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At least 1,423 records · Page 79

Effect of spaceflight on lymphocyte proliferation and interleukin-2 production

In this study, inguinal lymp node lymphocytes from rats flown on the Cosmos 2044 mission were tested for proliferation and interleukin-2 (IL-2) production. Cells cultured with mitogenic lectins, phorbol ester, and calcium ionophore, or T-cell mitogen and lymphokine, were assayed for DNA synthesis by (H-3) thymidine incorporation. Lymphocytes incubated with a T-cell mitogen alone also were tested for IL-2 production. Proliferation of lymphocytes from flight rats was not significantly different from controls for any of the mitogens tested. Furthermore, lymph node lymphocytes from control and flown rats produced similar amounts of IL-23. Thus microgravity may act on lymphocytes in a tissue-specific manner, a new finding that could impact on the evaluation of spaceflight effects on immunocompetence.

Nash, Patricia V.↗

Toxicity study of dimethylethoxysilane (DMSES), the waterproofing agent for the Orbiter heat protective system

DMES, a volatile liquid, is used by NASA to waterproof the Orbiter thermal protective system. During waterproofing operations at the Oribter Processing Facility at KSC, workers could be exposed to DMES vapor. To assess the toxicity of DMES, acute and subchronic (2-week and 13-week) inhalation studies were conducted with rats. Studies were also conducted to assess the potential of DMES. Inhalation exposure concentrations ranged from 40 ppm to 4000 ppm. No mortality was observed during the studies. Exposures to 2100 ppm produced narcosis and ataxia. Post-exposure recovery from these CNS effects was rapid (less than 1 hr). These effects were concentration-dependent and relatively independent of exposure length. Exposure to 3000 ppm for 2 weeks (5 h/d, 5 d/wk) produced testicular toxicity. The 13-week study yielded similar results. Results from the genotoxicity assays (in vivo/in vitro unscheduled DNA synthesis in rat primary heptaocytes, chromosomal aberrations in rat bone marrow cells; reverse gene mutation in Salmonella typhimurium; and forward mutation in Chinese hamster culture cells) were negative. These studies indicated that DMES is mildly to moderately toxic but not a multagen.

Lam, Chiu-Wing↗

The effects of area postrema lesions and selective vagotomy on motion-induced conditioned taste aversion

Conditioned taste aversion (CTA) is one of several behaviors which was suggested as a putative measure of motion sickness in rats. A review is made of studies which used surgical disruption of area postrema or the vagus nerve to investigate whether CTA and vomiting induced by motion may depend on common neural pathways or structures. When the chemoreceptive function of the area postrema (AP) is destroyed by complete ablation, rats develop CTA and cats and monkeys develop CTA and vomit. Thus the AP is not crucially involved in either CTA or vomiting induced by motion. However, after complete denervation of the stomach or after labyrinthectomy rats do not develop CTA when motion is used as the unconditioned stimulus. Studies of brainstem projections of the vagus nerve, the area postrema, the periaqueductal grey, and the vestibular system are used as the basis for speculation about regions which could mediate both motion-induced vomiting and behavioral food aversion.

conditioned taste aversion↗

Role of lateral parabrachial nucleus in the inhibition of water intake produced by right atrial stretch

Rats with either bilateral electrolytic or sham lesions of the ventrolateral portion of the lateral parabrachial nucleus (VLLPBN) were implanted with latex balloons that lay at the right superior vena cava/atrial junction (RSVC/AJ). Water intake in response to isoproterenol was measured both with and without inflation of the balloon. Water intake of the sham-lesioned rats was significantly depressed by balloon inflation during the first hour of the experiment. In contrast, water intake in the VLLPBN-lesioned rats was unaffected by balloon inflation. These results suggest that the VLLPBN is involved in the processing of afferent input from stretch-activated RSVC/AJ receptors.

