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At least 19 records

A methodology for estimating dog noise in an animal housing facility

A rectangular reverberation chamber was designed, constructed and calibrated for the experimental measurement of the sound power level (acoustic power) of a dog. Calibration of the chamber consisted of comparing the acoustic power measured for a random noise source in the chamber with that for the identical source in a free field environment. Data from dogs indicate that barking noise can be modeled as a square wave pattern with short duration and peak sound power levels in the 500 Hz octave band. A-weighted sound pressure levels of up to 114.7 dBA were absorbed, indicating a potential concern for both animals and man chronically exposed to such environments.

Sierens, S. E.↗

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↗

Technology development activities for housing research animals on Space Station Freedom

The development and design of animal facilities are described in terms of the technological needs for NASA's Biological Flight Research Laboratory. Animal habitats are presented with illustrations which encompass waste-collection techniques for microgravity conditions that reduce the need for crew participation. The technology is intended to be highly compatible with animal morphology, and airflow is employed as the primary mechanism of waste control. The airflow can be utilized in the form of localized high-speed directed flow that simultaneously provides a clean animal habitat and low airflow rates. The design of an animal-habitat testbed is presented which capitalizes on contamination-control mechanisms and suitable materials for microgravity conditions. The developments in materials and technologies represent significant contributions for the design of the centrifuge facilities for the Space Station Freedom.

Jenner, Jeffrey W.↗

Social Isolation Impacts Select Responses to Simulated Weightlessness

The rodent hindlimb unloading (HU) model was initially developed to simulate the cephalad fluid shift and musculoskeletal disuse in astronauts. Since then, the HU model has been applied to explore how other systems (e.g. immune, cardiovascular and CNS) respond to weightlessness. Most HU studies are performed with singly-housed animals, although social isolation also can substantially impact behavior and physiology, and therefore may confound HU experimental results. We hypothesized that relative to social housing, single housing exacerbates HU-induced dysfunction in select organ systems. We refined the standard NASA-Ames HU model to accommodate social housing in HU pairs, retaining advantageous features of traditional housing but using commercial off-the-shelf components to facilitate adoption by others. We conducted a 30 day HU experiment with adult, female C57Bl6/NJ mice that were either singly or socially housed. HU animals in both single and social HU housing displayed expected musculoskeletal deficits compared to housing matched, normally loaded (NL) controls. However, select immune, HPA axis, and CNS responses were differentially impacted by the HU social environment relative to NL controls. HU reduced % CD4+ T cells in singly-housed, but not socially-housed mice. Surprisingly, HU increased adrenal gland mass in socially-housed but not singly-housed mice, while social isolation increased adrenal gland mass in NL controls. HU also increased plasma corticosterone levels (day 30) in both singly and socially-housed mice. Thus, the social environment altered select adrenal and immune, but not musculoskeletal, responses to simulated weightlessness. We refine our original hypothesis since our results show combined stressors can mask, not only exacerbate, tissue responses to HU. These findings further expand the utility of the HU model for studying possible combined effects of the various spaceflight stressors.

Tahimic, Candice↗

Development of an Advanced Animal Habitat for Spaceflight

It is necessary to fly a group-housed animals for many Life Science spaceflight studies. Currently, group-housed rodents are flown aboard the shuttle in the Animal Enclosure Module (AEM). Although the AEM has been used successfully for a number of flights, it has significant limitations in the number of animals it can accommodate, limited flight duration, passive temperature control and limited in flight data acquisition capability. An Advanced Animal Habitat (AAH) is being developed, which can be flown on the shuttle middeck, both spacelab and spacehab shuttle payload modules, and the space station. The AAH is designed to house 12 rats or 30 mice for up to 30 days. The AAH will have active temperature control, a window mechanism to facilitate video monitoring/recording of the animals, and biotelemetry capabilities. In addition, the design will permit access to the animals for experimental manipulations in space. The AAH can be refitted to experiment-specific requirements as needed. In initial 7-day hardware tests 12 male rats and 10 female mice show no adverse affects with respect to final body and organ weights as compared to vivarium. controls. The Advanced Animal Habitat will provide the science community opportunities to perform a greater variety of studies for longer duration in the microgravity environment than the current Animal Enclosure Module.

