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Changes in pituitary growth hormone cells prepared from rats flown on Spacelab 3.

Anterior pituitaries from "small" (250 g) and "large" (400 g) rats flown on the 7-day Spacelab 3 mission were pooled and trypsinized into two single-cell suspensions. Compared with ground-based controls, flight cells appeared to contain more intracellular growth hormone (GH) but release less GH over a 6-day culture period. After implantation into hypophysectomized rats, both sets of flight cells released only 50% of the GH compared with the control cells. Glands from large flight rats contained 44% somatotrophs compared with 37% for controls; small animals showed no difference. There were no striking differences in somatotroph ultrastructure between cells in the four groups. Western blot analysis indicated that there were no major differences in immunoactive GH variants. High-performance liquid chromatography fractionation of culture media indicated that small flight cells released much less of a high-molecular weight variant rich in GH bioactivity. The results suggest that GH cells from rats exposed to microgravity may experience secretory dysfunction. The possibility that this occurs directly at the pituitary cell level is discussed.

Animals↗

Effects of spaceflight on rat pituitary cell function.

The secretory capacity of growth hormone (GH) and prolactin (PRL) cells prepared from rats flown in space on the 12.5-day mission of COSMOS 1887 and the 14-day mission of COSMOS 2044 was evaluated in several postflight tests on Earth. The results showed statistically significant and repeatable decrements in hormone release, especially when biologic (rather than immunologic) assays were used in the tests. Significant and repeatable intracellular changes in GH cells from the flight animals were also found; most important were increases in the GH-specific cytoplasmic staining intensities and cytoplasmic areas occupied by hormone. Tail suspension of rats for 14 days, an established model for mimicking musculoskeletal changes in rats flown in space, resulted in some changes in GH and PRL cell function that were similar to those from animals flown in space. Our results add to a growing body of data that describe deconditioning of physiological systems in spaceflight and provide insights into the time frame that might be required for readaptation of the GH/PRL cell system on return to Earth.

Animals↗

Hormonal modulation of food intake in response to low leptin levels induced by hypergravity.

A loss in fat mass is a common response to centrifugation and it results in low circulating leptin concentrations. However, rats adapted to hypergravity are euphagic. The focus of this study was to examine leptin and other peripheral signals of energy balance in the presence of a hypergravity-induced loss of fat mass and euphagia. Male Sprague-Dawley rats were centrifuged for 14 days at gravity levels of 1.25, 1.5, or 2 G, or they remained stationary at 1 G. Urinary catecholamines, urinary corticosterone, food intake, and body mass were measured on Days 11 to 14. Plasma hormones and epididymal fat pad mass were measured on Day 14. Mean body mass of the 1.25, 1.5, and 2 G groups were significantly (P < 0.05) lower than controls, and no differences were found in food intake (g/day/100 g body mass) between the hypergravity groups and controls. Epididymal fat mass was 14%, 14%, and 21% lower than controls in the 1.25, 1.5, and 2.0 G groups, respectively. Plasma leptin was significantly reduced from controls by 46%, 45%, and 65% in the 1.25, 1.5, and 2 G groups, respectively. Plasma insulin was significantly lower in the 1.25, 1.5, and 2.0 G groups than controls by 35%, 38%, and 33%. No differences were found between controls and hypergravity groups in urinary corticosterone. Mean urinary epinephrine was significantly higher in the 1.5 and 2.0 G groups than in controls. Mean urinary norepinephrine was significantly higher in the 1.25, 1.5 and 2.0 G groups than in controls. Significant correlations were found between G load and body mass, fat mass, leptin, urinary epinephrine, and norepinephrine. During hypergravity exposure, maintenance of food intake is the result of a complex relationship between multiple pathways, which abates the importance of leptin as a primary signal.

Animals↗

Effects of hypergravity exposure on the developing central nervous system: possible involvement of thyroid hormone.

