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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 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Aristolochic acid-induced genotoxicity and toxicogenomic changes in rodents

Aristolochic acid (AA) is a group of structurally related nitrophenanthrene carboxylic acids found in many plants that are widely used by many cultures as traditional herbal medicines. AA is a causative agent for Chinese herbs nephropathy, a term replaced later by AA nephropathy. Evidence indicates that AA is nephrotoxic, genotoxic, and carcinogenic in humans; and it also induces tumors in the forestomach, kidney, renal pelvis, urinary bladder, and lung of rats and mice. Therefore, plants containing AA have been classified as carcinogenic to humans (Group 1) by the International Agency for Research on Cancer. In our laboratories, we have conducted a series of genotoxicity and toxicogenomic studies in the rats exposed to AA of 0.1–10 mg/kg for 12 weeks. Our results demonstrated that AA treatments induced DNA adducts and mutations in the kidney, liver, and spleen of rats, as well as significant alteration of gene expression in both its target and nontarget tissues. AA treatments altered mutagenesis- or carcinogenesis-related microRNA expression in rat kidney and resulted in significant changes in protein expression profiling. We also applied benchmark dose (BMD) modeling to the 3-month AA-induced genotoxicity data. The obtained BMDL10 (the lower 95% confidence interval of the BMD 10 that is a 10% increase over the background level) for AA-induced mutations in the kidney of rats was about 7 μg/kg body weight per day. This review constitutes an overview of our investigations on AA-induced genotoxicity and toxicogenomic changes including gene expression, microRNA expression, and proteomics; and presents updated information focused on AA-induced genotoxicity in rodents.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1988

Proceedings of a workshop on Lighting Requirements in Microgravity: Rodents and Nonhuman Primates

A workshop, sponsored by Ames Research Center, was held at San Jose State University, San Jose, California, July 16-17, 1987, to discuss and correlate observations and theories relating to lighting requirements in animal habitats for rodents and nonhuman primates in microgravity (near space). This volume represents the results of the workshop. It contains a summary of the conclusions reached and recommendations for lighting animal housing modules used in microgravity related projects. The recommendations cover various aspects of habitat lighting including engineering standards for intensity, spectral properties, and light cycle controls.

Holley, Daniel C.↗
NASA NTRS1994

Experiment K-7-29: Connective Tissue Studies: Rodent Tissue Repair: Skeletal Muscle - Part 3

Myofiber injury-repair was studied in the rat gastrocnemius following a crush injury to the lower leg prior to flight in order to understand if the regenerative responses of muscles are altered by the lack of gravitational forces during Cosmos 2044 flight. After 14 days of flight, the gastrocnemius muscle was removed from the 5 injured flight rodents and various Earth-based treatment groups for comparison. The Earth-based animals consisted of three groups of five rats with injured muscles from a simulated, tail-suspended, and vivarium as well as an uninjured basal group. The gastrocnemius muscle from each was evaluated by histochemical and immunohistochemical techniques to document myofiber, vascular, and connective tissue alterations following injury. In general the repair process was somewhat similar in all injured muscle samples with regard to extracellular matrix organization and myofiber regeneration. Small and large myofibers were present with a newly organized extracellular matrix indicative of myogenesis and muscle regeneration. In the tail-suspended animals, a more complete repair was observed with no enlarged area of non-muscle cells or matrix material visible. In contrast, the muscle samples from the flight animals were less well differentiated with more macrophages and blood vessels in the repair region but small myofibers and proteoglycans, nevertheless, were in their usual configuration. Thus, myofiber repair did vary in muscles from the different groups, but for the most part, resulted in functional muscle tissue.

Stauber, W.↗
NASA NTRS1980

The Manufacture, Shipping and Receiving and Quality Control of Rodent Bedding Materials

The criteria for rodent bedding and nesting materials are discussed. The literature is reviewed regarding sources of bedding materials, manufacturing methods, quality control, procedures (microbiological, physical and chemical), storage, methods, shipment, methods of use and disposal, current knowledge concerning bedding effects on animals as related to research and testing and legal aspects. Future needs, especially with respect to the promulgation of standards, also are addressed.

