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Rodent Research-1 Validation of Rodent Hardware
To achieve novel science objectives, validation of a rodent habitat on ISS will enable - In-flight analyses during long duration spaceflight- Use of genetically altered animals- Application of modern analytical techniques (e.g. genomics, proteomics, and metabolomics)
New Development in NASA's Rodent Research Hardware for Conducting Long Duration Biomedical and Basic Research in Space
Animal models, particularly rodents, are the foundation of pre-clinical research to understand human diseases and evaluate new therapeutics, and play a key role in advancing biomedical discoveries both on Earth and in space. The National Research Councils Decadal survey emphasized the importance of expanding NASAs life sciences research to perform long duration, rodent experiments on the International Space Station (ISS). To accomplish this objective, flight hardware, operations, and science capabilities were developed at NASA Ames Research Center (ARC) to enhance science return for both commercial (CASIS) and government-sponsored rodent research. The Rodent Research program at NASA ARC has pioneered a new research capability on the International Space Station and has progressed toward translating research to the ISS utilizing commercial rockets, collaborating with academia and science industry, while training crewmembers to assist in performing research on orbit. Throughout phases of these missions, our practices, hardware and operations have evolved from tested to developed standards, and we are able to modify and customize our procedure and operations for mission specific requirements. The Rodent Research Habitat is capable of providing a living environment for animals on ISS according to standard animal welfare requirements. Using the cameras in the Habitat, the Rodent Research team has the ability to perform daily health checks on animals, and further analyze the collected videos for behavioral studies. A recent development of the Rodent Research hardware is inclusion of enrichment, to provide the animals the ability to rest and huddle. The Enrichment Hut is designed carefully for adult mice (up to 35 week old) within animal welfare, engineering, and operations constraints. The Hut is made out of the same stainless steel mesh as the cage interior, it has an ingress and an egress to allow animals move freely, and a hinge door to allow crewmembers remove the animals easily. The Rodent Research team has also developed Live Animal Return (LAR) capability, which will be implemented during Rodent Research-5 mission for the first time. The animals will be transported from the Habitat to a Transporter, which will return on the Dragon capsule and splashes down in the Pacific Ocean. Once SpaceX retrieves the Dragon, all powered payloads will be transferred to a SeaVan and transferred to the Long Beach pier. The NASA team then receives the transporter and delivers to a PI-designated laboratory within 120 mile radius of Long Beach. This is a significant improvement allowing researchers to examine animals within 72 hrs. of reentry or to conduct recovery experiments. Together, the hardware improvements and experience that the Rodent Research team has gained working with principal investigators and ISS crew to conduct complex experiments on orbit are expanding capabilities for long duration rodent research on the ISS to achieve both basic science and biomedical objectives.
Rodent Habitat on ISS: Advances in Capability for Determining Spaceflight Effects on Mammalian Physiology
Rodent research is a valuable essential tool for advancing biomedical discoveries in life sciences on Earth and in space. The National Research Counsel's Decadal survey (1) emphasized the importance of expanding NASAs life sciences research to perform long duration, rodent experiments on the International Space Station (ISS). To accomplish this objective, new flight hardware, operations, and science capabilities were developed at NASA ARC to support commercial and government-sponsored research. The flight phases of two separate spaceflight missions (Rodent Research-1 and Rodent Research-2) have been completed and new capabilities are in development. The first flight experiments carrying 20 mice were launched on Sept 21, 2014 in an unmanned Dragon Capsule, SpaceX4; Rodent Research-1 was dedicated to achieving both NASA validation and CASIS science objectives, while Rodent Reesearch-2 extended the period on orbit to 60 days. Groundbased control groups (housed in flight hardware or standard cages) were maintained in environmental chambers at Kennedy Space Center. Crewmembers previously trained in animal handling transferred mice from the Transporter into Habitats under simultaneous veterinary supervision by video streaming and were deemed healthy. Health and behavior of all mice on the ISS was monitored by video feed on a daily basis, and post-flight quantitative analyses of behavior were performed. The 10 mice from RR-1 Validation (16wk old, female C57Bl6/J) ambulated freely and actively throughout the