The present study examined the effects of hypergravity exposure on the developing brain and specifically explored the possibility that these effects are mediated by altered thyroid status. Thirty-four timed-pregnant Sprague-Dawley rats were exposed to continuous centrifugation at 1.5 G (HG) from gestational Day 11 until one of three key developmental points: postnatal Day (P) 6, P15, or P21 (10 pups/dam: 5 males/5 females). During the 32-day centrifugation, stationary controls (SC, n = 25 dams) were housed in the same room as HG animals. Neonatal body, forebrain, and cerebellum mass and neonatal and maternal thyroid status were assessed at each time point. The body mass of centrifuged neonates was comparatively lower at each time point. The mass of the forebrain and the mass of the cerebellum were maximally reduced in hypergravity-exposed neonates at P6 by 15.9% and 25.6%, respectively. Analysis of neonatal plasma suggested a transient hypothyroid status, as indicated by increased thyroid stimulating hormone (TSH) level (38.6%) at P6, while maternal plasma TSH levels were maximally elevated at P15 (38.9%). Neither neonatal nor maternal plasma TH levels were altered, suggesting a moderate hypothyroid condition. Thus, continuous exposure of the developing rats to hypergravity during the embryonic and neonatal periods has a highly significant effect on the developing forebrain and cerebellum and neonatal thyroid status (P < 0.05, Bonferroni corrected). These data are consistent with the hypothesized role of the thyroid hormone in mediating the effect of hypergravity in the developing central nervous system and begin to define the role of TH in the overall response of the developing organism to altered gravity.

Animals↗

Leucocytosis, thrombocytosis, and plasma osmolality during rest and exercise: an hypothesis.

The mechanism for inducing leucocytosis (increase in white blood cells) and thrombocytosis (increase in platelets) during exercise is unclear. Because plasma osmolality (Osm) may influence T-cell proliferation, Osm and the number of leucocytes (WBC) and platelets in blood were measured periodically during a 90 min rest period, and were compared with those during upright sitting ergometer exercise in six untrained, healthy men who cycled for 70 min at 71% of their maximal oxygen uptake (VO2max). There were 6 experiments in which the subjects drank different fluid formulations (10 ml x kg(-1) of various ionic and osmotic concentrations intermittently during 60 min of the rest period and during the exercise period. Osmolality, and WBC and platelet counts increased significantly (p < 0.05) within the first 10 min of exercise, but the additional 60 min of exercise did not significantly change the leucocytosis or thrombocytosis. There were low but significant correlations between individual values of total WBC and total Osm during exercise (r0.001(2),284 = 0.39) and during rest plus exercise (r0.001(2),499 = 0.43). With combined data from the six experiments, mean Osm correlated highly and significantly with both mean WBC (r0.001(2),6 = 0.95, p < 0.001) and mean platelets (r0.001(2),6 = 0.94, p < 0.01) during the exercise phase. These data indicate that increases in leucocytes, thrombocytes, and osmolality occur primarily within the first 10 min of high-intensity exercise, but neither hypovolemia nor hyperthermia during exercise contributed to the leucocytosis, thrombocytosis, or hyperosmolality. The high correlations between plasma Osm and WBC or platelet counts suggest changes in osmolality may contribute to the mechanism of leucocytosis and thrombocytosis induced by exercise.

Adult↗

Rat anterior pituitary hormone cells: responses to variable gravity.

BACKGROUND: While life science data dealing with effects of hypogravity are accumulating, relatively little is known about the effects of hypergravity at the level of either the whole animal or the individual cell. The purpose of this experiment was to compare data collected on cells of anterior pituitaries from animals centrifuged at 2G using an experimental design that was identical to that of a spaceflight experiment performed in 1989. HYPOTHESIS: Centrifugation of the animal at 2G for 14 d alters the function and morphology of cells of the anterior pituitary in subsequent in vitro tests at 1G. METHODS: Intact rats were centrifuged at twice Earth's gravity for 14 d in a specially designed animal centrifuge as part of the Cosmos 2G study. This study was designed to replicate a previous spaceflight experiment so that direct comparisons between hyper- (centrifugation, 2G) and hypogravity (spaceflight, 0.001G) could be made. Anterior pituitary cells were then evaluated for cell function and morphology in a variety of post-flight tests. RESULTS: Growth hormone cells from centrifuged animals released less bioactive, but not immunoreactive, growth hormone (GH) than cells from non-centrifuged animals. This was also true for GH released in response to provocative stimulation by a synthetic peptide (growth hormone releasing hormone, GHRH) that causes GH release after binding to cell membrane receptors. Cell morphology was also different between cells from centrifuged and control animals; cells in the experimental group were smaller and less granulated. However, another type of hormone-producing cell contained in these preparations, viz. prolactin cells, was not affected by centrifugation. CONCLUSIONS: Centrifugation of animals for 14 d alters both the in vitro release of GH and GH cell morphology relative to corresponding controls from non-centrifuged animals. Because prolactin cells are not affected by centrifugation, the response is specific to the GH cell.