Kraft, Lisbeth M.↗
NASA NTRS2001

The Effects of Long-Term Feeding of Rodent Food Bars on Lipid Peroxidation And Antioxidant Enzyme Levels In Fisher Rats

A specialized rodent food bar diet has been developed and utilized successfully for short-duration shuttle missions. Recent tests conducted in preparation for experiments aboard the International Space Station (ISS) indicated that long-term food bar feeding for three months induced hyperlipidemia in rats. This study examined oxidative stress status in livers of these same animals. Spectrophotometric analysis of 79 Fischer rat livers (40 female and 39 male) for lipid peroxidation (LPO) and superoxide dismutase (SOD) was conducted using Bioxytech LPO-587(TM) assay kit and SOD-525(Tm) assay kit, respectively. The treatment groups consisted of 20 male CHOW and 19 male FOOD BAR rats and 20 female CHOW and 20 female FOOD BAR rats. Statistical analysis to compare differences between groups was performed by standard analysis of variance procedures. The male FOOD BAR group LPO mean (3.6 +/- 0.2 mmol/g) was significantly (p less than or equal to 0.05) greater than that of the male CHOW group (2.1 +/-0.1 mmol/g). Moreover the female FOOD BAR group LPO mean (2.9 +/-0.1 mmol/g) was also significantly greater than the female CHOW group mean (2.2 +/-0.1 mmol/g). The mean values for SOD in both male and female groups showed no significant differences between CHOW and FOOD BAR groups. These results show that LPO levels were significantly higher in both the male and female FOOD BAR groups compared to CHOW groups and that there was no concomitant increase in SOD levels across the group. In addition, males showed a greater difference than females in terms of LPO levels. These findings suggest a need for further investigation into the use of the current food bar formulation for long-term experiments such as those planned for the ISS.

Ramirez, Joel↗
NASA NTRS2001

NASA Rodent Foodbar: Long Term Effects in Swiss Webster Mice

Swiss Webster male and female mice (150 of each) were fed NASA Rodent Foodbar for more than 110 days to test the diet's nutritional adequacy for use in future long-term studies aboard the International Space Station. Mice were grouped three to a cage (one cage = one sample) and cages were assigned to either Foodbar or Purina Chow #5001 (control) diet groups. Body weights, food intake, and water intake were obtained throughout the study. There were no significant differences in body weights between male Foodbar fed and Chow fed males (p=0.58), and at 15 weeks into the female mouse study there appear to be no significant body weight differences. Both male and female Foodbar fed groups consumed more food and less water than their Chow controls, both factors thought to be attributable to the high moisture content of the Foodbars (26% versus 10% for Chow). All differences in gross food and water consumption had p-values of less than 0.01. When food and water intake were adjusted for the moisture content in the food, both male and female Foodbar fed animals consumed less food, but still had a lower water intake rate than their controls. (p is less than 0.01). Preliminary analysis on blood samples from male and female halfway point dissections suggests differences in glucose and fat metabolism. In both male and female Foodbar fed animals, blood glucose values were significantly lower (p is less than 0.01) but there were no significant differences in cholesterol levels (p=0.51). In Foodbar fed females, triglycerides were significantly higher (p is less than 0.01). These data suggest that Foodbars allow for normal growth in Swiss Webster mice, but affect some blood chemistry parameters.

Santiago, D. L.↗
NASA NTRS2002

Body Composition of Rats on NASA Rodent Foodbar Versus Purina Lab Chow

The objective of this study is to test the nutritional adequacy of the NASA Rodent Foodbar for long term use for rats. The Foodbar was tested on two rat strains, Sprague Dawley and Fischer 344. Rats were fed either Foodbar or the control diet, Purina Chow #5012. Body composition analysis was performed on a selected number of samples (n=6 for each gender and treatment group) as part of extensive testing of the Foodbar. Water, fat, ash, and protein (and their percentages) for both treatment groups were compared. Sprague Dawley Foodbar fed rats had a lower % protein than Chow fed rats (25.8% vs. 30.0%). In addition, Sprague Dawley females fed Foodbar had higher total fat (42.1g vs. 24.6g) and % fat (16.4% vs. 10.5%), but lower % water (51.3% vs. 54.8%) than Sprague Dawley females fed Chow. Fischer 344 Foodbar fed rats had a lower % water (47.4% vs. 49,3%) and total water (93.2g vs. 99.6g). In addition, Fischer 344 Foodbar males had higher % fat (17.0% vs. 13.8%) and total fat (43.0g vs. 34.7g). The data suggests that body composition of Foodbar fed rats tends to have lower water content but a higher fat content compared to controls, but not all results are the same for different strains and even different genders within the same strains. The data obtained here, in addition to other data, helps provide a better understanding of the nutritional adequacy of the Foodbar and whether the formula may need to be modified.