Habitat, relying heavily on their forelimbs for locomotion. The first on-orbit dissections of mice were performed successfully, and high quality RNA (RIN values>9) and liver enzyme activities were obtained, validating the quality of sample recovery. Post-flight sample analysis revealed that body weights of FLT animals did not differ from ground controls (GC) housed in the same hardware, or vivarium controls (VIV) housed in standard cages. Organ weights analyzed post-flight showed that there were no differences between FLT and GC groups in adrenal gland and spleen weights, whereas FLT thymus and liver weights exceeded those of GC. Minimal differences between the control groups (GC and VIV) were observed. In addition, Over 3,000 aliquots collected post-flight from the four groups of mice were deposited into the Ames Life Science Data Archives for the Biospecimen Sharing Program and Genelab project. New capabilities recently developed include DEXA scanning, grip strength tests and male mice. In conclusion, new capability for long duration rodent habitation of group-housed rodents was developed and includes in-flight sample collection, thus avoiding the complication of reentry. Results obtained to date reveal the possibility of striking differences between the effects of short duration vs. long duration spaceflight. This Rodent Research system enables achievement of both basic science and translational research objectives to advance human exploration of space.
Advances in Rodent Research Missions on the International Space Station
A Research platform for rodent experiment on the ISS is an essential tool for advancing biomedical research in space. The Rodent Research allows for experiments of much longer duration that experiments on the Shuttle. NASA’s Rodent Research (RR)-1 mission was successfully completed, including post-flight analysis and achieved a number of objectives including validation of flight hardware, on-orbit operations, and science capabilities that were developed at the NASA Ames Research Center. Briefly, twenty C57BL/6J adult female mice were launched on the SpX4 Dragon vehicle, which thrived for up to 37 days in microgravity. Daily health checks of the mice were performed during the mission via downlinked video; all animals were healthy and displayed normal behavior without any significant signs of stress. Behavioral analysis demonstrated that Flight and Ground Control mice exhibited the same range of behaviors, including eating, drinking, exploratory behavior, self- and allo-grooming, and social interactions indicative of healthy animals. The animals were euthanized and select tissues were collected from some of the mice on orbit to assess the long-term sample storage capabilities of the ISS. The data obtained from the flight mice were comparable to those from the 3 groups of control mice (baseline, vivarium and ground controls), suggesting that the ISS has adequate capability to support long-duration rodent experimentations. We recovered over 35 tissues from 40 RR1 frozen carcasses, yielded over 3200 aliquots of tissues, and distributed to the scientific community, including NASA’s GeneLab and scientists in the U.S. through Biospecimen Sharing Program via Ames Life Science Data Archive. Tissues were also distributed to Russian research colleagues at the Institute for Biomedical Problems. The expression levels of select genes including albumin, catalase, GAPDH, HMGCoA Reductase, and IGF1 were determined using RNA isolated from the livers by qPCR and no significant differences by one factor ANOVA were found between flight and ground control groups. In addition, some of the liver samples were subject to transcriptomics, epigenomics and proteomics. The data are now available to the scientific community through GeneLab’s open science data website. Since the RR1 mission, another long duration mission (Rodent Research-2) was completed on the ISS in 2015 in which 20 female C57 BL/6J mice were successfully maintained on the ISS for varying time points, with the last group of 5 animals being on-orbit for 54 days. This second Rodent Research flight expanded the program’s capabilities with the introduction of new technologies including blood collection and separation and bone densitometry scanning. Furthermore, we have continued to expand the ISS’s capabilities by running a series of ground-based verification testing using male mice. Our next step is to fly male mice for Rodent Research-4 on SpaceX-10 to study the effects of microgravity on bone healing and regeneration. It will be the first long-duration mission using male mice using Rodent Hardware. In addition, the number of mice will increase from 20 mice (on RR-1 and RR-2) to 40 for RR-4. When samples return to Earth, a number of tissues will be dissected from the frozen carcasses and select tissue samples will become available to the scientific community via BSP. Altogether, we have continued to expand our capabilities for performing long-duration missions on the ISS as emphasized in the National Research Council’s Decadal Survey released in 2011 and to maximize science return from each mission.
