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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 181 records · Page 10
All sourcesNASA NTRSDOE OSTI
NASA NTRS2012

Spaceflight Effects and Molecular Responses in the Mouse Eye: Observations After Shuttle Mission STS-133

Microgravity-induced cephalad fluid shift and radiation exposure are some of the stressors seen in space exploration. Ocular changes leading to visual impairment in astronauts are of occupational health relevance. Therefore, we analyzed the effects of space flight in the eyes of mice. Six mice were assigned to Flight (FLT), Animal enclosure Module (AEM), or vivarium (VIV) group, respectively. Mice were sacrificed at 1, 5 or 7 days after landing from space. One eye was used for histological and immunohistoche-mistry analysis and the other eye for gene expression profiling. 8-OHdG and caspase-3 immunoreactivity were increased in the retina in FLT samples at return(R+1) compared to AEM/VIV groups, and decreased at day 7 (R+7). beta-amyloid was seen in the nerve fibers at the post-laminar region of the optic nerve in the flight samples (R+7). In addition, oxidative and cellular stress response genes were upregulated in the retina of FLT samples upon landing, and decreased by R+7. According to the results, a reversible molecular damage may occur in the retina of mice exposed to spaceflight followed by protective cellular response.

Prospero-Ponce, Claudia↗
NASA NTRS2013

Spaceflight and the Mouse Eye: Results from Experiments on Shuttle Missions STS-133 and STS-135

Vision alterations associated with globe flattening, chorodial folds and papilledema, shown in some crew members returning from long duration missions. Hypothesis: Ocular neuroanatomical changes observed in the VIIP syndrome are accompanied by retinal changes at the molecular and cellular level that may affect retinal health and physiology. Objective: Investigate evidence of ocular (retinal) changes associated with spaceflight: (1) histological markers of cellular death and damage (2) molecular markers of oxidative stress (3) gene expression markers of stress

Zanello, Susana B.↗
NASA NTRS2016

Analysis of Adult Female Mouse (Mus musculus) Group Behavior on the International Space Station (ISS)

As interest in long duration effects of space habitation increases, understanding the behavior of model organisms living within the habitats engineered to fly them is vital for designing, validating, and interpreting future spaceflight studies. A handful of papers have previously reported behavior of mice and rats in the weightless environment of space. The Rodent Research Hardware and Operations Validation (Rodent Research-1; RR1) utilized the Rodent Habitat (RH) developed at NASA Ames Research Center to fly mice on the ISS (International Space Station). Ten adult (16-week-old) female C57BL/6 mice were launched on September 21st, 2014 in an unmanned Dragon Capsule, and spent 37 days in microgravity. Here we report group behavioral phenotypes of the RR1 Flight (FLT) and environment-matched Ground Control (GC) mice in the Rodent Habitat (RH) during this long-duration flight. Video was recorded for 33 days on the ISS, permitting daily assessments of overall health and well-being of the mice, and providing a valuable repository for detailed behavioral analysis. We previously reported that, as compared to GC mice, RR1 FLT mice exhibited the same range of behaviors, including eating, drinking, exploration, self- and allo-grooming, and social interactions at similar or greater levels of occurrence. Overall activity was greater in FLT as compared to GC mice, with spontaneous ambulatory behavior, including organized 'circling' or 'race-tracking' behavior that emerged within the first few days of flight following a common developmental sequence, and comprised the primary dark cycle activity persisting throughout the remainder of the experiment. Participation by individual mice increased dramatically over the course of the flight. Here we present a detailed analysis of 'race-tracking' behavior in which we quantified: (1) Complete lap rotations by individual mice; (2) Numbers of collisions between circling mice; (3) Lap directionality; and (4) Recruitment of mice into a group phenotype. This analysis contributes to the first NASA long-duration study of rodent behavior, providing evidence for the emergence of a distinctive, organized group behavior unique to the weightless space environment.