Yu, Diane Sau Mun↗
NASA NTRS2002

Hypergravity Effects on Rodent Pregnancy and Parturition

No mammal has yet undergone birth, or parturition, in the microgravity of space. Previous studies (Ronco & Alberts, 2000) have shown that mid-pregnant rat dams exposed to spaceflight (0-g) and landed 48-72 hrs before term successfully delivered robust, healthy offspring Microgravity-exposed dams exhibited twice the expected numbers of labor contractions whereas length of pregnancy, duration of labor, fetal wastage, number of neonates born and litter gender ratios were identical to controls. In the present study, we report the results of rodent pregnancy and parturition at the opposite end of the gravity spectrum, in hypergravity. Dams exposed to either: 1.0-g, 1.5-g, 1.75-g or 2.0-g from Gestational day (G) 11 and throughout the births of their litters had comparable pregnancy and labor durations, fetal wastage, numbers of neonates born and litter Tender ratios. During parturition, hypergravity-exposed dams exhibited significantly fewer labor contractions as compared to 1.0-g controls. Dams that underwent birth in hypergravity had significantly fewer offspring surviving the immediate postpartum period (P1: 1.0-g, 11.92 +/- 2.84; 1.5-g, 10.88 +/- 2.17; 1.75-g, 9.22 +/-1.99; 2.0-g, 8.83 +/- 3.31). Within 24 hrs postpartum, neonatal survival was further diminished in hypergravity [P2: 100% (1.0-g); 96% (1.5-g); 96% (1.75-g); 73% (2.0-g)] and continued to decline (P10: 100%(1.0-g.); 90%(1.5-g); 87%(1.75-g), 40%(2.0-g)]. Neonatal losses stabilized by P5 for the 1.5-g andl.75-g conditions but continued until P9 for the 2.0-g condition. Together, these findings show that postnatal, but not prenatal, survival is compromised following birth in hypergravity, Maternal and neonatal factors that contribute to peri-parturitional vulnerability to altered gravity environments will be discussed.

Ronca, A. E.↗
NASA NTRS2002

Hindlimb unloading rodent model: technical aspects

Since its inception at the National Aeronautics and Space Administration (NASA) Ames Research Center in the mid-1970s, many laboratories around the world have used the rat hindlimb unloading model to simulate weightlessness and to study various aspects of musculoskeletal loading. In this model, the hindlimbs of rodents are elevated to produce a 30 degrees head-down tilt, which results in a cephalad fluid shift and avoids weightbearing by the hindquarters. Although several reviews have described scientific results obtained with this model, this is the first review to focus on the technical aspects of hindlimb unloading. This review includes a history of the technique, a brief comparison with spaceflight data, technical details, extension of the model to mice, and other important technical considerations (e.g., housing, room temperature, unloading angle, the potential need for multiple control groups, age, body weight, the use of the forelimb tissues as internal controls, and when to remove animals from experiments). This paper is intended as a reference for researchers, reviewers of manuscripts, and institutional animal care and use committees. Over 800 references, related to the hindlimb unloading model, can be accessed via the electronic version of this article.

NASA Discipline Musculoskeletal↗
NASA NTRS1996

Effects of altered loading states on muscle plasticity: what have we learned from rodents?

This paper summarizes the key findings concerning the adaptive properties of rodent muscle in response to altered loading states. When the mechanical stress on the muscle is chronically increased, the muscle adapts by hypertrophying its fibers. This response is regulated by processes resulting in contractile protein expression reflecting slower phenotypes, thereby enabling the muscle to better support load-hearing activity. In contrast, reducing the load-bearing activity induces an opposite response whereby muscles used for both antigravity function and locomotion atrophy while transforming some of the slow fibers into faster contractile phenotypes. Accompanying the atrophy is both a reduced power generating and activity sustaining capability. These adaptive processes are regulated by both transcriptional and translational processes. Available evidence further suggests that the interaction of heavy resistance activity and hormonal/growth factors (insulin-like growth factor, growth hormone, glucocorticoids, etc.) are critical in the maintenance of muscle mass and function. Also resistance training, in contrast to other activities such as endurance running, provides a more economical form of stress because less mechanical activity is required to maintain muscle homeostasis in the context of chronic states of weightlessness.

