleton in Growing Ovariectomized Rats.
Keune, J. A., Branscum, A. J., Iwaniec, U. T., & Turner, R. T. (2015). Sci Rep, 5, 18671. DOI:10.1038/srep18671
Ionizing Radiation Stimulates Expression of Pro-Osteoclastogenic Genes in Marrow and Skeletal Tissue.
Alwood J.S., Shahnazari M., Chicana B., Schreurs A.S., Kumar A., Bartolini A., Shirazi-Fard Y., Globus R.K.
J Interferon Cytokine Res. 2015 Jun;35(6):480-7. DOI: 10.1089/jir.2014.0152.
Epub 2015 Mar 3. PubMed PMID: 25734366; PubMed Central PMCID: PMC4490751.
Mechanical loading causes site-specific anabolic effects on bone following exposure to ionizing radiation.
Bone. 2015 Dec;81:260-9. DOI: 10.1016/j.bone.2015.07.019.
Shirazi-Fard Y, Alwood JS, Schreurs AS, Castillo AB, Globus RK.
Epub 2015 Jul 18. PubMed PMID: 26191778.
Masticatory muscles of mouse do not undergo atrophy in space.
Philippou, A., Minozzo, F. C., Spinazzola, J. M., Smith, L. R., Lei, H., Rassier, D. E., & Barton, E. R. (2015). FASEB J. DOI:10.1096/fj.14-267336
Effects of Skeletal Unloading on the Vasomotor Properties of the Rat Femur Principal Nutrient Artery.
Prisby, R. D., Behnke, B. J., Allen, M. R., & Delp, M. D. (2015). J Appl Physiol (1985), jap.00576.02014. DOI:10.1152/japplphysiol.00576.2014
Mechanical unloading of bone in microgravity reduces mesenchymal and hematopoietic stem cell-mediated tissue regeneration.
Blaber, E. A., Dvorochkin, N., Torres, M. L., Yousuf, R., Burns, B. P., Globus, R. K., & Almeida, E. A. (2014). Stem Cell Res, 13(2), 181-201. DOI:10.1016/j.scr.2014.05.005
Microgravity induces pelvic bone loss through osteoclastic activity, osteocytic osteolysis, and osteoblastic cell cycle inhibition by CDKN1a/p21.
Blaber, E. A., Dvorochkin, N., Lee, C., Alwood, J. S., Yousuf, R., Pianetta, P., . . . Almeida, E. A. (2013). PLoS One, 8(4), e61372. DOI:10.1371/journal.pone.0061372
Fifteen days of microgravity causes growth in calvaria of mice.
Zhang, B., Cory, E., Bhattacharya, R., Sah, R., & Hargens, A. R. (2013). Bone, 56(2), 290-295. DOI:10.1016/j.bone.2013.06.009
Low-dose, ionizing radiation and age-related changes in skeletal microarchitecture.
lwood, J. S., Kumar, A., Tran, L. H., Wang, A., Limoli, C. L., & Globus, R. K. (2012). Journal of Aging Research, 2012.
Animal Studies (Cardiovascular)
Apollo Lunar Astronauts Show Higher Cardiovascular Disease Mortality: Possible Deep Space Radiation Effects on the Vascular Endothelium.
Delp, M. D., Charvat, J. M., Limoli, C. L., Globus, R. K., & Ghosh, P. (2016). Apollo Lunar Astronauts Show Higher Cardiovascular Disease Mortality: Possible Deep Space Radiation Effects on the Vascular Endothelium. Sci Rep, 6, 29901. DOI:10.1038/srep29901
Effects of spaceflight and ground recovery on mesenteric artery and vein constrictor properties in mice.
Behnke, B. J., Stabley, J. N., McCullough, D. J., Davis, R. T., 3rd, Dominguez, J. M., 2nd, Muller-Delp, J. M., & Delp, M. D. (2013). FASEB J, 27(1), 399-409. DOI:10.1096/fj.12-218503
Spaceflight reduces vasoconstrictor responsiveness of skeletal muscle resistance arteries in mice.
Stabley, J. N., Dominguez, J. M., 2nd, Dominguez, C. E., Mora Solis, F. R., Ahlgren, J., Behnke, B. J., . . . Delp, M. D. (2012). J Appl Physiol (1985), 113(9), 1439-1445. DOI:10.1152/japplphysiol.00772.2012
Animal Studies (Remaining Systems)
Validation of a new Rodent experimental System to investigate consequences of Long Duration Space Habitation. Choi, S. Y., Saravia-Butler, A., Shirazi-Fard, Y., Leveson-Gower, D., Stodieck, L. S., Cadena, S. M., ... & Globus, R. K. (2020). Scientific Reports, 10(1), 1-17.