Behavior in Space↗
NASA NTRS2016

Change in Mouse Bone Turnover in Response to Microgravity on RR-1

Mechanical unloading during spaceflight is known to adversely affect mammalian physiology. Our previous studies using the Animal Enclosure Module on short duration Shuttle missions enabled us to identify a deficit in stem cell based-tissue regeneration as being a significant concern for long-duration spaceflight. Specifically, we found that mechanical unloading in microgravity resulted in inhibition of differentiation of mesenchymal and hematopoietic stem cells in the bone marrow compartment. Also, we observed overexpression of a cell cycle arrest molecule, CDKN1ap21, in osteoprecursor cells on the bone surface, chondroprogenitors in the articular cartilage, and in myofibers attached to bone tissue. Specifically in bone tissue during both short (15-day) and long (30-day) microgravity experiments, we observed significant loss of bone tissue and structure in both the pelvis and the femur. After 15-days of microgravity on STS-131, pelvic ischium displayed a 6.23 decrease in bone fraction (p0.005) and 11.91 decrease in bone thickness (p0.002). Furthermore, during long-duration spaceflight we observed onset of an accelerated aging-like phenotype and osteoarthritic disease state indicating that stem cells within the bone tissue fail to repair and regenerate tissues in a normal manner, leading to drastic tissue alterations in response to microgravity. The Rodent Research Hardware System provides the capability to investigate these effects during long-duration experiments on the International Space Station. During the Rodent Research-1 mission 10 16-week-old female C57Bl6J mice were exposed to 37-days of microgravity. All flight animals were euthanized and frozen on orbit for future dissection. Ground (n10) and vivarium controls (n10) were housed and processed to match the flight animal timeline. During this study we collected pelvis, femur, and tibia from all animal groups to test the hypothesis that stem cell-based tissue regeneration is significantly altered after 37-days of spaceflight. To do this, we will analyze differences in bone morphometric parameters using MicroCT. The pelvis, femur, and tibia are key in supporting and distributing weight under normal conditions. Therefore, we expect to see altered remodeling in flight animals in response to microgravity with respect to ground controls. In combination with histomorphometry, these results will help elucidate the complex mechanisms underlying bone tissue maintenance and stem cell regeneration.

bone↗
NASA NTRS2016

Transgenic Mouse Model for Reducing Oxidative Damage in Bone

Bone loss can occur due to many challenges such age, radiation, microgravity, and Reactive Oxygen Species (ROS) play a critical role in bone resorption by osteoclasts (Bartell et al. 2014). We hypothesize that suppression of excess ROS in skeletal cells, both osteoblasts and osteoclasts, regulates skeletal growth and remodeling. To test our hypothesis, we used transgenic mCAT mice which overexpress the human anti-oxidant catalase gene targeted to the mitochondria, the main site for endogenous ROS production. mCAT mice have a longer life-span than wildtype controls and have been used to study various age-related disorders. To stimulate remodeling, 16 week old mCAT mice or wildtype mice were exposed to treatment (hindlimb-unloading and total body-irradiation) or sham treatment conditions (control). Tissues were harvested 2 weeks later for skeletal analysis (microcomputed tomography), biochemical analysis (gene expression and oxidative damage measurements), and ex vivo bone marrow derived cell culture (osteoblastogenesis and osteoclastogenesis). mCAT mice expressed the transgene and displayed elevated catalase activity in skeletal tissue and marrow-derived osteoblasts and osteoclasts grown ex vivo. In addition, when challenged with treatment, bone tissues from wildtype mice showed elevated levels of malondialdehyde (MDA), indicating oxidative damage) whereas mCAT mice did not. Correlation analysis revealed that increased catalase activity significantly correlated with decreased MDA levels and that increased oxidative damage correlated with decreased percent bone volume (BVTV). In addition, ex-vivo cultured osteoblast colony growth correlated with catalase activity in the osteoblasts. Thus, we showed that these transgenic mice can be used as a model to study the relationship between markers of oxidative damage and skeletal properties. mCAT mice displayed reduced BVTV and trabecular number relative to wildtype mice, as well as increased structural model index in the cancellous tibia. Treatment caused bone loss in wildtype mice, as expected. Treatment also caused deficits in microarchitecture of mCAT mice, although less severe than wildtype mice in some parameters (percent bone volume, structural model index and cortical area). In conclusion, our results indicate that endogenous ROS signaling in both osteoblast and osteoclast lineage cells contributes to skeletal growth and remodeling, and quenching oxidative damage could play a role in bone loss prevention.