Rodent Research on the International Space Station - A Look Forward
Rodent Research on the International Space Station (ISS) is one of the highest priority science activities being supported by NASA and is planned for up to two flights per year. The first Rodent Research flight, Rodent Research-1 (RR-1) validates the hardware and basic science operations (dissections and tissue preservation). Subsequent flights will add new capabilities to support rodent research on the ISS. RR-1 will validate the following capabilities: animal husbandry for up to 30 days, video downlink to support animal health checks and scientific analysis, on-orbit dissections, sample preservation in RNA. Later and formalin, sample transfer from formalin to ethanol (hindlimbs), rapid cool-down and subsequent freezing at -80 of tissues and carcasses, sample return and recovery. RR-2, scheduled for SpX-6 (Winter 20142015) will add the following capabilities: animal husbandry for up to 60 days, RFID chip reader for individual animal identification, water refill and food replenishment, anesthesia and recovery, bone densitometry, blood collection (via cardiac puncture), blood separation via centrifugation, soft tissue fixation in formalin with transfer to ethanol, and delivery of injectable drugs that require frozen storage prior to use. Additional capabilities are also planned for future flights and these include but are not limited to male mice, live animal return, and the development of experiment unique equipment to support science requirements for principal investigators that are selected for flight. In addition to the hardware capabilities to support rodent research the Crew Office has implemented a training program in generic rodent skills for all USOS crew members during their pre-assignment training rotation. This class includes training in general animal handling, euthanasia, injections, and dissections. The dissection portion of this training focuses on the dissection of the spleen, liver, kidney with adrenals, brain, eyes, and hindlimbs. By achieving and maintaining proficiency in these basic skills as part of the nominal astronaut training curriculum this allows the rodent research program to focus the mission specific crew training on scientific requirements of research and operations flow.
Semi-Autonomous Rodent Habitat for Deep Space Exploration
NASA has flown animals to space as part of trailblazing missions and to understand the biological responses to spaceflight. Mice traveled in the Lunar Module with the Apollo 17 astronauts and now mice are frequent research subjects in LEO on the ISS. The ISS rodent missions have focused on unravelling biological mechanisms, better understanding risks to astronaut health, and testing candidate countermeasures. A critical barrier for longer-duration animal missions is the need for humans-in-the-loop to perform animal husbandry and perform routine tasks during a mission. Using autonomous or telerobotic systems to alleviate some of these tasks would enable longer-duration missions to be performed at the Deep Space Gateway. Rodent missions performed using the Gateway as a platform could address a number of critical risks identified by the Human Research Program (HRP), as well as Space Biology Program questions identified by NRC Decadal Survey on Biological and Physical Sciences in Space, (2011). HRP risk areas of potentially greatest relevance that the Gateway rodent missions can address include those related to visual impairment (VIIP) and radiation risks to central nervous system, cardiovascular disease, as well as countermeasure testing. Space Biology focus areas addressed by the Gateway rodent missions include mechanisms and combinatorial effects of microgravity and radiation. The objectives of the work proposed here are to 1) develop capability for semi-autonomous rodent research in cis-lunar orbit, 2) conduct key experiments for testing countermeasures against low gravity and space radiation. The hardware and operations system developed will enable experiments at least one month in duration, which potentially could be extended to one year in duration. To gain novel insights into the health risks to crew of deep space travel (i.e., exposure to space radiation), results obtained from Gateway flight rodents can be compared to ground control groups and separate groups of mice exposed to simulated Galactic Cosmic Radiation (at the NASA Space Radiation Lab). Results can then be compared to identical experiments conducted on the ISS. Together results from Gateway, ground-based, and ISS rodent experiments will provide novel insight into the effects of space radiation.