Ohman, Lynne E.↗

Regulation of Blood Volume During Spaceflight

The effects of spaceflight on erythropoiesis and blood volume in the rat were studied during the 14-day NASA Spacelab Life Sciences 2 (SLS-2) Shuttle mission. Measurements included red blood cell mass (RBCM), plasma volume (PV), iron utilization and iron utilization in response to an injection of erythropoietin. Red blood cell (RBC) survival, splenic sequestration and erythrocyte morphology were also evaluated. At landing, the RBCM adjusted for body weight was significantly lower in the flight animals than in the ground controls. While the PV was also decreased, the change was not statistically significant. Incorporation of iron into circulating RBCs was normal when measured after five days of spaceflight and the rat responded normally to the single in-flight injection of erythropoietin. No change in RBC morphology could be attributed to spaceflight. A normal survival was found for the RBC population that was represented by Cr-51 labeled RBCS. These results demonstrate that rats, like humans, return from spaceflight with a decreased RBCM and total blood volume.

Alfrey, Clarence P.↗

Role of Corticosteroids in Bone Loss During Space Flight

The primary objective of this research project is to test the hypothesis that corticosteroids contribute to the adverse skeletal effects of space flight. To achieve this objective, serum corticosteroids, which are known to increase during space flight, must be maintained at normal physiologic levels in flight rats by a combination of adrenalectomy and corticosteroid supplementation via implanted hormone pellets. Bone analyses in these animals will then be compared to those of intact flight rats that, based on past experience, will undergo corticosteroid excess and bone loss during space flight. The results will reveal whether maintaining serum corticosteroids at physiologic levels in flight rats affects the skeletal abnormalities that normally develop during space flight. A positive response to this question would indicate that the bone loss and decreased bone formation associated with space flight are mediated, at least in part, by corticosteroid excess.

Wronski, Thomas J.↗

Animal Enclosure Module (AEM)

The primary objective of this research project is to test the hypothesis that corticosteroids contribute to the adverse skeletal effects of space flight. To achieve this objective, serum corticosteroids, which are known to increase during space flight, must be maintained at normal physiologic levels in flight rats by a combination of adrenalectomy and corticosteroid supplementation via implanted hormone pellets. Bone analyses in these animals will then be compared to those of intact flight rats that, based on past experience, will undergo corticosteroid excess and bone loss during space flight. The results will reveal whether maintaining serum corticosteroids at physiologic levels in flight rats affects the skeletal abnormalities that normally develop during space flight. A positive response to this question would indicate that the bone loss and decreased bone formation associated with space flight are mediated, at least in part, by corticosteroid excess.

Source record↗

STS-90 Day 15 Highlights

On this fifteeth day of the STS-90 mission, the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk turns its attention to dexterity tests and dissections of rats neonates and the ball-catch experiment. Mission Specialists Rick Linnehan and Dave Williams and Payload Specialist Jim Pawelczyk will dissect the newborn rats. The dexterity test will test the response of young rats as they are tilted and turned while walking and climbing on a special apparatus with various surfaces. Later, all four payload crew members will repeat the ball-catch experiment. This experiment studies the ability of the central nervous system to accept and interpret new stimuli in space. The astronauts have performed this test at various points in the mission so scientists can compare their responses as their bodies adapt to weightlessness.

Source record↗

Gravity and Skeletal Growth

Two simultaneous experiments were performed using 5-week-old male Sprague Dawley rats; in one study, the rats were flown in low earth orbit; in the other study, the hindlimbs of the growing rats were elevated to prevent weight bearing. Following 9 d of unloading, weight bearing was restored for 4, 28, and 76 hrs. Afterwards, additional hindlimb unloading experiments were performed to evaluate the skeletal response to 0, 2, 4, 6, 8, 10, 12, 16, and 24 hrs of restored weight bearing following 7 d of unloading. Cancellous and cortical bone histomorphometry were evaluated in the left tibia at the proximal metaphysis and in the left femur at mid-diaphysis, respectively. Steady-state mRNA levels for bone matrix proteins and skeletal signaling peptides were determined in total cellular RNA extracted from trabeculae from the right proximal tibiametaphysis and periosteum from the right femur. Spaceflight and hindlimb unloading each resulted in cancellous osteopenia, as well as a tendency towards decreased periosteal bone formation. Both models for skeletal unloading resulted in site specific reductions in mRNA levels for transforming growth factor-beta (sub 1) (TGF-beta) osteocalcin (OC), and prepro-alpha (I) subunit of type 1 collagen (collagen) and little or no changes in mRNA levels for glyceraldehyde-3-phosphate dehydrogenase (GAP) and insulin-like growth factor I (IGF-I). Restoration of normal weight bearing resulted in transient increases in mRNA levels for the bone matrix proteins and TGF-beta in the proximal metaphysis and periosteum and no changes in either GAP or IGF-I mRNA levels. The timecourse for the response differed between the two skeletal compartments; the tibial metaphysis responded much more quickly to reloading. These results suggest that the skeletal adaptation to acute physiological changes in mechanical usage are mediated, in part, by changes in mRNA levels for bone matrix proteins and TGF-beta.