transgenic mice↗
NASA NTRS2016

Changes in Mouse Bone Turnover in Response to Microgravity

Mechanical unloading during spaceflight is known to adversely affect mammalian physiology. Our previous studies using the Animal Enclosure Module on short duration Shuttle missions enabled us to identify a deficit in stem cell based-tissue regeneration as being a significant concern for long-duration spaceflight. Specifically, we found that mechanical unloading in microgravity resulted in inhibition of differentiation of mesenchymal and hematopoietic stem cells in the bone marrow compartment. Also, we observed overexpression of a cell cycle arrest molecule, CDKN1a/p21, in osteoprecursor cells on the bone surface, chondroprogenitors in the articular cartilage, and in myofibers attached to bone tissue. Specifically in bone tissue during both short (15-day) and long (30-day) microgravity experiments, we observed significant loss of bone tissue and structure in both the pelvis and the femur. After 15-days of microgravity on STS-131, pelvic ischium displayed a 6.23% decrease in bone fraction (p=0.005) and 11.91% decrease in bone thickness (p=0.002). Furthermore, during long-duration spaceflight we observed onset of an accelerated aging-like phenotype and osteoarthritic disease state indicating that stem cells within the bone tissue fail to repair and regenerate tissues in a normal manner, leading to drastic tissue alterations in response to microgravity. The Rodent Research Hardware System provides the capability to investigate these effects during long-duration experiments on the International Space Station. During the Rodent Research-1 mission 10 16-week-old female C57Bl/6J mice were exposed to 37-days of microgravity. All flight animals were euthanized and frozen on orbit for future dissection. Ground (n=10) and vivarium controls (n=10) were housed and processed to match the flight animal timeline. During this study we collected pelvis, femur, and tibia from all animal groups to test the hypothesis that stem cell-based tissue regeneration is significantly altered after 37-days of spaceflight. To do this, we will analyze differences in bone morphometric parameters using MicroCT. The pelvis, femur, and tibia are key in supporting and distributing weight under normal conditions. Therefore, we expect to see altered remodeling in flight animals in response to microgravity with respect to ground controls. In combination with histomorphometry, these results will help elucidate the complex mechanisms underlying bone tissue maintenance and stem cell regeneration.

microgravity↗
NASA NTRS2017

Mouse Behavior on ISS: The Emergence of a Distinctive, Organized Group Circling Behavior Unique to Spaceflight

As interest in long duration effects of space habitation increases, understanding the behavior of model organisms living within the habitats engineered to fly them is vital for designing, validating, and interpreting future spaceflight studies. Only a handful of papers have previously reported behavior of mice and rats in the weightless environment of space (Andreev-Andrievskiy, et al., 2013; Cancedda et al., 2012; Ronca et al., 2008). The Rodent Research Hardware and Operations Validation Mission (Rodent Research-1; RR1) utilized the Rodent Habitat (RH) developed at NASA Ames Research Center to fly mice on the ISS. Ten adult (16-week-old) female C57BL6J mice were launched on September 21st, 2014 in an unmanned Dragon Capsule, and spent 37 days in flight. Here we report group behavioral phenotypes of the RR1 Flight (FLT) and environment-matched Ground Control (GC) mice in the RH during this long duration flight. Video was recorded for 34 days on the ISS, permitting daily assessments of overall health and well being of the mice, and providing a valuable repository for detailed behavioral analysis. As compared to GC mice, RR1 FLT mice exhibited the same range of behaviors, including eating, drinking, exploration, self- and allogrooming, and social interactions at similar or greater levels of occurrence. Overall activity was greater in FLT as compared to GC mice, with spontaneous ambulatory behavior, including organized circling or race-tracking behavior that emerged within the first few days of flight following a common developmental sequence, comprising the primary dark cycle activity of FLT mice. Circling participation by individual mice persisted throughout the mission. Analysis of group behavior over mission days revealed recruitment of mice into the group phenotype, coupled with decreasing numbers of collisions between circling mice. This analysis provides insights into the behavior of mice in microgravity, and clear evidence for the emergence of a distinctive, organized group behavior unique to the weightless space environment. Supported by the NASA Rodent Research Project, Space Biology Program, and Space Life Sciences Training Program.