Signaling from below: rodents select for deeper fruiting truffles with stronger volatile emissions
Many plant and fungal species use volatile organic compounds (VOCs) as chemical signals to convey information about the location or quality of their fruits or fruiting bodies to animal dispersers. Identifying the environmental factors and biotic interactions that shape fruit selection by animals is key to understanding the evolutionary processes that underpin chemical signaling. Using four Elaphomyces truffle species, we explored the role of fruiting depth, VOC emissions, and protein content in selection by five rodent species. We used stable isotope analysis of nitrogen (δ15N) in truffles to estimate fruiting depth, proton-transfer-reaction mass spectrometry to determine volatile emission composition, and nitrogen concentrations to calculate digestible protein of truffles. We coupled field surveys of truffle availability with truffle spore loads in rodent scat to determine selection by rodents. Despite presumably easier access to the shallow fruiting species, E. americanus (0.5-cm depth) and E. verruculosus (2.5-cm depth), most rodents selected for truffles fruiting deeper in the soil, E. macrosporus (4.1-cm depth) and E. bartlettii (5.0-cm depth). The deeper fruiting species had distinct VOC profiles and produced significantly higher quantities of odiferous compounds. Myodes gapperi (southern red-backed vole), a fungal specialist, also selected for truffles with high levels of digestible protein, E. verruculosus and E. macrosporus. Our results highlight the importance of chemical signals in truffle selection by rodents and suggest that VOCs are under strong selective pressures relative to protein rewards. Strong chemical signals likely allow detection of truffles deep within the soil and reduce foraging effort by rodents. Finally, for rodents that depend on fungi as a major food source, protein content may also be important in selecting truffles.
New Developments in NASA's Rodent Research Hardware for Conducting Long Duration Biomedical and Basic Research in Space
Animal models, particularly rodents, are the foundation of pre-clinical research to understand human diseases and evaluate new therapeutics, and play a key role in advancing biomedical discoveries both on Earth and in space. The National Research Councils Decadal survey emphasized the importance of expanding NASA's life sciences research to perform long duration, rodent experiments on the International Space Station (ISS) to study effects of the space environment on the musculoskeletal and neurological systems of mice as model organisms of human health and disease, particularly in areas of muscle atrophy, bone loss, and fracture healing. To accomplish this objective, flight hardware, operations, and science capabilities were developed at NASA Ames Research Center (ARC) to enhance science return for both commercial (CASIS) and government-sponsored rodent research. The Rodent Research Project at NASA ARC has pioneered a new research capability on the International Space Station and has progressed toward translating research to the ISS utilizing commercial rockets, collaborating with academia and science industry, while training crewmembers to assist in performing research on orbit. The Rodent Research Habitat provides a living environment for animals on ISS according to standard animal welfare requirements, and daily health checks can be performed using the habitats camera system. Results from these studies contribute to the science community via both the primary investigation and banked samples that are shared in publicly available data repository such as GeneLab. Following each flight, through the Biospecimen Sharing Program (BSP), numerous tissues and thousands of samples will be harvested, and distributed from the Space Life and Physical Sciences (SLPS) to Principal Investigators (PIs) through the Ames Life Science Data Archive (ALSDA). Every completed mission sets a foundation to build and design greater complexity into future research and answer questions about common human diseases. Together, the hardware improvements (enrichment, telemetry sensors, cameras), new capabilities (live animal return), and experience that the Rodent Research team has gained working with principal investigator teams and ISS crew to conduct complex experiments on orbit are expanding capabilities for long duration rodent research on the ISS to achieve both basic science and biomedical research objectives.
