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All sourcesNASA NTRSDOE OSTI
NASA NTRS1985

Muscle protein and glycogen responses to recovery from hypogravity and unloading by tail-cast suspension

Previous studies in this laboratory using the tail-bast hindlimb suspension model have shown that there are specific changes in protein and carbohydrate metabolism in the soleus muscle due to unloading. For example, 6 days of unloading caused a 27% decrease in mass and a 60% increase in glycogen content in the soleus muscle, while the extensor digitorum longus muscle was unaffected. Also, fresh tissue tyrosine and its in vitro release from the muscle are increased in the unloaded soleus, indicating that this condition causes a more negative protein balance. With these results in mind, studies to investigate the effect of hypogravity on protein and carbohydrate metabolism in a number of rat hindlimb muscles were carried out.

Henriksen, E. J.↗
NASA NTRS1985

Muscle protein and glycogen responses to recovery from hypogravity and unloading by tail-cast suspension

Previous studies in this laboratory using the tail-bast hindlimb suspension model have shown that there are specific changes in protein and carbohydrate metabolism in the soleus muscle due to unloading. For example, 6 days of unloading caused a 27 percent decrease in mass and a 60 percent increse in glycogen content in the soleus muscle, while the extensor digitorum longus muscle was unaffected. Also, fresh tissue tyrosine and its in vitro release from the muscle are increased in the unloaded soleus, indicating that this condition causes a more negative protein balance. With these results in mind, studies to investigate the effect of hypogravity on protein and carbohydrate metabolism in a number of rat hindlimb muscles were carried out.

Henriksen, E. J.↗
NASA NTRS1994

Metabolic myopathies

Metabolic myopathies are disorders of muscle energy production that result in skeletal muscle dysfunction. Cardiac and systemic metabolic dysfunction may coexist. Symptoms are often intermittent and provoked by exercise or changes in supply of lipid and carbohydrate fuels. Specific disorders of lipid and carbohydrate metabolism in muscle are reviewed. Evaluation often requires provocative exercise testing. These tests may include ischemic forearm exercise, aerobic cycle exercise, and 31P magnetic resonance spectroscopy with exercise.

Review↗
NASA NTRS1978

The Effects of Space Flight on Some Liver Enzymes Concerned with Carbohydrate and Lipid Metabolism in Rats

The activities of about 30 enzymes concerned with carbohydrate and lipid metabolism and the levels of glycogen and of individual fatty acids were measured in livers of rats ex- posed to prolonged space flight (18.5 days) aboard COSMOS 986 Biosatellite. When flight stationary, (FS) and flight centrifuged (FC) rats were compared at recovery (R(sub 0)), decrceases in the activities of glycogen phosphorylase, alpha glycerphosphate, acyl transferase, diglyceride acyl transferase, acconitase and Epsilon-phosphogluconate dehydrogenase were noted in the weightless group (FS). The significance of these findings was strengthened since all activities, showing alterations at R(sub 0), returned to normal 25 days post-flight. Differences were also seen in levels of two liver constituents. When glycogen and total fatty acids of the two groups of flight animals were determined, differences that could be attributed to reduced gravity were observed, the FS group at R(sub 0) contained, on the average, more than twice the amount of glycogen than did controls ad a remarkable shift in the ratio of palmitate to palmitoleate were noted. These metabolic alterations appear to be unique to the weightless condition. Our data justify the conclusion that centrifugation during space flight is equivalent to terrestrial gravity.