spaceflight↗
NASA NTRS2017

Mouse Behavior on ISS: The Emergence of Distinctive, Organized Group Circling Behavior Unique to Spaceflight

As interest in long duration effects of space habitation increases, understanding the behavior of model organisms living within the habitats engineered to fly them is vital for designing, validating, and interpreting future spaceflight studies. Only a handful of papers have previously reported behavior of mice and rats in the weightless environment of space (Andreev-Andrievskiy, et al., 2013; Cancedda et al., 2012; Ronca et al., 2008). The Rodent Research Hardware and Operations Validation Mission (Rodent Research-1; RR1) utilized the Rodent Habitat (RH) developed at NASA Ames Research Center to fly mice on the ISS. Ten adult (16-week-old) female C57BL6J mice were launched on September 21st, 2014 in an unmanned Dragon Capsule, and spent 37 days in flight. Here we report group behavioral phenotypes of the RR1 Flight (FLT) and environment-matched Ground Control (GC) mice in the RH during this long duration flight. Video was recorded for 34 days on the ISS, permitting daily assessments of overall health and well being of the mice, and providing a valuable repository for detailed behavioral analysis. As compared to GC mice, RR1 FLT mice exhibited the same range of behaviors, including eating, drinking, exploration, self- and allogrooming,and social interactions at similar or greater levels of occurrence. Overallactivity was greater in FLT as compared to GC mice, with spontaneous ambulatory behavior, including organized circling or race-tracking behavior that emerged within thefirst few days of flight following a common developmental sequence, comprising theprimary dark cycle activity of FLT mice. Circling participation by individual micepersisted throughout the mission. Analysis of group behavior over mission days revealed recruitment of mice into the group phenotype, coupled with decreasing numbers of collisions between circling mice. This analysis provides insights into the behavior of mice in microgravity, and clear evidence for the emergence of a distinctive,organized group behavior unique to the weightless space environment.

mice↗
NASA NTRS2017

Spaceflight Activates Autophagy Programs and the Proteasome in Mouse Liver

Increased oxidative stress is an unavoidable consequence of exposure to the space environment. Our previous studies showed that mice exposed to space for 13.5 days had decreased glutathione levels, suggesting impairments in oxidative defense. Here we performed unbiased, unsupervised and integrated multi-'omic analysis of metabolomic and transcriptomic datasets from mice flown aboard the Space Shuttle Atlantis. Enrichment analyses of metabolite and gene sets showed significant changes in osmolyte concentrations and pathways related to glycerophospholipid and sphingolipid metabolism, likely consequences of relative dehydration of the spaceflight mice. However, we also found increased enrichment of aminoacyl-tRNA biosynthesis and purine metabolic pathways, concomitant with enrichment of genes associated with autophagy and the ubiquitin-proteasome. When taken together with a down-regulation in NRF2-mediated signaling, our analyses suggest that decreased hepatic oxidative defense may lead to aberrant tRNA post-translational processing, induction of degradation programs and senescence-associated mitochondrial dysfunction in response to the spaceflight environment..