Maiden Voyage of the Rodent Habitat on ISS: Opportunities for Investigating Molecular Mechanisms and Biomedical Consequences of Long Duration Spaceflight
Research using rodents is an essential tool for advancing biomedical research on Earth and in space. The National Research Counsel’s Decadal survey (1) emphasized the importance of expanding NASAs life sciences research to perform long duration, rodent experiments on the International Space Station (ISS). To accomplish this objective, flight hardware, operations, and science capabilities were developed at NASA ARC to support both commercial and government-sponsored research. In preparation for the maiden voyage of the Rodent Habitat hardware and operations system (Rodent Research-1), and in close consultation with a Science Working Group comprised of veterinarians and experienced spaceflight investigators, we modified existing Animal Enclosure Module hardware, developed new hardware, operations, and science activities, and performed a series of ground-based verification tests. Preflight, ground based hardware tests included a simulation of SpaceX Dragon launch conditions (vibration and hypergravity) using the Transporter, and also two long-term biocompatibility tests (32 and 92 days) using the Habitat developed for long term housing on the ISS. The launch simulation test showed that adult mice housed in Transporter hardware adapted well, even if launch simulation was followed by a period of simulated weightlessness (via hind limb unloading). The biocompatibility tests demonstrated that the Habitat successfully supported animal health and also provided a useful video imaging system that enables frequent monitoring of animal health and behavior by veterinary and scientific experts on the ground, independent of ISS crew intervention. At the conclusion of all tests, mice were deemed healthy and suitable for conducting biological research. Additional preflight analyses of tissues preserved by freezing or fixation for gene expression analyses revealed that spleen and liver tissues recovered under conditions that simulated on-orbit activities yielded high quality RNA (RIN values 8-10) and liver enzyme activities and protein content (e.g. catalase). In addition, new methods were developed to optimize future science return by dissecting tissues post-euthanasia and storage. Various tissues were harvested from either intact or partially dissected, frozen carcasses after storage for ~2-6 months; most of the tissues (brain, heart, kidney, eye, adrenal glands and skeletal muscle) were of high RNA quality for science return, whereas some tissues (small intestine, bone marrow and bones) were not. These data demonstrated the protocols developed for future flight experiments supported science return despite delayed preservation post-euthanasia or prolonged storage, and furthermore, that high-quality RNA samples from many different tissues can be recovered by dissection following prolonged storage of the tissue in situ at -80˚C. The first flight experiments carrying 20 mice were launched on Sept 21, 2014 in an unmanned Dragon Capsule, SpaceX4; Rodent Research-1 is dedicated to achieving both NASA validation and CASIS science objectives. Ground based control groups (housed in flight hardware or standard cages) were maintained in environmental chambers at Kennedy Space Center. Crewmembers previously trained in animal handling transferred mice from the Transporter into Habitats under simultaneous veterinary supervision by video streaming and were deemed healthy. Health and behavior of all mice on the ISS was monitored by video feed on a daily basis. The 10 mice for validation (16wk old, female C57Bl6/J) ambulated freely and actively throughout the Habitat, relying heavily on their forelimbs for locomotion. The first on-orbit dissections of mice were performed successfully on Oct 12 and 13, 2014, and the validation mice will reside on ISS for up to 30 days. In conclusion, new capability for long duration rodent research is under development, including in-flight sample collection (which avoids the complication of reentry); results obtained to date will be described. This new Rodent Research system enables achievement of both basic science and translational research objectives to advance human exploration of space.
Nutritional Evaluation of NASA's Rodent Food Bar Diet
Tests are being conducted on NASA's rodent Food Bar in preparation for long-term use as the rat and mouse diet aboard the International Space Station. Nutritional analyses are performed after the bars are manufactured and then repeated periodically to determine nutritional stability. The primary factors analyzed are protein, ash, fat, fiber, moisture, amino acids, fatty acids, and minerals. Nutrient levels are compared to values published in the National Research Council's dietary requirements for rodents, and also to those contained in several commonly used commercial rodent lab diets. The Food Bar is manufactured from a powdered diet to which moisture is added as it is processed through an extruder. The bars are dipped into potassium sorbate, vacuum-sealed, and irradiated. In order to determine nutrient changes during extrusion and irradiation, the powdered diet, the non-irradiated bars, and the irradiated bars are all analyzed. We have observed lower values for some nutrients (iodine, vitamin K, and iron) in the Food Bars compared with NRC requirements. Many nutrients in the Food Bars are contained at a higher level than levels in the NRC requirements. An additional factor we are investigating is the 26% moisture level in the Food Bars, which drops to about 15% within a week, compared to a stable 10% moisture in many standard lab chow diets. In addition to the nutritional analyses, the food bar is being fed to several strains of rats and mice, and feeding study and necropsy results are being observed (Barrett et al, unpublished data). Information from the nutritional analyses and from the rodent studies will enable us to recommend the formulation that will most adequately meet the rodent Food Bar requirements for long-term use aboard the Space Station.