Baer, L.↗

Evaluation of Rodent Spaceflight in the NASA Animal Enclosure Module for an Extended Operational Period (up to 35 days)

The National Aeronautics and Space Administration Animal Enclosure Module (AEM) was developed as a self-contained rodent habitat for shuttle flight missions that provides inhabitants with living space, food, water, ventilation, and lighting for shuttle flight missions, and this study reports whether, after minimal hardware modification, the AEM could support an extended term up to 35 days for Sprague-Dawley rats and C57BL/6 female mice for use on the International Space Station. Success was evaluated based on comparison of AEM housed animals to that of vivarium housed and to normal biological ranges through various measures of animal health and well-being, including animal health evaluations, animal growth and body masses, organ masses, rodent food bar consumption, water consumption, and analysis of blood contents. The results of this study confirmed that the AEMs could support 12 adult female C57BL/6 mice for up to 35 days with self-contained RFB and water, and the AEMs could also support 5 adult male Sprague-Dawley rats for 35 days with external replenishment of diet and water. This study has demonstrated the capability and flexibility of the AEM to operate for up to 35 days with minor hardware modification. Therefore, with modifications, it is possible to utilize this hardware on the International Space Station or other operational platforms to extend the space life science research use of mice and rats.

Animal enclosure module↗

Ames Research Center life sciences payload

In response to a recognized need for an in-flight animal housing facility to support Spacelab life sciences investigators, a rack and system compatible Research Animal Holding Facility (RAHF) has been developed. A series of ground tests is planned to insure its satisfactory performance under certain simulated conditions of flight exposure and use. However, even under the best conditions of simulation, confidence gained in ground testing will not approach that resulting from actual spaceflight operation. The Spacelab Mission 3 provides an opportunity to perform an inflight Verification Test (VT) of the RAHF. Lessons learned from the RAHF-VT and baseline performance data will be invaluable in preparation for subsequent dedicated life sciences missions.

Callahan, P. X.↗

Vitamin D Status in Monkey Candidates for Space Flight

In preparation for the Cosmos 2229 Biosatellite space flight experiments in Rhesus monkeys, we evaluated the status of vitamin D in animals of different origins: candidates for space flight raised in Moscow (IMBP) and animals housed at Ames Research Ctr. (ARC) for pilot studies. Diets at IMBP were natural foods found by analysis to contain 1.4% Ca, 2.8% P and<240 IU D3/kg and at ARC standard monkey chow with 0.9% Ca, 0.5% P and 6600 IU D3/kg. We measured body weights (BW), serum calcium (TCa), total protein (TP), phosphorus (Pi), alkaline phosphatase (AP), 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D) in 16 IMBP and 15 ARC male animals and indices of bone formation in cancellous bone obtained from iliac crest biopsy of 6 IMBP and 13 ARC animals. BW were the same in juveniles at IMBP as ARC although ARC monkeys were born a year later. Mean(1SD) TCa and TP were higher and 25D lower (1819 vs. 93+18 ng/ml,p<.001) in IMBP than ARC animals. 1,25D (174156 vs. 212+77 pg/ml), Pi and AP were similar. In bone, osteoid and osteoblast surfaces averaged 38114% and 33+15% in all, with %vol. of osteoid higher in IMBP than ARC monkeys of the same BW (p<.05) Indices of bone formation were inversely related to 25D, not 1,25D. Of interest are similar 1,25D levels associated with a wide range of substrate and extensive osteoid in bone of D replete animals.

Arnaud, S. B.↗

Simulated Microgravity Affects Behavior and Cytokine Expression in the Hippocampus of Adult Mice: Influence of Mitochondrial Reactive Oxygen Species