Abraham, S.↗
NASA NTRS1995

Hypervolemia from Drinking Hyperhydration Solutions at Rest and Exercise

The mechanism of muscular fatigue from physical work and exercise (high metabolism) is not clear, but involves disturbances of muscle surface membrane excitation-contraction coupling from changes in sarcoplasmic reticulum Ca2+ release, cell H+ and Pi responses, and carbohydrate metabolism. Fatigue in people at rest (low metabolism) involves both psychological and physiological factors, probably in different proportions. One common factor appears to be the level and distribution of water and electrolytes within muscle cells and other vascular, interstitial, body fluid compartments. The vascular fluid volume, composed of plasma and red blood cells, is a primary regulatory factor for cardiovascular function; reduction of vascular volume (hypovolemia) and total body water (hypohydration) adversely affect exercise performance. Plasma volume and plasma ionic-osmotic constituent concentrations are also regulatory factors for body thermoregulation, which is often compromised from exercise induced hypovolemia and hypohydration. Rehydration of dehydrated people on earth is relatively easy with appropriate food (osmols), fluid, and a restful environment. But ad libitum drinking under stressful conditions; e.g., heat, exercise, or prior dehydration, results in involuntary dehydration defined as the delay in full fluid replacement (euhydration) during and following loss of body fluid. Astronauts, with their reduced total body water are euhydrated while in weightlessness, but become "dehydrated" during reentry and landing. Thus, people subjected to acute or chronic stress are probably somewhat "dehydrated" as well as fatigued. Many rehydration drinks are more concentrated (hypertonic-hyperosmotic) with respect to the normal plasma osmolality of 285 mOsm/kg H2O and more of the drink osmols are contributed by carbohydrates than by ionized substances. There have been few studies on the efficacy of various drink formulations for increasing body fluid compartment volumes, especially plasma volume, in rested hydrated subjects. Recent findings from our laboratory have indicated that drinks containing greater concentrations of ionized substances (Performance 1 and AstroAde) up to 157 mEq/L Na+ induced greater levels of hypervolemia in resting, moderately dehydrated men, and were also better than water for attenuating the characteristic hypovolemia during supine, submaximal, leg ergometer exercise.

Greenleaf, John E.↗
NASA NTRS1992

The role of pyridoxine as a countermeasure for in-flight loss of lean body mass

Ground based and in flight research has shown that humans, under conditions of microgravity, sustain a loss of lean body tissue (protein) and changes in several biological processes including, reductions in red blood cell mass, and neurotransmitters. The maintenance of muscle mass, the major component of lean body mass, is required to meet the needs of space station EVAs. Central to the biosynthesis of amino acids, the building blocks of protein, is pyridoxine (vitamin B-6). Muscle mass integrity requires the availability of vitamin B-6 for protein metabolism and neurotransmitter synthesis. Furthermore, the formation of red blood cells require pyridoxine as a cofactor in the biosynthesis of hemoglobin, a protein that carries oxygen to tissues. In its active form, pyridoxal-5'-phosphate (PLP), vitamin B-6 serves as a link between amino acid and carbohydrate metabolism through intermediates of glycolysis and the tricarboxylic acid cycle. In addition to its role in energy metabolism, PLP is involved in the biosynthesis of hemoglobin and neurotransmitter which are necessary for neurological functions. Alterations in pyridoxine metabolism may affect countermeasures designed to overcome some of these biochemical changes. The focus of this research is to determine the effects of microgravity on the metabolic utilization of vitamin B-6, integrating nutrition as an integral component of the countermeasure (exercise) to maintain lean body mass and muscle strength. The objectives are: 1) to determine whether microgravity effects the metabolic utilization of pyridoxine and 2) to quantitate changes in B-6 vitamer distribution in tissue and excreta relative to loss of lean body tissue. The rationale for this study encompasses the unique challenge to control biochemical mechanisms effected during space travel and the significance of pyridoxine to maintain and counter muscle integrity for EVA activities. This experiment will begin to elucidate the importance of biochemical interactions between micronutrients and the homeostasis condition of biological processes in the space environment. To address this research topic a simulated microgravity model has been developed. The experiment uses radioisotopically labelled pyridoxine administered as an oral dose to rats which are maintained by tail suspension to simulate a microgravity environment. At the termination of the study, liver, muscle, blood and urine are collected and analyzed by reverse phase high pressure liquid chromatography to determine the quantity and distribution of the B-6 vitamers in tissue and excreta relative to lean body tissue loss. Earlier studies, published by this investigator, have shown that differences in vitamer distribution among samples from experimental versus control subjects indicate changes in metabolic utilization and storage of vitamin B-6.