Evaluation of NASA Foodbars as a Standard Diet for Use in Short-Term Rodent Space Flight Studies
A standard rodent diet for space flight must meet the unique conditions imposed by the space environment and must be nutritionally adequate since diet can influence the outcome of experiments. This paper evaluates the use of National Aeronautics and Space Administration (NASA) developed Foodbars as a standard space flight diet for rats. The Foodbar's semi-purified formulation permits criteria such as nutrient consistency, high nutrient bioavailability and flexibility of formulation to be met. Extrusion of the semi-purified diet produces Foodbars with the proper texture and a non-crumbing solid form for use in space. Treatment of Foodbar with 0.1% potassium sorbate prevents mold growth. Irradiation (15-25 kGy) prevents bacterial growth and in combination with sorbate-treatment provides added protection against mold for shelf-stability. However, during the development process, nutrient analyses indicated that extrusion and irradiation produced nutrient losses. Nutrients were adjusted accordingly to compensate for processing losses. Nutrient analysis of Foodbars continues to be performed routinely to monitor nutrient levels. It is important that the standard rodent diet provide nutrients that will prevent deficiency but also avoid excess that may mask physiological changes produced by space flight. All vitamins levels in the Foodbars, except for vitamin K conformed to or exceeded the current NRC (1995) recommendations. All indispensable amino acids in Foodbar conformed to or exceeded the NRC nutrient recommendation for mice growth and rat maintenance. However, some indispensable amino acids were slightly below recommendations for rat reproduction/growth. Short-term (18-20 d) animal feeding studies indicated that Foodbars were palatable, supported growth and maintained health in rats. Results indicated that NASA rodent Foodbars meet both the physical and nutritional criteria required to support rodents in the space environment and thus, may be used successfully as a standard diet for short-term space flight studies. However, nutritional adequacy of NASA Rodent Foodbars as a standard diet on longer duration (>20 d) space flight missions remains to be determined.
Advances in Rodent Research Missions on the International Space Station
A research platform for rodent experiment on the ISS is a valuable tool for advancing biomedical research in space. Capabilities offered by the Rodent Research project developed at NASA Ames Research Center can support experiments of much longer duration on the ISS than previous experiments performed on the Space Shuttle. NASAs Rodent Research (RR)-1 mission was completed successfully and achieved a number of objectives, including validation of flight hardware, on-orbit operations, and science capabilities as well as support of a CASIS-sponsored experiment (Novartis) on muscle atrophy. Twenty C57BL6J adult female mice were launched on the Space-X (SpX) 4 Dragon vehicle, and thrived for up to 37 days in microgravity. Daily health checks of the mice were performed during the mission via downlinked video; all flight animals were healthy and displayed normal behavior, and higher levels of physical activity compared to ground controls. Behavioral analysis demonstrated that Flight and Ground Control mice exhibited the same range of behaviors, including eating, drinking, exploratory behavior, self- and allo-grooming, and social interactions indicative of healthy animals. The animals were euthanized on-orbit and select tissues were collected from some of the mice on orbit to assess the long-term sample storage capabilities of the ISS. In general, the data obtained from the flight mice were comparable to those from the three groups of control mice (baseline, vivarium and ground controls, which were housed in flight hardware), showing that the ISS has adequate capability to support long-duration rodent experiments. The team recovered 35 tissues from 40 RR-1 frozen carcasses, yielding 3300 aliquots of tissues to distribute to the scientific community in the U.S., including NASAs GeneLab project and scientists via Space Biology's Biospecimen Sharing Program Ames Life Science Data Archive. Tissues also were distributed to Russian research colleagues at the Institute for Biomedical