This experiment studies the RR-1 rodent tissues to look for signs of stress. 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), FLT mice displayed elevated liver mass (33%) and select enzyme activities compared to GC, whereas 21/22d-FLT mice did not.
NASA GeneLab platform utilized for biological response to space radiation in animal models. McDonald JT, Stainforth R, Miller J, Cahill T, da Silveira WA, Rathi KS, Hardiman G, Taylor D, Costes SV, Chauhan V, Meller R, Beheshti A. Cancers (Basel). 2020 Feb 7;12(2):E381.
This paper provided a summary of how the GeneLab's rich database of omics experiments with animal models can be used to generate novel hypotheses to better understand human health risks from GCR exposures.
Ankyrin Is An Intracellular Tether for TMC Mechanotransduction Channels. Tang, Y. Q., Lee, S. A., Rahman, M., Vanapalli, S. A., Lu, H., & Schafer, W. R. Neuron. 2020. (Vanapalli, NNX15AL16G)
Using the model organism C. elegans this study has identified specific proteins (TMC and ankyrin) involved in the process of detecting force and transmitting it to nerves They found that the GFP tagged TMC-1 proteins were activated in the ‘touch’ neurons located on the worm’s nose, which indicate that TMC-1 is required in these neurons for nose-touch sensation. They also found a similar response for the proteins found in muscles of the body wall.
Calbindin expression in adult vestibular epithelia. Prins TJ, Myers ZA, Saldate JJ, Hoffman LF. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2020 Apr 29. [Epub ahead of print] (Hoffman, NNX13AL99G)
This study examined the cellular structure of the inner ear. The objective was to determine where calcium-binding proteins are expressed on the surfaces of the utricles and cristae, which contain hair cells that help our bodies sense the orientation of our heads. Although appearing to be located at the same sites, by sophisticated computational analysis and statistics, the investigators determined differences in their distribution.
Tart Cherry Increases Lifespan in Caenorhabditis elegans by Altering Metabolic Signaling Pathways. Jayarathne, S., Ramalingam, L., Edwards, H., Vanapalli, S. A., & Moustaid-Moussa, N. (2020). Nutrients, 12(5), 1482. (Vanapalli, NNX15AL16G)
Study findings indicate that daily dietary supplementation of tart cherry extract (TCE) confers healthspan benefits in C. elegans through enhanced mitochondrial function and reduced oxidative stress, mainly via the DAF-16 pathway.
Behavior of mice aboard the International Space Station. Ronca AE, Moyer EL, Talyansky Y, Lowe M, Padmanabhan S, Choi S, Gong C, Cadena SM, Stodieck L, and Globus RK. Scientific Reports – special issue on Gravitational Biology and Space Medicine, in press. (Funding was provided by the NASA Ames Research Center Space Biology Program, Rodent Research Project, and Center Directors Fund)
This paper presents the analysis of expert review of the circling, or ‘race tracking’ behavior observed in space flown mice during video observations aboard the ISS. The coordinated circling behavior appeared to be age-dependent, with only the younger mice exhibiting the race tracking in space. Study authors present several possible explanations for their observations and posits their approach yields a useful analog for understanding human responses to spaceflight.
Spaceflight Activates Lipotoxic Pathways in Mouse Liver.
Jonscher, K. R., Alfonso-Garcia, A., Suhalim, J. L., Orlicky, D. J., Potma, E. O., Ferguson, V. L., . . . Pecaut, M. J. (2016). PLoS One, 11(4), e0152877. DOI:10.1371/journal.pone.0152877
Neural response in vestibular organ of Helix aspersa to centrifugation and re-adaptation to normal gravity.
Popova, Y., & Boyle, R. (2015). J Comp Physiol A Neuroethol Sens Neural Behav Physiol. DOI:10.1007/s00359-015-1003-x
The effect of spaceflight on mouse olfactory bulb volume, neurogenesis, and cell death indicates the protective effect of novel environment.
Latchney, S.E...Mao, X.W…Eisch, A. (2014). Journal of Applied Physiology, 116(12):1593-604. DOI: 10.1152/japplphysiol.01174.2013
Microgravity alters the expression of salivary proteins.
Mednieks, M., Khatri, A., Rubenstein, R., Burleson, J. A., & Hand, A. R. (2014). Oral Health Dent Manag, 13(2), 211-216
Biological and metabolic response in STS-135 space-flown mouse skin.
Mao, X. W., Pecaut, M. J., Stodieck, L. S., Ferguson, V. L., Bateman, T. A., Bouxsein, M. L., & Gridley, D. S. (2014). Free Radic Res, 48(8), 890-897. DOI:10.3109/10715762.2014.920086