Gilbert, Joyce A.↗
NASA NTRS1981

The effects of space flight on some rat liver enzymes regulating carbohydrate and lipid metabolism

The effects of space flight conditions on the activities of certain enzymes regulating carbohydrate and lipid metabolism in rat liver are investigated in an attempt to account for the losses in body weight observed during space flight despite preflight caloric consumption. Liver samples were analyzed for the activities of 32 cytosolic and microsomal enzymes as well as hepatic glycogen and individual fatty acid levels for ground control rats and rats flown on board the Cosmos 936 biosatellite under normal space flight conditions and in centrifuges which were sacrificed upon recovery or 25 days after recovery. Significant decreases in the activities of glycogen phosphorylase, alpha-glycerol phosphate acyl transferase, diglyceride acyl transferase, aconitase and 6-phosphogluconate dehydrogenase and an increase in palmitoyl CoA desaturase are found in the flight stationary relative to the flight contrifuged rats upon recovery, with all enzymes showing alterations returning to normal values 25 days postflight. The flight stationary group is also observed to be characterized by more than twice the amount of liver glycogen of the flight centrifuged group as well as a significant increase in the ratio of palmitic to palmitoleic acid. Results thus indicate metabolic changes which may be involved in the mechanism of weight loss during weightlessness, and demonstrate the equivalence of centrifugation during space flight to terrestrial gravity.

Abraham, S.↗
NASA NTRS1988

Physiology of prolonged bed rest

Bed rest has been a normal procedure used by physicians for centuries in the treatment of injury and disease. Exposure of patients to prolonged bed rest in the horizontal position induces adaptive deconditioning responses. While deconditioning responses are appropriate for patients or test subjects in the horizontal position, they usually result in adverse physiological responses (fainting, muscular weakness) when the patient assume the upright posture. These deconditioning responses result from reduction in hydrostatic pressure within the cardiovascular system, virtual elimination of longitudinal pressure on the long bones, some decrease in total body metabolism, changes in diet, and perhaps psychological impact from the different environment. Almost every system in the body is affected. An early stimulus is the cephalic shift of fluid from the legs which increases atrial pressure and induces compensatory responses for fluid and electrolyte redistribution. Without countermeasures, deterioration in strength and muscle function occurs within 1 wk while increased calcium loss may continue for months. Research should also focus on drug and carbohydrate metabolism.

Greenleaf, J. E.↗
NASA NTRS1996

Cytochemical localization of reserves during seed development in Arabidopsis thaliana under spaceflight conditions

Successful development of seeds under spaceflight conditions has been an elusive goal of numerous long-duration experiments with plants on orbital spacecraft. Because carbohydrate metabolism undergoes changes when plants are grown in microgravity, developing seed storage reserves might be detrimentally affected during spaceflight. Seed development in Arabidopsis thaliana plants that flowered during 11 d in space on shuttle mission STS-68 has been investigated in this study. Plants were grown to the rosette stage (13 d) on a nutrient agar medium on the ground and loaded into the Plant Growth Unit flight hardware 18 h prior to lift-off. Plants were retrieved 3 h after landing and siliques were immediately removed from plants. Young seeds were fixed and processed for microscopic observation. Seeds in both the ground control and flight plants are similar in their morphology and size. The oldest seeds from these plants contain completely developed embryos and seed coats. These embryos developed radicle, hypocotyl, meristematic apical tissue, and differentiated cotyledons. Protoderm, procambium, and primary ground tissue had differentiated. Reserves such as starch and protein were deposited in the embryos during tissue differentiation. The aleurone layer contains a large quantity of storage protein and starch grains. A seed coat developed from integuments of the ovule with gradual change in cell composition and cell material deposition. Carbohydrates were deposited in outer integument cells especially in the outside cell walls. Starch grains decreased in number per cell in the integument during seed coat development. All these characteristics during seed development represent normal features in the ground control plants and show that the spaceflight environment does not prevent normal development of seeds in Arabidopsis.