Autophagy↗
NASA NTRS2018

Effect of Ex Vivo Ionizing Radiation on Static and Fatigue Properties of Mouse Vertebral Bodies

For a variety of medical and scientific reasons, human bones can be exposed to a wide range of ionizing radiation levels. In vivo radiation therapy (0.05 kGy) is used in cancer treatment, and ex vivo irradiation (25-35 kGy) is used to sterilize bone allografts. Ionizing radiation in these applications has been shown to increase risk of fracture, decrease bone quality and degrade collagen integrity. Past studies have investigated the deleterious effects of radiation on cortical or trabecular bone specimens individually, but to date no studies have examined whole bones containing both cortical and trabecular tissue. Furthermore, a clear relationship between the dose and the mechanical and biochemical response of bone's extracellular matrix has yet to be established for doses ranging from cancer therapy to allograft sterilization (0.05-35 kGy). To gain insight into these issues, we conducted an ex vivo radiation study to investigate non-cellular (i.e. matrix) effects of ionizing radiation dose on vertebral whole bone mechanical properties, over a range of radiation doses (0.05-35 kGy), with a focus on any radiation-induced changes in collagen. With underlying mechanisms of action in mind, we hypothesized that any induced reductions in mechanical properties would be associated with changes in collagen integrity. METHODS: 20-week old female mice were euthanized and the lumbar spine was dissected using IACUC approved protocols. The lumbar vertebrae (L1- S1) were extracted from the spine via cuts through adjacent intervertebral discs, and the endplates, posterior processes, surrounding musculature, and soft tissues were removed (approx. 1.5mm diameter, approx. 2mm height). Specimens were randomly assigned to one of five groups for ex vivo radiation exposure: x-ray irradiation at 0.05, 1, 17, or 35 kGy, or a 0 kGy control. Following irradiation, the vertebrae were imaged using microcomputed tomography (micro-CT) and then subjected to either monotonic compressive loading to failure or uniform cyclic compressive loading. During cyclic testing, samples were loaded in force control to a force level that corresponded to a strain of 0.46%, as determined in advance by a linearly elastic micro-CT-based finite element analysis for each specimen. Tests were stopped at imminent fracture, defined as a rapid increase in strain. The main outcome for the monotonic test was the strength (maximum force); for cyclic testing it was the fatigue life (log of the number of cycles of loading at imminent failure). A fluorometric assay was used on the S1 vertebrae to measure the number of non-enzymatic collagen crosslinks[4]. A one-way ANOVA was performed on mechanical properties and collagen crosslinks; means were compared with controls using Dunnett's method, with a Tukey-Kramer post-hoc analysis when significance was found (p < or = 0.05). RESULTS: Compared to the unirradiated control group, the concentration of non-enzymatic collagen crosslinks was significantly increased for all irradiated groups (p < 0.0001), and being higher by at least 50% (Figure 1a). By contrast, the radiation effects on the collagen were only evident at the higher doses. For irradiation exposures of 17 kGy or more, strength decreased substantially as the radiation level was increased, but no effect was evident below 17 kGy (Figure 1b). There was no significant change in the stiffness or maximum displacement for any radiation dose (p>0.05). The finite element analysis prescribed force level for cyclic loading exceeded the measured (monotonic) strength of the 17 and 35 kGy irradiated groups (mean +/- SD, 20.6 +/- 5.6 N; 13.2 +/- 3.7 N, respectively) and therefore these groups were eliminated from the fatigue study. The fatigue life for the 0.05 and 1 kGy groups were similar to each other and were not statistically significantly different from the control group (Figure 1c).

radiation↗
NASA NTRS2019

Overexpression of Catalase in Mitochondria Mitigates the Effects of Simulated Microgravity and Social Isolation on Cytokine Expression in Mouse Hippocampus