Morey-Holton, Emily↗

Alterations in Skeletal Muscle Function with Microgravity, and the Protective Effects of High Resistance Isometric and Isotonic Exercise

Exposure to microgravity or models designed to mimic the unloaded condition, such as bed rest in humans and hindlimb unloading (HU) in rats leads to skeletal muscle atrophy, a loss in peak force and power, and an increased susceptibility to fatigue. The posterior compartment muscles of the lower leg (calf muscle group) appear to be particularly susceptible. Following only 1 wk in space or HU, rat soleus muscle showed a 30 to 40% loss in wet weight. After 3 wk of HU, almost all of the atrophied soleus fibers showed a significant increase in maximal shortening velocity (V(sub 0)), while only 25 to 30 % actually transitioned to fast fibers. The increased V(sub 0), was protective in that it reduced the decline in peak power associated with the reduced peak force. When the soleus is stimulated in situ following HU or zero-g one observes an increased rate and extent of fatigue, and in the former the increased fatigue is associated with a more rapid depletion of muscle glycogen and lactate production. Our working hypothesis is that following HU or spaceflight in rats and bed rest or spaceflight in humans limb skeletal muscles during contractile activity depend more on carbohydrates and less on fatty acids for their substrate supply. Baldwin et al. found 9 days of spaceflight to reduce by 37% the ability of both the high and low oxidative regions of the vastus muscle to oxidize long-chain fatty acids. This decline was not associated with any change in the enzymes of the tricarboxylic acid cycle or oxidation pathway. The purpose of the current research was to establish the extent of functional change in the slow type I and fast type H fibers of the human calf muscle following 17 days of spaceflight, and determine the cellular mechanisms of the observed changes. A second goal was to study the effectiveness of high resistance isotonic and isometric exercise in preventing the deleterious functional changes associated with unloading.

Fitts, R. H.↗

Circadian Behavioral Study: LED vs Cool White Fluorescent - 0.1, 1, 10, 40, 80 lux

Currently, the light source most commonly used in animal habitat lighting is cool white fluorescent (CWF) light. It was the objective of this study to evaluate a novel LED light source for use in animal habitat lighting by comparing its effectiveness to CWF light in producing and maintaining a normal circadian entrainment. The LED and CWF lights had similar spectral power distributions. Sprague-Dawley rats (175-350 g) were kept individually in metabolic cages, under a strict lighting control: 4 days of acclimation at 12:12 LD, 14 days of 12:12 LD, 14 days of 24:0 LD (free-run), and finally 12:12 LD. Food and water were provided ad libitum. Three behavioral parameters were monitored continuously: gross locomotor activity, drinking, and feeding. Combined mean free run periods (tau) were (mean +/- SEM): 24.6 +/- 0.1 and 24.7 +/- 0.2 at 0.1 lux, 25.5 +/- 0.1 and 25.7 +/- 0.1 at 1.0 lux, 25.3 +/- 0.2 and 25.4 +/- 0.2 at 10 lux, 25.8 +/- 0.1 and 25.9 +/- 0.1 at 40 lux, and 25.9 +/- 0.1 and 25.9 +/- 0.1 at 80 lux, CWF and LED respectively. ANOVA found a significant effect (p < 0.05) due to light level, but no difference in tau between rats exposed to constant CWF light and rats exposed to constant LED light. This study has shown that LED light can produce the same entrainment pattern as a conventional CWT light at similar intensities (0.1, 1, 10, 40, and 80 lux). LED light sources may be a suitable replacement for conventional light sources used in animal habitat lighting while providing many mechanical and economical advantages.