STS-68 Shuttle Project↗
NASA NTRSDate not supplied

One-Carbon Metabolism and SANS 2022 Update

Spaceflight Associated Neuro-ocular Syndrome, or SANS, affects a subset of astronauts (1, 2), and biochemical evidence has documented differences in those astronauts (3). Specifically, they had higher circulating concentrations of metabolites of the one-carbon metabolic pathway (1C), including homocysteine, and these concentrations were higher before flight (3). After ruling out many potential confounding factors in these otherwise healthy individuals (e.g., sex, kidney function, vitamin status, coffee consumption), a study of genetics was warranted. In an initial pilot effort, we documented a genetic predisposition to develop ophthalmic changes after long-duration space flight (4). That is, from a limited study of 5 single-nucleotide polymorphisms (SNPs), we found that the G allele for the MTRR A66G SNP was associated with a greater risk of choroidal folds and cotton-wool spots after flight, and the C allele for SHMT1 C1420T was protective against optic disc edema (4). These data provide a potential pathway for understanding why some individuals develop SANS, while others do not. The initial pilot study of 5 SNPs yielded striking findings, but the 1C pathway is far more complex. An effort was undertaken to examine more than 500 1C SNPs to see if a broader examination could help illuminate this association. That work is ongoing. The astronaut findings led us to advocate for the inclusion of 1C pathway genetic and biochemistry testing on other SANS-related projects, noting that genetics might help identify responders, non-responders, or outliers. The first such effort yielded evidence of an association of specific forms of the MTRR and SHMT-1 SNPs and vitamin B12 status with end-tidal CO2 after acute carbon dioxide exposure (5). The second such effort led to the identification that individuals exposed to strict head-down tilt and CO2 for 30-d who developed optic disc edema also had risk alleles for the two SNPs described above (6). Additionally, we identified a clinical population with many characteristics either attributed or purported to be involved in the ocular changes seen in affected astronauts: women with polycystic ovary syndrome (PCOS). PCOS is a condition of androgen excess and anovulatory menstrual cycles. The shared characteristics and clinical findings between SANS and PCOS generally include higher circulating homocysteine concentrations, increased retinal nerve fiber layer thickness, increased androgen concentrations (or responses), and altered carbohydrate metabolism. To our knowledge, no study has examined whether women with PCOS have asymptomatic ophthalmic anomalies observed in astronauts with SANS. While researchers have evaluated the one-carbon metabolism pathway polymorphisms of PCOS patients, and initial studies show an association with certain one-carbon polymorphisms, none have looked at the set of SNPs identified in our studies that are associated with ophthalmic changes in astronauts. Accordingly, we designed a study to evaluate the association of one-carbon pathway SNPs and ophthalmic findings in patients with PCOS and/or IIH compared to controls. Subjects provided blood samples for vitamin and one carbon biochemistry analyses, an extensive analysis of >500 SNPs associated with one carbon metabolism and had eye examinations and ocular imaging. Data analysis are underway. The data collected to date have shown associations between one carbon pathway biochemistry and genetics and incidence of SANS. The mechanisms for SANS has yet to be identified, although many hypotheses exist. Based on our data, we have developed (8, 9) and expanded (6) a multi-hit hypothesis for how these seemingly disparate findings could be linked. While intriguing, the hypothesis represents the starting point for further research. We aim to clarify the relationship between B-vitamin status and genetics with regard to the risk of SANS. Ultimately, understanding the mechanism(s) behind this will provide a means to predict, prevent, or treat these ophthalmologic pathologies in astronauts, and terrestrial populations.