The effects of microgravity, and social isolation on the CNS are poorly understood. We hypothesize that mitochondrial reactive oxygen species (ROS) play an important role in this process. Since mice are social animals, our lab developed a novel social model of hindlimb unloading (HU), enabling us to determine the effects of both social isolation and simulated microgravity. Responses to 30d of HU were compared in wildtype or transgenic MCAT mice who over-express human catalase in mitochondria. Abundance of 4-Hydroxynonenal, Park7 (a redox-sensitive chaperone and sensor of oxidative stress) and corticosterone were measured by ELISA. Cytokines related to inflammation in the hippocampus and in plasma were analyzed by a protein array. Behavioral data was collected over a 24-hour period.Socially housed HU mice were more active and conducted at least two times more exploratory activities, compared to normally loaded mice. Correlation analysis revealed that specific brain and plasma cytokines correspond with specific behaviors. Simulated microgravity and/or social isolation caused changes in cytokine patterns in the hippocampus and in plasma, with significant interaction effects of HU and genotype in expression levels of five cytokines (out of 35). Interestingly, elevation of these generally pro-inflammatory cytokines by HU in WT mice was mitigated in MCAT mice, suggesting a role for mitochondrial ROS signaling in inflammatory CNS responses to microgravity. Interestingly, socially housed mice had also lower level of 4HNE and higher level of Park7 in the hippocampus compared to singly housed animals. The cytokine responses to social isolation were more extensive in brain vs plasma. Further, there was no overlap in the cytokine repertoire regulated in response to microgravity versus, isolation suggesting divergent mechanisms or downstream signaling. These findings implicate a potentially important role for mitochondrial ROS in CNS responses to the challenges posed both by prolonged missions in space and bedrest on Earth

Guttmann, Linda↗

Development of a Novel Space Flight Plan to Monitor Female Mice Fertility Using Reduced Crew Time

Ovarian estrogen impacts the normal homeostatic and metabolic processes of all tissues and organ systems within the body: particularly, but not limited to canonical space-flight impacted systems: bone, muscle, immune, wound repair, and cardiovascular. Effects of space flight on the ovarian estrogen production are therefore critical to our understanding of all space flight experiments using female mice, the current paradigm being used on the International Space Station (ISS). Recently, we demonstrated that vaginal wall histology could be used to determine the stage of the estrous cycle in female mice at the time of sacrifice in space. Moreover, this robust technique was completed following two post-flight freezethaw procedures of the carcasses (RR1 experiment). Thus, this technique represents a viable mechanism to determine the estrous cycle status of the female at the time of sacrifice and can be completed in a manner that does not impact primary experimental objectives. We propose that vaginal wall histology become a standard procedure completed on all mice sacrificed in space and that the individual estrous status of each animal be shared with all investigators. While evidence of estrous cyclicity was present in long-term (33 day) RR1 mice, fertility of female mice exposed to weightlessness remains unknown. In preparation for an upcoming funded NASA flight investigating the effects of long duration spaceflight on female fertility, we have refined our experimental design to minimize crew flight time and to accommodate the duration of Dragon capsule berth. These refinements maintain all our proposed primary and secondary experimental objectives. Briefly, in order to evaluate fertility, we will super ovulate mice using standard procedures (PMSG hCG), followed by collection of reproductive tract after follicular stimulation alone (PMSG) or following ovulation (hCG). Ovarian folliculogenesis and ovulation rate will be determined in fixed tissues following return in order to determine fertility. Ovarian and uterine tissues will also be evaluated by hormonal and gene expression profiling using quantitative approaches (radioimmunoassays, western blots, digital droplet PCR). Comparisons will be made to contemporary vivarium and Rodent Research Hardware Transporter and Habitat housed animals maintained on earth. Supported by NNX15AB48G to JST.

Christenson, Lane↗

In-vivo bone strain telemetry in monkeys /M. nemestrina/

A new method for collecting in-vivo bone strain data in monkeys has been developed and tested. The method includes a system which consists of a new design of implantable strain transducer and its companion telemetry package. The transducer fits into a hole drilled in a monkey tibia and is threaded for subsequent bone ingrowth. The transducers and telemetry package are biocompatible for over 503 days. The telemetry package uses Pulse Interval Ratio Modulation (PIRM) to transmit strain information to receiving equipment located outside the animal housing cage.