Holley, Daniel C.↗

Effects of Age on Temperature Responses During Exposure to Hypergravity

Rats subjected to centrifugation show a marked decrease in body temperature relating to gravity level. Several studies have indicated, that an initial response to centrifugation is followed by acclimation. To test for differences between young (Y; 2 months) and mature (M; 8 months) rats in their response in temperature, both groups were exposed to hypergravity induced by centrifugation. Thirty-six male rats were divided into four groups according to age and G-load (control (1.0G-Y and 1.0G-M), 2.0G-Y or 2.0G-M) and were housed in pairs in standard vivarium cages. During the 7-day period of centrifugation, temperature was measured every five minutes by surgically implanted telemeters. Body mass was measured daily. We found that initial body temperature in 2.0G-M was less than that of 2.0G-Y. Both hypergravity groups (2.0G-Y and 2.0G-M) showed a decrease in temperature at the onset of centrifugation, and the change in temperature (Delta = 0.5 C) remained the same between the groups. Significant differences persisted with 2.0G-Y recovering to control values in four days and 2.0G-M recovering in five days. These results indicate that the mature animals have a similar response as the younger animals, but take longer to acclimate.

Fung, C.K.↗

Effects of Growth Hormone/IGF-I and Exercise on Unloaded Bones

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) in combination with exercise prevent muscle atrophy induced by unloading in the tail-suspension rat model for space flight (Gosselink et al, FASEB J 1994). This study evaluated the effects of these treatments on bone. Hypophysectomized rats were suspended (S) and treated with 1mg/kg/day CH plus IGF-I (H) or vehicle (Sal) daily by injection and exercised (Ex) by 3 climbs up a 1m ladder carrying a load equal to 30% the initial body weight (BW) 3x/day for 10 days. Tibial epiphysis (Epi) widths were measured by micrometry and femoral Bone Mineral Content (fBMC) in excised femurs by DEXA (Lunar DPX-L). Serum calcium (Ca) and phosphorus (Pi) were measured by COBAS Autoanalyzer (Roche Diag.). Ambulatory (Amb)-H treated rats showed growth rates of 6.6+-0.9 g/day, similar to S-H-Ex and higher than S-H (3.210.6, p less than 0.05) and S-Sal (-0.711.0, p less than 0.05). Epi widths were 10% lower in S-Sal, and S-Sal-Ex, and increased 100% in all H groups. fBMC was less in S than Amb, only when all S groups are compared to both Amb groups (p less than 0.03). H treatment increased fBMC (p less than 0.05) but reduced fBMC/100g BW in all H groups (p less than 0.001). The reduced density of H bone cannot be attributed to low circulating Ca. and Pi since they were higher in H than Sal (p less than 0.001). H treatment for 10 days in doses sufficient to support normal growth in BW failed to produce normal Epi widths or fBMC, even when combined with exercise. The suspension effect observed in Epi widths was not corrected by H or Ex alone, but was improved by H plus a This regimen. although effective in preventing muscle atrophy, failed to return bone measures, Epi widths and fBMC, to normal.

Harper, J. S.↗

Light-Emitting Diodes (LED) for Primary Animal Habitat Lighting in Highly Controlled Environments