Animals↗

Association between gravitational force and tissue metabolism in periparturient rats.

Recently, interest in mammalian reproduction and offspring survival in altered gravity has been growing. Because successful lactation is critical for mammalian neonate survival, we have been studying the effect of gravity metabolism. We have shown an exponential relationship between glucose metabolic rate in mammary tissue of periparturient rats and an increase in gravity load. In this study we showed that changes in mammary metabolic rate due to gravity force were accompanied by a decrease in glucose metabolism in adipose tissue and by a reduced size of adipocytes. We assume that these changes are likely due to changes in prolactin or leptin levels related to altered gravity load.

Adipocytes↗

Inhibited interferon production after space flight.

Several studies have been performed in our laboratories indicating that interferon production may be impaired in rodents after space flight. Using an antiorthostatic suspension model that simulates some of the effects of microgravity seen during space flight, we have shown that interferon-alpha/beta production was inhibited. The inhibition was not due solely to the stress of suspension. The inhibited interferon production was transient, as suspended animals returned to normal caging recovered the ability to produce interferon. Antiorthostatic suspension of mice also resulted in a loss of resistance to infection with the diabetogenic strain of encephalomyocarditis virus, which correlated with the drop in interferon production. In rats flown in US Space Shuttle mission SL-3, interferon-gamma production was inhibited severely when spleen cells were challenged with concanavalin-A upon return to earth. In contrast, interleukin-3 production by these cells was normal. These results suggest that immune responses may be altered after antiorthostatic modeling or space flight, and the resistance to viral infections may be especially affected.

Animals↗

Inhibited interferon-gamma but normal interleukin-3 production from rats flown on the space shuttle.

Rats were flown on Space Shuttle SL-3 for 1 week. When spleen cells were removed from these rats and challenged with concanavalin-A, interferon-gamma production was severely inhibited, while interleukin-3 production was unaffected compared to ground-based control rats. These data indicate that there is a defect in interferon-gamma production in rats that have been exposed to spaceflight. This defect could contribute to, and be one reason for, immunosuppression observed after spaceflight.

Animals↗

Controlled Ecological Life Support Systems (CELSS) flight experimentation.

The NASA CELSS program has the goal of developing life support systems for humans in space based on the use of higher plants. The program has supported research at universities with a primary focus of increasing the productivity of candidate crop plants. To understand the effects of the space environment on plant productivity, the CELSS Test Facility (CTF) has been been conceived as an instrument that will permit the evaluation of plant productivity on Space Station Freedom. The CTF will maintain specific environmental conditions and collect data on gas exchange rates and biomass accumulation over the growth period of several crop plants grown sequentially from seed to harvest. The science requirements of the CTF will be described, as will current design concepts and specific technology requirements for operation in micro-gravity.

Crops, Agricultural↗

Quantifying the performance limits of human saccadic targeting during visual search.