Non-NASA Center↗
NASA NTRS1993

Substrate oxidation capacity in rodent skeletal muscle: effects of exposure to zero gravity

A study was conducted, as part of the integrated National Aeronautics and Space Administration Space Life Sciences 1 mission flown in June of 1991, to ascertain the effects of 9 days of exposure to zero gravity on the capacity of rodent skeletal muscle fiber types to oxidize either [14C]pyruvate or [14C]palmitate under state 3 metabolic conditions, i.e., nonlimiting amounts of substrate and cofactors. In addition, activity levels of marker enzymes of the tricarboxylic acid cycle, malate shuttle, and beta-oxidation were measured. Results showed that significant differences in muscle weight occurred in both the predominantly slow vastus intermedius and predominantly fast vastus lateralis of flight vs. control groups (P < 0.05). Total protein content of the muscle samples was similar between groups. Both pyruvate oxidation capacity and the marker oxidative enzymes were not altered in the flight relative to control animals. However, the capacity to oxidize long-chain fatty acids was significantly reduced by 37% in both the high- and low-oxidative regions of the vastus muscle (P < 0.05). Although these findings of a selective reduction in fatty acid oxidation capacity in response to spaceflight are surprising, they are consistent with previous findings showing 1) an increased capacity to take up glucose and upregulate glucose transporter proteins and 2) a marked accumulation of triglycerides in the skeletal muscles of rats subjected to states of unloading. Thus, skeletal muscle of animals exposed to non-weight-bearing environments undergo subcellular transformations that may preferentially bias energy utilization to carbohydrates.

NASA Discipline Musculoskeletal↗
NASA NTRS2005

Effects of space flight conditions on the function of the immune system and catecholamine production simulated in a rodent model of hindlimb unloading

The rodent model of hindlimb unloading has been successfully used to simulate some of the effects of space flight conditions. Previous studies have indicated that mice exposed to hindlimb-unloading conditions have decreased resistance to infections compared to restrained and normally housed control mice. OBJECTIVE: The purpose of this study was to clarify the mechanisms involved in resistance to infection in this model by examining the effects of hindlimb unloading on the function of the immune system and its impact on the production of catecholamines. METHODS: Female Swiss Webster mice were hindlimb-unloaded during 48 h and the function of the immune system was assessed in spleen and peritoneal cells immediately after this period. In addition, the kinetics of catecholamine production was measured throughout the hindlimb-unloading period. RESULTS: The function of the immune system was significantly suppressed in the hindlimb-unloaded group compared to restrained and normally housed control mice. Levels of catecholamines were increased in the hindlimb-unloaded group and peaked at 12 h following the commencement of unloading. CONCLUSION: These results suggest that physiological responses of mice are altered early after hindlimb unloading and that catecholamines may play a critical role in the modulation of the immune system. These changes may affect the ability of mice to resist infections. Copyright (c) 2005 S. Karger AG, Basel.

NASA Discipline Regulatory Physiology↗
NASA NTRS2012

Pulmonary Toxicity Studies of Lunar Dust in Rodents

NASA has been contemplating returning astronauts to the moon for long-duration habitation and research and using it as a stepping-stone to Mars. Other spacefaring nations are planning to send humans to the moon for the first time. The surface of the moon is covered by a layer of fine dust. Fine terrestrial dusts, if inhaled, are known to pose a health risk to humans. Some Apollo crews briefly exposed to moon dust that adhered to spacesuits and became airborne in the Lunar Module reported eye and throat irritation. The habitable area of any lunar landing vehicle or outpost would inevitably become contaminated with lunar dust. To assess the health risks of exposure of humans to airborne lunar dust, we evaluated the toxicity of Apollo 14 moon dust in animal lungs. Studies of the pulmonary toxicity of a dust are generally first done by intratracheal instillation (ITI) of aqueous suspensions of the test dust into the lungs of rodents. If a test dust is irritating or cytotoxic to the lungs, the alveolar macrophages, after phagocytizing the dust particles, will release cellular messengers to recruit white blood cells (WBCs) and to induce dilation of blood capillary walls to make them porous, allowing the WBCs to gain access to the alveolar space. The dilation of capillary walls also allows serum proteins and water entering the lung. Besides altering capillary integrity, a toxic dust can also directly kill the cells that come into contact with it or ingest it, after which the dead cells would release their contents, including lactate dehydrogenase (a common enzyme marker of cell death or tissue damage). In the treated animals, we lavaged the lungs 1 and 4 weeks after the dust instillation and measured the concentrations of these biomarkers of toxicity in the bronchioalveolar lavage fluids to determine the toxicity of the dust. To assess whether the inflammation and cellular injury observed in the biomarker study would lead to persistent or progressive histopathological changes, a similar study was conducted to microscopically examine rat lung tissue and the associated lymph nodes for lesions, including fibrosis, 1 or 3 months after the instillation. The results from this ITI study led us to select two concentrations (20 and 60 mg/cu m) for an inhalation study, in which rats were exposed to lunar dust 6 h daily for 4 weeks (5d/wk). Similar biochemical and histopathological assessments were carried out in these rats 1 day or 1, 4, or 13 weeks after the dust exposure. Rats exposed to lunar dust by ITI or inhalation showed effects indicating that the dust is moderately toxic. The data will be useful to establish safe exposure limits for astronauts working in a lunar habitat and also help engineers designing dust mitigation systems for lunar vehicles and habitats.