Significant alterations in Biological Clock responses have been reported following sidereal time changes (e.g., Jet-lag), and exposure to microgravity (e.g., daytime sleepiness). Additionally, light reduces circulating melatonin (spectral specificity greatest between 450-500 nm). It was hypothesized that LEDs can replace the current light sources used in zero gravity and terrestrial research laboratories because of their small size, low mass, low energy consumption and long functional life. This report evaluates the capacity of LEDs to entrain the circadian system of rats as judged by measurement of overt behavioral circadian rhythms (activity, feeding, drinking). These data were collected in highly controlled environments similar to the shuttle Animal Enclosure Modules. Two groups were compared: control - animals exposed to standard cool-white fluorescent lights, and test - animals exposed to LEDs with a spectral power distribution matching the fluorescent lights. Gross locomotor activity, feeding and drinking frequencies were continuously monitored and stored at 10 minute intervals. Animals were exposed to the following photoperiods: 28 days of 12L:12D, 19 days of 24L:0D and 16 days of 12L:12D. Light intensities tested varied between 0.1 to 100 lux. Rats received food and water ad libitum, and temperature and humidity were controlled throughout the study. The general health status of all rats was acceptable for each day of this study. No incidents of aggressive behavior were observed. Growth, locomotor activity, food and water consumption were comparable for all groups of animals, i.e, the circadian characteristics of the animals under these conditions were comparable. These results indicate that LED arrays are as effective in maintaining circadian rhythm stability as the commonly used cool-white fluorescent light sources. LEDs with their flexible spectrum, low energy requirements and minimal heat production have advantages for some chronopharmacology studies and for microgravity animal habitats.

Winget, C. M.↗

Understanding Fluid Shifts in the Brain: Choroidal Regulation Involved in the Cerebral Fluid Response to Altered Gravity

Fluid balance and regulation of body fluid production are critical aspects of life and survival on Earth. In space, without gravity exerting its usual downward pulling effect, the fluids of the human body shift in an unnatural, headward direction. After awhile, humans and other mammalian species adapt to the microgravity environment which leads to changes in the regulation and distribution of these body fluids. Previous spaceflight experiments have indicated that production of fluid in the brain and spinal cord, cerebrospinal fluid (CSF), might be reduced in rats exposed to microgravity. In this experiment conducted by Dr. Jacqueline Gabrion (University of Pierre and Marie Curie, France), proteins important for CSF production, and several molecules that regulate water and mineral transport, will be investigated in rats flown on the Shuttle. Dr. Gabrion and her team will determine the amounts of these proteins and molecules present in the brain in order to evaluate whether any changes have taken place during the rats' adaptation to microgravity. The levels of different aquaporins (proteins that act as a channel for water transport in and out of cells) will also be investigated in other areas of the brain and body to better understand the regulatory responses affecting these important water channel proteins. In addition to producing essential and basic information about fluid production in the brain and body, this experiment will reveal fundamental information about the mechanisms involved in cerebral adaptation and fluid balance during spaceflight.

Gabrion, Jaqueline↗

The Effect of Spaceflight on the Ultrastructure of the Cerebellum

In weightlessness, astronauts and cosmonauts may experience postural illusions as well as motion sickness symptoms known as the space adaptation syndrome. Upon return to Earth, they have irregularities in posture and balance. The adaptation to microgravity and subsequent re-adaptation to Earth occurs over several days. At the cellular level, a process called neuronal plasticity may mediate this adaptation. The term plasticity refers to the flexibility and modifiability in the architecture and functions of the nervous system. In fact, plastic changes are thought to underlie not just behavioral adaptation, but also the more generalized phenomena of learning and memory. The goal of this experiment was to identify some of the structural alterations that occur in the rat brain during the sensory and motor adaptation to microgravity. One brain region where plasticity has been studied extensively is the cerebellar cortex-a structure thought to be critical for motor control, coordination, the timing of movements, and, most relevant to the present experiment, motor learning. Also, there are direct as well as indirect connections between projections from the gravity-sensing otolith organs and several subregions of the cerebellum. We tested the hypothesis that alterations in the ultrastructural (the structure within the cell) architecture of rat cerebellar cortex occur during the early period of adaptation to microgravity, as the cerebellum adapts to the absence of the usual gravitational inputs. The results show ultrastructural evidence for neuronal plasticity in the central nervous system of adult rats after 24 hours of spaceflight. Qualitative studies conducted on tissue from the cerebellar cortex (specifically, the nodulus of the cerebellum) indicate that ultrastructural signs of plasticity are present in the cerebellar zones that receive input from the gravity-sensing organs in the inner ear (the otoliths). These changes are not observed in this region in cagematched ground control animals. The specific changes include the formation of lamellar bodies, profoundly enlarged Purkinje cell mitochondria, the presence of inter-neuronal cellular protrusions in the molecular layer, and signs of degeneration in the distal dendrites of the Purkinje cells. Since these morphologic signs are not apparent in the control animals, they are not likely to be due to caging or tissue processing effects. The particular nature of the structural alterations in the nodulus, most notably the formation of lamellar bodies and the presence of degeneration, further suggests that excitotoxicity (damaging overstimulation of neurons) may play a role in the short-term neural response to spaceflight. These findings suggest a structural basis for the neuronal and synaptic plasticity accompanying the central nervous system response to altered gravity and help identify the cellular bases underlying the vestibular abnormalities experienced by astronauts during periods of adaptation and re-adaptation to different gravitational forces. Also, since the short- and long-term changes in neural structure occurring during such periods of adaptation resemble the neuronal alterations that occur in some neurologic disorders such as stroke, these findings may offer guidance in the development of strategies for rehabilitation and treatment of such disorders.