In previous studies of saccadic targeting, the issue how visually guided saccades to unambiguous targets are programmed and executed has been examined. These studies have found different degrees of guidance for saccades depending on the task and task difficulty. In this study, we use ideal-observer analysis to estimate the visual information used for the first saccade during a search for a target disk in noise. We quantitatively compare the performance of the first saccadic decision to that of the ideal observer (ie absolute efficiency of the first saccade) and to that of the associated final perceptual decision at the end of the search (ie relative efficiency of the first saccade). Our results show, first, that at all levels of salience tested, the first saccade is based on visual information from the stimulus display, and its highest absolute efficiency is approximately 20%. Second, the efficiency of the first saccade is lower than that of the final perceptual decision after active search (with eye movements) and has a minimum relative efficiency of 19% at the lowest level of saliency investigated. Third, we found that requiring observers to maintain central fixation (no saccades allowed) decreased the absolute efficiency of their perceptual decision by up to a factor of two, but that the magnitude of this effect depended on target salience. Our results demonstrate that ideal-observer analysis can be extended to measure the visual information mediating saccadic target-selection decisions during visual search, which enables direct comparison of saccadic and perceptual efficiencies.

Decision Theory↗

Saccadic and perceptual performance in visual search tasks. I. Contrast detection and discrimination.

Humans use saccadic eye movements when they search for visual targets. We investigated the relationship between the visual processing used by saccades and perception during search by comparing saccadic and perceptual decisions under conditions in which each had access to equal visual information. We measured the accuracy of perceptual judgments and of the first search saccade over a wide range of target saliences [signal-to-noise ratios (SNRs)] in both a contrast-detection and a contrast-discrimination task. We found that saccadic and perceptual performances (1) were similar across SNRs, (2) showed similar task-dependent differences, and (3) were well described by a model based on signal detection theory that explicitly includes observer uncertainty [M. P. Eckstein et al., J. Opt. Soc. Am. A 14, 2406 (1997)1]. Our results demonstrate that the accuracy of the first saccade provides much information about the observer's perceptual state at the time of the saccadic decision and provide evidence that saccades and perception use similar visual processing mechanisms for contrast detection and discrimination.

Adult↗

Saccadic and perceptual performance in visual search tasks. II. Letter discrimination.

Can the oculomotor system use shape cues to guide search saccades? Observers searched for target letters (D, U, or X) among distractors (the letter O in the discrimination task and blank locations in the detection task) in Gaussian white noise. We measured the accuracy of first saccadic responses on each trial and perceptual (i.e., button-press) responses in separate trials with the stimulus duration chosen so that the saccadic and perceptual processing times were matched. We calculated the relative efficiency of saccadic decisions compared with perceptual decisions, eta(rel) = (d'(sac)/d'(per))2. Relative efficiency was low but consistently greater than zero in discrimination tasks (15% +/- 6%) and high in detection tasks (60% +/- 10%). We conclude that the saccadic targeting system can use shape cues, but less efficiently than the perceptual system can.

Adult↗

Cerebrovascular responses during lower body negative pressure-induced presyncope.

BACKGROUND: Reduced orthostatic tolerance is commonly observed after spaceflight, occasionally causing presyncopal symptoms which may be due to low cerebral blood flow (CBF). It has been suggested that CBF decreases in early stages of exposure to orthostatic stress. The purpose of this study was to investigate cerebrovascular responses during presyncope induced by lower body negative pressure (LBNP). HYPOTHESIS: Although CBF decreases during LBNP exposure, blood pressure (BP) or heart rate (HR) contributes more to induce presyncopal conditions. METHODS: Eight healthy male volunteers were exposed to LBNP in steps of 10 mm Hg every 3 min until presyncopal symptoms were detected. Electrocardiogram (ECG) was monitored continuously and arterial BP was measured by arterial tonometry. CBF velocity at the middle cerebral artery was measured by transcranial Doppler sonography (TCD). Cerebral tissue oxygenation was detected using near-infrared spectroscopy (NIRS). We focused our investigation on the data obtained during the final 2 min before the presyncopal endpoint. RESULTS: BP gradually decreased from 2 min to 10 s before the endpoint, and fell more rapidly during the final 10 s. HR did not change significantly during presyncope. CBF velocity did not change significantly, while cerebral tissue oxygenation decreased prior to the presyncopal endpoint in concert with BP. Our results suggest that CBF is maintained in the middle cerebral artery during presyncope, while BP decreases rapidly. CONCLUSIONS: Cerebrovascular hemodynamics are relatively well maintained while arterial hypotension occurs just prior to syncope.

Adult↗

Summary of the key features of seven biomathematical models of human fatigue and performance.