Problems. The expression levels of select genes including albumin, catalase, GAPDH, HMGCoA Reductase, and IGF1 were determined using RNA isolated from the livers by qPCR and no significant differences by one factor ANOVA were found between flight and ground control groups. In addition, some of the liver samples were analyzed for transcriptomic, epigenomic and proteomic profiles; some of the data sets are now available to the scientific community through GeneLabs open science data website. A second long duration mission, Rodent Research-2 (RR-2) was completed on the ISS in 2015; 20 female C57BL6J mice were successfully maintained on the ISS for various durations, with the last group of 5 animals living on-orbit for 54 days. Furthermore, we continue to expand the ISSs capabilities by introducing new on-orbit technologies including blood collection and separation, bone densitometry scanning, muscle grip strength and anesthesia with recovery. In addition, series of ground-based verification testing to fly male mice and increase the total number of mice on-orbit from 20 to 40. Subsequent missions will provide the capability to return live mice from the ISS animals to evaluate recovery on Earth, further expanding operational and science capabilities of the RR project on the ISS.
Flying Through the Ages: Rodent Research for Human Health
As humans, we evolved, developed, grew, and now function in a continuous 1-gravity environment. Habitation in space poses unique challenges to human cells and organ systems. Biomedical research with rodents (primarily mice and rats) can help to both unravel molecular, cellular and physiologic mechanisms relevant to humans and test candidate interventions that mitigate adverse effects of space on humans, such as muscle atrophy, bone loss and cardiovascular deconditioning. One favored hypothesis that may explain the detrimental effects of spaceflight on humans is that reduced mechanical loading in microgravity accelerates aging. Rodents provide a relevant model system to study this problem as they age 40 times faster than humans. Now scientists from both public and commercial sectors conduct rodent experiments on the ISS using a new capability developed primarily at ARC. Results from the maiden voyage of the Rodent Research Project on the ISS reveal that long duration effects of spaceflight appear far different than short duration effects. Thus, Rodent Research missions on the ISS usher in a new era for exploration and biological discovery in space.
Water Shelf Life for Long-Duration Rodent Research Missions
The National Aeronautics and Space Administration Rodent Research Project habitat is a highly-specialized rodent husbandry caging system that enables mice to be flown to the International Space Station for a variety of bioscience studies in the unique microgravity and radiation environment. The habitat accommodates an internal water supply box containing four water access points and two one liter flexible plastic sterile blood bags for storage. Two access points are provided on each side of the habitat, which accommodates five animals per side. Due to the nature of operations on the Space Station – including limited fluid handling – water cannot be changed out weekly as in ground-based vivariums. Water is added to the system a maximum of eighteen months prior to being provided to rodents. The dependable provision of high-quality drinking water is essential for both the welfare of rodents and the scientific integrity of the studies in which they are involved. The robust, multi-stage water preparation process involves the autoclave sterilization of deionized water, the addition of iodine to minimize biofilms, and filtration through a sterile filter to ensure removal of bacteria and other contaminants. The water is then loaded into the sterile blood bags as part of the automated delivery system. A water storage test determined that the shelf life of this water in the habitat could be increased up to four years from a previous eighteen months. This facilitates the ability to pre-position habitats on Station as well as demonstrates that the habitat’s water system can be utilized on future long-duration and deep space missions involving rodents.
Testing and validation of the microbial environment of the NASA rodent spaceflight habitat water delivery system.