Lam, Chiu-Wing↗
NASA NTRS2014

Ames Life Science Data Archive: Translational Rodent Research at Ames

The Life Science Data Archive (LSDA) office at Ames is responsible for collecting, curating, distributing and maintaining information pertaining to animal and plant experiments conducted in low earth orbit aboard various space vehicles from 1965 to present. The LSDA will soon be archiving data and tissues samples collected on the next generation of commercial vehicles; e.g., SpaceX & Cygnus Commercial Cargo Craft. To date over 375 rodent flight experiments with translational application have been archived by the Ames LSDA office. This knowledge base of fundamental research can be used to understand mechanisms that affect higher organisms in microgravity and help define additional research whose results could lead the way to closing gaps identified by the Human Research Program (HRP). This poster will highlight Ames contribution to the existing knowledge base and how the LSDA can be a resource to help answer the questions surrounding human health in long duration space exploration. In addition, it will illustrate how this body of knowledge was utilized to further our understanding of how space flight affects the human system and the ability to develop countermeasures that negate the deleterious effects of space flight. The Ames Life Sciences Data Archive (ALSDA) includes current descriptions of over 700 experiments conducted aboard the Shuttle, International Space Station (ISS), NASA/MIR, Bion/Cosmos, Gemini, Biosatellites, Apollo, Skylab, Russian Foton, and ground bed rest studies. Research areas cover Behavior and Performance, Bone and Calcium Physiology, Cardiovascular Physiology, Cell and Molecular Biology, Chronobiology, Developmental Biology, Endocrinology, Environmental Monitoring, Gastrointestinal Physiology, Hematology, Immunology, Life Support System, Metabolism and Nutrition, Microbiology, Muscle Physiology, Neurophysiology, Pharmacology, Plant Biology, Pulmonary Physiology, Radiation Biology, Renal, Fluid and Electrolyte Physiology, and Toxicology. These experiment descriptions and data can be accessed online via the public LSDA website (http://lsda.jsc.nasa.gov) and information can be requested via the Data Request form at http://lsda.jsc.nasa.gov/common/dataRequest/dataRequest.aspx or by contacting the ALSDA Office at: Alison.J.French@nasa.gov

Life Sciences↗
NASA NTRS2017

Network Analysis of Rodent Transcriptomes in Spaceflight

Network analysis methods leverage prior knowledge of cellular systems and the statistical and conceptual relationships between analyte measurements to determine gene connectivity. Correlation and conditional metrics are used to infer a network topology and provide a systems-level context for cellular responses. Integration across multiple experimental conditions and omics domains can reveal the regulatory mechanisms that underlie gene expression. GeneLab has assembled rich multi-omic (transcriptomics, proteomics, epigenomics, and epitranscriptomics) datasets for multiple murine tissues from the Rodent Research 1 (RR-1) experiment. RR-1 assesses the impact of 37 days of spaceflight on gene expression across a variety of tissue types, such as adrenal glands, quadriceps, gastrocnemius, tibalius anterior, extensor digitorum longus, soleus, eye, and kidney. Network analysis is particularly useful for RR-1 -omics datasets because it reinforces subtle relationships that may be overlooked in isolated analyses and subdues confounding factors. Our objective is to use network analysis to determine potential target nodes for therapeutic intervention and identify similarities with existing disease models. Multiple network algorithms are used for a higher confidence consensus.

genomics↗