BACKGROUND: Biomathematical models that quantify the effects of circadian and sleep/wake processes on the regulation of alertness and performance have been developed in an effort to predict the magnitude and timing of fatigue-related responses in a variety of contexts (e.g., transmeridian travel, sustained operations, shift work). This paper summarizes key features of seven biomathematical models reviewed as part of the Fatigue and Performance Modeling Workshop held in Seattle, WA, on June 13-14, 2002. The Workshop was jointly sponsored by the National Aeronautics and Space Administration, U.S. Department of Defense, U.S. Army Medical Research and Materiel Command, Office of Naval Research, Air Force Office of Scientific Research, and U.S. Department of Transportation. METHODS: An invitation was sent to developers of seven biomathematical models that were commonly cited in scientific literature and/or supported by government funding. On acceptance of the invitation to attend the Workshop, developers were asked to complete a survey of the goals, capabilities, inputs, and outputs of their biomathematical models of alertness and performance. Data from the completed surveys were summarized and juxtaposed to provide a framework for comparing features of the seven models. RESULTS: Survey responses revealed that models varied greatly relative to their reported goals and capabilities. While all modelers reported that circadian factors were key components of their capabilities, they differed markedly with regard to the roles of sleep and work times as input factors for prediction: four of the seven models had work time as their sole input variable(s), while the other three models relied on various aspects of sleep timing for model input. Models also differed relative to outputs: five sought to predict results from laboratory experiments, field, and operational data, while two models were developed without regard to predicting laboratory experimental results. All modelers provided published papers describing their models, with three of the models being proprietary. CONCLUSIONS: Although all models appear to have been fundamentally influenced by the two-process model of sleep regulation by Borbély, there is considerable diversity among them in the number and type of input and output variables, and their stated goals and capabilities.

Aircraft↗

Spaceflight suppresses exercise-induced release of bioassayable growth hormone.

We have reported that bed rest suppressed the release of bioassayable growth hormone (BGH) that normally occurs after an acute bout of unilateral plantar flexor exercise (G. E. McCall, C. Goulet, R. E. Grindeland, J. A. Hodgson, A. J. Bigbee, and V. R. Edgerton. J. Appl. Physiol. 83: 2086-2090, 1997). In the present study, the effects of spaceflight on the hormonal responses to this exercise protocol were examined. Four male astronauts on the National Aeronautics and Space Administration Shuttle Transport System (STS-78) mission completed the exercise protocol before, during, and after a 17-day spaceflight. The maximal voluntary contraction torque output at the onset of exercise was similar on all test days. Before spaceflight, plasma BGH increased 114-168% from pre- to postexercise. During spaceflight and after 2 days recovery at normal gravity (1 G), the BGH response to exercise was absent. After 4 days of recovery, this response was restored. Plasma concentrations of immunoassayable growth hormone were similar at all time points. The preexercise plasma immunoassayable insulin-like growth factor I (IGF-I) levels were elevated after 12 or 13 days of microgravity, and a approximately 7% postexercise IGF-I increase was independent of this spaceflight effect. The suppression of the BGH response to exercise during spaceflight indicates that some minimum level of chronic neuromuscular activity and/or loading is necessary to maintain a normal exercise-induced BGH release. Moreover, these results suggest that there is a muscle afferent-pituitary axis that can modulate BGH release.

Adult↗

Effects of 17 days of head-down bed rest on hydro-electrolytic regulation in men.

Prolonged periods of head-down bed rest (HDBR) are commonly used to mimic the effects of microgravity. HDBR has been shown to produce, as in space, a cephalad redistribution of circulating blood volume with an increase in central blood volume which induces the early adaptations in blood volume regulating hormones. Changes in atrial natriuretic peptide (ANP), arginine vasopressin (AVP), renin activity and aldosterone have been observed. Many reports describe these endocrine adaptations but few investigations of rhythms are in the literature. We proposed to evaluate the circadian rhythms of the hormones and electrolytes involved in the hydro-electrolytic regulation during a HDBR study which was designed to simulate a 17-day spaceflight (Life and Microgravity Spacelab experiment, LMS, NASA).

Adult↗