S M Smith↗
NASA NTRS1982

Increased gluconeogenesis in hyper-G stressed rats

The role of gluconeogenesis in the altered carbohydrate metabolism in rats exposed to hyper-G stress is investigated. The blood levels of the substrates and hormones involved in gluconeogenesis were determined in rats exposed to 3.1 G for various time periods (0.25 to 24 hr). It is found that hyper-G stressed rats showed an immediate increase in plasma glucose at the onset of centrifugation which persisted throughout all the exposure periods. A substantial part of the initial rise in blood glucose is attributed to an increased rate of gluconeogenesis. An increase in liver glycogen deposition was observed in centrifuged rats as early as 0.50 hr exposure time, with progressively larger amounts accumulated as the exposure time was extended to 24 hr. It is concluded that the increase in gluconeogenic activity of hyper-G stressed rats is due to an increase in the mobilization of gluconeogenic substrates from perpheral tissues to the liver as a result of increases in circulating catecholamines and glucagon.

Daligcon, B. C.↗
NASA NTRS1986

Animal studies on Spacelab-3

The flight of two squirrel monkeys and 24 rates on Spacelab-3 was the first mission to provide hand-on maintenance on animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity-dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space-adaptation syndrome. Among the wide variety of parameters measured in the rats, most notable was the dramatic loss of muscle mass and increased fragility of long bones. Other interesting rat findings were those of suppressed interferon production by spleen cells, defective release of growth hormone by somatotrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythopoietin. These results portend a strong role for animals in identifying and elucidating the physiological and anatomical responses of mammals to microgravity.

Schatte, C.↗
NASA NTRS1986

Animal studies on Spacelab-3

Two squirrel monkeys and 24 rats were flown on Spacelab-3 to provide hands-on maintenance of animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity-dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space-adaptation syndrome. Among parameters measured in the rats, most notable is the dramatic loss of muscle mass and increased fragility of long bones. Other rat findings include suppressed interferon production by spleen cells, defective release of growth hormone by somatrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythropoietin.

Schatte, C.↗
NASA NTRS1987

Animal studies on Spacelab-3

The flight of two squirrel monkeys and 24 rats on Spacelab-3 was the first mission to provide hands-on maintenance on animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space adaptation syndrome. Among the wide variety of parameters measured in the rats, most notable was the dramatic loss of muscle mass and increased fragility of long bones. Other interesting rat findings were those of suppressed interferom production by spleen cells, defective release of growth hormone by somatrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythropoietin. These results portend a strong role for animals in identifying and elucidating the physiological and anatomical responses of mammals to microgravity.

Schatte, C.↗
NASA NTRS1995

Immune Alterations in Male and Female Mice after 2-Deoxy-D-Glucose Administration

Administration of 2-deoxy-D-glucose (2-DG), an analog of glucose which inhibits glycolysis by competitive antagonism for phosphohexose isomerase, results in acute periods of intracellular glucoprivation and hyperglycemia resulting in hyperphagia. In addition to these changes in the carbohydrate metabolism, injection of 2-DG results in alterations of both the endocrine and neurological systems as suggested by modifications in oxytocin and glucocorticoid levels and norepinephrine production. Moreover, alterations of the immune response, such as a decrease in the in vitro proliferation of splenocytes after mitogen-stimulation, were observed in mice injected with 2-DG. Sex, genotype and environment are among the factors that may modulate effects of catecholamines and hypothalamo-pituitary-adrenal axis on these immune changes. Sexual dimorphism in immune function resulting from the effects of sex hormones on immune effector cells has been shown in both animals and humans. These observations have important implications, especially with regard to higher incidence of many autoimmune diseases in females. Evidence exists that reproductive hormones influence the immune system and increase the risk of immunologically related disorders in both animals and humans. Indeed, immunological responses in stressful situations may also be confounded by fluctuations of sex hormones especially in females. Lymphocyte distribution, cytoldne production, and the ability of lymphocyte to proliferate in vitro were analyzed in male and female mice to determine if sex influenced 2-DG immunomodulation. In addition, the influence of hormones, especially sex hormones, on these changes were evaluated.

Dreau, Didier↗