Holstein, Gay R.↗

Nitric Oxide Signaling in Hypergravity-Induced Neuronal Plasticity

The goal of this research project was to identify the neurons and circuits in the vestibular nuclei and nucleus prepositus hypoglossi that utilize nitric oxide (NO) for intercellular signaling during gravity-induced plasticity. This objective was pursued using histochemical and immunocytochemical approaches to localize NO-producing neurons and characterize the fine morphology of the cells in ground-based studies of normal rats, rats adapted to hypergravity, and rats adapted to hypergravity and then re-adapted to the 1G environment. NO-producing neurons were identified and studied using four methodologies: i) immunocytochemistry employing polyclonal antibodies directed against neuronal nitric oxide synthase (nNOS), to provide an indication of the capacity of a cell for NO production; ii) immunocytochemistry employing a monoclonal antibody directed against L-citrulline, to provide an indirect index of the enzyme's activity; iii) histochemistry based on the NADPH-diaphorase reaction, for fuI1 cytological visualization of neurons; and iv) double immunofluorescence to co-localize nNOS and L-citrulline in individual vestibular nuclei (VN) and neurons.

Holstein, Gay R.↗

Regulation of sympathetic nervous system function after cardiovascular deconditioning

Humans subjected to prolonged periods of bed rest or microgravity undergo deconditioning of the cardiovascular system, characterized by resting tachycardia, reduced exercise capability, and a predisposition for orthostatic intolerance. These changes in cardiovascular function are likely due to a combination of factors, including changes in control of body fluid balance or cardiac alterations resulting in inadequate maintenance of stroke volume, altered arterial or venous vascular function, reduced activation of cardiovascular hormones, and diminished autonomic reflex function. There is evidence indicating a role for each of these mechanisms. Diminished reflex activation of the sympathetic nervous system and subsequent vasoconstriction appear to play an important role. Studies utilizing the hindlimb-unloaded (HU) rat, an animal model of deconditioning, evaluated the potential role of altered arterial baroreflex control of the sympathetic nervous system. These studies indicate that HU results in blunted baroreflex-mediated activation of both renal and lumbar sympathetic nerve activity in response to a hypotensive stimulus. HU rats are less able to maintain arterial pressure during hemorrhage, suggesting that diminished ability to increase sympathetic activity has functional consequences for the animal. Reflex control of vasopressin secretion appears to be enhanced following HU. Blunted baroreflex-mediated sympathoexcitation appears to involve altered central nervous system function. Baroreceptor afferent activity in response to changes in arterial pressure is unaltered in HU rats. However, increases in efferent sympathetic nerve activity for a given decrease in afferent input are blunted after HU. This altered central nervous system processing of baroreceptor inputs appears to involve an effect at the rostral ventrolateral medulla (RVLM). Specifically, it appears that tonic GABAA-mediated inhibition of the RVLM is enhanced after HU. Augmented inhibition apparently arises from sources other than the caudal ventrolateral medulla. If similar alterations in control of the sympathetic nervous system occur in humans in response to cardiovascular deconditioning, it is likely that they play an important role in the observed tendency for orthostatic intolerance. Combined with potential changes in vascular function, cardiac function, and hypovolemia, the predisposition for orthostatic intolerance following cardiovascular deconditioning would be markedly enhanced by blunted ability to reflexly activate the sympathetic nervous system.

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