Space flight missions are becoming longer and more common and evidence points to the physiological toll the missions have on the human body. Aging, sedentary lifestyle, and spaceflight have similar degenerative effects on almost every part of our body; both exposure to the space environment and aging result in cardiovascular deconditioning, bone loss, muscle atrophy, brain changes, and immune response impairment. We hypothesize that exposure to the space environment generates excessive Reactive Oxygen Species (ROS), which results in neuroinflammation and aging-like degenerative symptoms in the brain. We used the hindlimb unloading (HU) model to mimic microgravity with either paired or single housed animals (social isolation). Responses to 30d (30 days) of HU were compared in wildtype or transgenic MCAT (Mitochondrial-targeted CATalase) mice, in which mitochondrial ROS is quenched by over-expression of human catalase. Expression of 4-Hydroxynonenal (4HNE) and Park7 (redox-sensitive chaperone and sensor of oxidative stress) were measured by ELISA (Enzyme-Linked ImmunoSorbent Assay), a protein array quantified from the hippocampal cytokines and 8-hydroxy-2'-deoxyguanosine in serum was measured by ELISA to assess oxidative DNA damage. Preliminary analysis of cage behavior patterns from video collected at the end of the study showed that MCAT HU mice (socially housed) were more active and conducted more exploratory activities compared to NL (Normally Loaded). Our biochemical results showed simulated microgravity and/or social isolation caused changes in levels of cytokines related to immune responses. Two-way ANOVA (Analysis of Variance) revealed significant interaction effects of HU and genotype in expression levels of five cytokines (out of 35) in socially-housed animals. Elevation of these generally pro-inflammatory cytokines by HU in WT (Wild Type) mice was mitigated in MCAT mice, suggesting a role for mitochondrial ROS signaling in inflammatory CNS (Central Nervous System) responses to microgravity. Interestingly, some of these cytokines in the hippocampus displayed strong correlations to the 4HNE levels. We also found substantive cytokine responses to social isolation in the hippocampus; housing and genotype interaction effects were significant (by 2-Factor ANOVA) for 15 cytokines, most of which were mitigated in MCAT mice.Taken together, our results showed that both simulated microgravity and social isolation influenced cytokine levels in the hippocampus and MCAT mice were at least partially protected from these changes. These findings implicate a potentially important role for mitochondrial ROS in CNS responses to the challenges posed by long duration spaceflight.

MCAT↗
NASA NTRSDate not supplied

Impact of Simulated Galactic Cosmic Radiation and Hindlimb Unloading on the Mouse Adrenal Gland Morphology and Histology

Stress related impact of Galactic Cosmic Radiation (GCR) combined with microgravity in space are concerns for astronauts going beyond the Van Allen belts on their way to the Moon and Mars. The adrenal gland is the central endocrine tissue involved in stress management, adrenal hormones regulate the immune system, cellular and tissue metabolism, and glucose and sodium balances. Adult (6 m old) female (n=18) and male (n=18) C57BL/6J mice were divided evenly into 6 treatment groups (control, hindlimb unloading (HU), irradiated (IR), HU+IR, group house control, and group house IR). Adrenals were dissected and fixed for 24 h in 4% paraformaldehyde, followed by transfer to 70% EtOH, and shipment to KUMC. Adrenals were then embedded in paraffin and serial sectioned and 4 central sections from each were stained with H&E, prior to imaging on a Nikon 80i microscope. Whole adrenal cross section area, medullary area, and cortex area were determined. General adrenal gland morphology and histology did not appear to be affected by hindlimb unloading or GCR exposure. Total cross-sectional area, medullary region, and cortex of the adrenal were not different across treatment groups. Male adrenal cross-sectional areas are half the size of the female adrenals, due to a difference in cortex area. In conclusion, simulated microgravity and GCR did not dramatically affect the adrenal gland histology or size. Support from Accelerate Cancer Education Internship Program (KUCC) and KINBRE Summer Scholars Program (KUMC) and NASA Human Research Program (HRP) Human Factors Behavioral Performance Element Grant 18 18FLAG 2 0028

radiation↗