Sterilized, deionized water within a closed, self-sufficient system has been used in NASA spaceflight rodent studies for several decades. Within the specialized spaceflight rodent habitat, water is delivered through a compression spring-loaded bag system to maintain positive pressure. Refill of the drinking water occurs every 30 days by direct transfer of potable water from aboard the International Space Station (ISS). This enables long term use without a weekly water change out, which meets spaceflight requirements, but contrasts with the general guidelines for the sanitation of water delivery systems. Even though the water is iodinated to minimize microbial growth, rodents are fed a special diet of high moisture nutrient-rich food bars based on the AIN-93 diet that may contribute to microbial growth in this water system. We designed a ground study to assess the quality of drinking water that is given to rodents throughout a mission. We conducted the ground test using 20 female C57BL/6J mice housed in this specialized habitat to mimic the timeline of a 90-day mission as well as the environmental conditions (temperature, humidity, and pCO2) within the ISS. We used a novel sampling method to test water at 2-week intervals for the 90-days, and also after each 30-day refill of the water delivery system. Mice in standard vivarium cages with water bottles were also included for comparison to the habitat. The results showed that overall microbial load remained close to zero for the duration, while total organic compound concentrations increased from 1370g/L to 10650g/L over the course of 90 days but remained below the level of concern. Inorganic ions and pH were also found to be at acceptable levels. Overall, we conclude that this system is effective in delivering clean, potable water to rodents for the 90-day duration of current missions to the ISS.
Nutrient Stability in NASA Spaceflight Experiment Rodent Food Bars
The nutrient-upgraded Rodent Food Bars (NuRFB) have a long history as the food of choice for NASA Space Shuttle and ISS Rodent Research missions. The NuRFB have previously been assigned an expiration date of two years after production for use in rodent flight experiments aboard the International Space Station (ISS) and three years for ground experiment use when stored between 2°-10°C. The exiguous supply of cold stowage on the ISS necessitated further investigation to determine if NuRFB can be stored at ambient temperatures (AT) without excessive nutrient degradation. The Rodent Research Project Sustaining Engineering Team at the NASA Ames Research Center in Mountain View, CA is responsible for management of this critical flight product.
NASA's Rodent Research Project: Validation of Capabilities for Conducting Long Duration Experiments in Space
Research using rodents is an essential tool for advancing biomedical research on Earth and in space. Prior rodent experiments on the Shuttle were limited by the short flight duration. The International Space Station (ISS) provides a new platform for conducting rodent experiments under long duration conditions. Rodent Research (RR)-1 was conducted to validate flight hardware, operations, and science capabilities that were developed at the NASA Ames Research Center. Twenty C57BL6J adult female mice were launched on Sept 21, 2014 in a Dragon Capsule (SpaceX-4), then transferred to the ISS for a total time of 21-22 days (10 commercial mice) or 37 days (10 validation mice). Tissues collected on-orbit were either rapidly frozen or preserved in RNAlater at -80C (n2group) until their return to Earth. Remaining carcasses on-orbit were rapidly frozen for dissection post-flight. The three controls groups at Kennedy Space Center consisted of: Basal mice euthanized at the time of launch, Vivarium controls housed in standard cages, and Ground Controls (GC) housed in flight hardware within an environmental chamber. Upon return to Earth, there were no differences in body weights between Flight (FLT) and GC at the end of the 37 days in space. Liver enzyme activity levels of FLT mice and all control mice were similar in magnitude to those of the samples that were processed under optimal conditions in the laboratory. Liver samples dissected on-orbit yielded high quality RNA (RIN8.99+-0.59, n7). Liver samples dissected post-flight from the intact, frozen FLT carcasses yielded RIN of 7.27 +- 0.52 (n6). Additionally, wet weights of various tissues were measured. Adrenal glands and spleen showed no significant differences in FLT compared to GC although thymus and livers weights were significantly greater in FLT compared to GC. Over 3,000 tissue aliquots collected post-flight from the four groups of mice were deposited into the Ames Life Science Data Archives for future Biospecimen Sharing Program. Together, the RR validation flight successfully demonstrates the capability to support long-duration experimentation on the ISS to achieve both basic science and biomedical objectives.