Young, D. R.↗

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.↗

Physiological Anatomical Rodent Experiment (PARE): 04 Flight Support

Rats were shipped to Kennedy Space Center (KSC), Florida, on day 2 of gestation [(G2) (day 1 = morning on which spermatozoa are present in the vagina)] and laparotomized on G7 to determine the number of implantation sites in each uterine horn. On G8, ten pregnant rats meeting flight criteria (at least five implantation sites each horn) were placed into NASA flight cages (animal enclosure modules, AEMS, five rats per cage), loaded onto the mid-deck of the space shuttle Atlantis, and on G9 (November 3, 1994) they were launched into orbit. On gestation day 20, (November 14, 1994) the shuttle returned to Edwards Air Force Base, California and the flight animals were recovered from the shuttle and subjected to unilateral hysterectomy to provide fetal material from one horn to investigators identified by NASA to study selected fetal parameters. After unilateral hysterectomy, the animals were allowed to recover and deliver vaginally. There were three groups (n = 10 each group) of control animals housed at KSC in the study. A synchronous control group, delayed 24 hours with reference to the flight group, received the same surgeries and was housed five rats per AEM and exposed to all flight conditions (identical temperatures, lighting and humidity) except microgravity. Vivarium control group I did not receive any surgery and was housed in the vivarium in clear polycarbonate cages. Vivarium control group 2 received only a unilateral hysterectomy on day 20 of gestation but otherwise was housed like the vivarium control group 1. Control groups were allowed to complete their pregnancy and deliver fetuses from the remaining horn (Synchronous control and vivarium control group 2) or horns (Vivarium control group 1). After surgery, the dams were euthanized and tissues recovered, and the neonates were assigned to foster dams.

Burden, Hubert W.↗

Disuse bone loss in hindquarter suspended rats: partial weightbearing, exercise and ibandronate treatment as countermeasures

The purpose of this study was to evaluate potential countermeasures for bone loss during long-term space missions in the hindquarter suspended rat, including partial weight bearing (surrogate for artificial gravity) episodic full weight bearing (2 hour/day full weight bearing) and treatment with the third generation bisphosphonate ibandronate (Roche). Graded mechanical loading was studied by housing the animals on a novel servo controlled force plate system which permitted the titration of mechanical force at varying frequency and amplitude and different levels of weight bearing. The force plate, which forms the cage floor, is a glass platform supported by an 18" diameter speaker cone filled with expanding polyurethane foam. An infrared optical sensor attached to the speaker cone yields a voltage linearly related to vertical displacement of the glass platform. The dynamic force on the paw was computed as a product of the apparent mass of the animal on the platform at rest and the acceleration of the platform determined from the second derivative of the optical sensor output. The mass of the animal on the platform was varied by adjusting tension on the tether suspending the animal. Mechanical impact loading was titrated with the force plate resonating at different frequencies, including 3 Hz and 16 Hz.

Non-NASA Center↗

Flying U.S. science on the U.S.S.R. Cosmos biosatellites

The USSR Cosmos Biosatellites are unmanned missions with durations of approximately 14 days. They are capable of carrying a wide variety of biological specimens such as cells, tissues, plants, and animals, including rodents and rhesus monkeys. The absence of a crew is an advantage with respect to the use of radioisotopes or other toxic materials and contaminants, but a disadvantage with respect to the performance of inflight procedures or repair of hardware failures. Thus, experiments hardware and procedures must be either completely automated or remotely controlled from the ground. A serious limiting factor for experiments is the amount of electrical powers available, so when possible experiments should be self-contained with their own batteries and data recording devices. Late loading is restricted to approximately 48 hours before launch and access time upon recovery is not precise since there is a ballistic reentry and the capsule must first be located and recovery vehicles dispatched to the site. Launches are quite reliable and there is a proven track record of nine previous Biosatellite flights. This paper will present data and experience from the seven previous Cosmos flights in which the US has participated as well as the key areas of consideration in planning a flight investigation aboard this Biosatellite platform.

Flight Experiment↗

NASA science utilization plans for the Space Station

The Mir-1 and International Space Station Alpha capabilities present the science community with unique long duration platforms to conduct a wide range of scientific research in the microgravity and life sciences as well as in the observational sciences, NASA is developing plans to use the capabilities of Mir and Space Station as they emerge during the development of the orbital program. In both cases the planned science utilization programs take advantage of the volume, crew, power, microgravity and logistics resupply unique to each phase. The paper will present these utilization plans in the context of an evolving scientific program.

manned↗