Catecholamines and their enzymes in discrete brain areas of rats after space flight on biosatellites Cosmos

The activity of the catecholaminergic system was measured in the hypothalamus of rats which had experienced an 18.5-19.5-day-long stay in the state of weightlessness during space flights on board Soviet biosatellites of the type Cosmos. In the first two experiments, Cosmos 782 and 936, the concentration of norepinephrine and the activities of synthesizing enzymes tyrosine hydroxylase and dopamine-beta-hydroxylase and of the degrading enzyme monoamine oxidase were measured in the total hypothalamus. None of the given parameters was changed after space flight. In the light of the changes of these parameters recorded after exposure to acute stress on Earth, this finding indicates that long-term state of weightlessness does not represent an intensive stressogenic stimulus for the system studied. In the space experiment Cosmos 1129, the concentration of norepinephrine, epinephrine, and dopamine was studied in isolated nuclei of the hypothalamus of rats within 6-10 hr following return from space. Norepinephrine was found to be significantly reduced in the arcuate nucleus, median eminence and periventricular nucleus, epinephrine in the median eminence, periventricular and suprachiasmatic nuclei, whereas dopamine was not significantly changed after space flight. The decreased catecholamine levels found in some hypothalamic nuclei of rats which had undergone space flight indicate that no chronic intensive stressor could have acted during the flight, otherwise the catecholamine concentration would have been increased in the nuclei. The decreased levels must have been induced by the effect of a stressogenic factor acting for a short time only, and that either during the landing maneuver or immediately after landing. Thus long-term exposure of the organism to the state of weightlessness does not represent a stressogenic stimulus for the catecholaminergic system in the hypothalamus, which is one of the regulators of the activation of neuroendocrine reactions under stress.     

Serotonin in individual hypothalamic nuclei of rats after space flight on biosatellite Cosmos 1129.

The experiment on Cosmos 1129 was based on our results obtained in rats exposed to single or repeated restrain stress in the laboratory. These results have convincingly demonstrated a significant increase of serotonin concentration (5-HT) in the hypothalamus in acutely stressed rats. This response, which was found also in the isolated hypothalamic nuclei, was diminished in repeatedly (40 times) immobilized rats. While the concentration of 5-HT was unchanged in the majority of the hypothalamic nuclei of animals subjected to cosmic flight, an increase was recorded only in the supraoptic nucleus (NSO) and a decrease in the periventricular nucleus. These findings demonstrate that only few areas of the hypothalamus respond to cosmic flight with changes of 5-HT concentration and suggest either that long-term cosmic flight cannot be an intensive stressor or that during the flight the rats became already adapted to its long-term effect. However, the exposure of flight rats to repeated immobilization stress resulted in a significant increase of 5-HT in the NSO, para-ventricular and dorsomedial (NDM) nuclei. It should be noted that we have never seen any changes of 5-HT concentration, tryptophan hydroxylase and monoamineoxidase activities in repeatedly (40 times) immobilized rats. On the other hand, the increase of 5-HT concentration in the NDM is a typical finding after seven exposures of rats to immobilization on Earth, daily for 150 min. In the experiment COSMOS 1129 such an increase of 5-HT concentration in the NDM was found not only in the flight group but also in the control group of rats subjected to five daily exposures of immobilization stress. With respect to these findings, the increased 5-HT concentrations observed in some isolated hypothalamic nuclei in the flight group of rats exposed after landing to repeated immobilization stress suggest that long-term space flight and the state of weightlessness do not represent a stressogenic factor with respect to the serotoninergic system in the hypothalamus.     

Effects of microgravity and hypergravity on the cell: investigations on Paramecium tetraurelia.

Previous space CYTOS experiments have shown that space flights resulted in an increase in growth of Paramecia cultures. Microgravity is the major factor responsible of this response: indeed the stimulatory effect disappeared in inflight cultures placed on a 1 g centrifuge aboard the Spacelab. On the other hand, exposure to different levels of hypergravity on Earth resulted in an opposite response, i.e. to a reduced cell growth rate. A possible mechanism of microgravity on paramecia is discussed.     

Changes in chromatin and nucleic acids in rat tissues after two-week spaceflight

The quantitative changes in nucleic acids and chromatin breakdown were followed in blood, thymus and spleen in rats after 14 day flights on board the biosatellites Cosmos-1887 and Cosmos-2044. Quantitative nucleic acid changes within 8-11 h after landing were only mild, most statistically non-significant. An analysis at 48 h after landing showed a marked decrease in a total content of DNA and RNA in spleen and thymus. Within 8-11 h after landing, the symptoms of chromatin breakdown were found as is seen in an increased concentration of its fragments-polydeoxyribonucleotides. The obtained results show that a partial adaptation to microgravity occurs up to flight day 14 in lymphoid organs. Adaptation is accompanied with a reappearing of the sensitive cells. Their chromatin breaks down, then, in a final phase of flight due to hypergravity stress manifesting itself by a temporary increase in polydeoxyribonucleotide concentration several hours after landing. The results are discussed in relation to the changes in chosen parameters after shorter or more prolonged flights.     

On the influence of altered gravity on the growth of fish inner ear otoliths

Inner ear stones (otoliths) of developing cichlid fish (Oreochromis mossambicus) were marked with the calcium tracer alizarin-complexone (AC) at 1g-earth gravity before and after a long-term (20 days) stay of the animals at moderate hypergravity conditions (3g; centrifuge). AC deposition at the otoliths resulted in two fluorescence bands, which enclosed the area grown during exposure to altered gravity. This area was measured with regard to size and asymmetry (size difference between the left and the right stones).

Both utricular and saccular otoliths (lapilli and sagittae, respectively) were significantly smaller after hyper-g exposure as compared to parallely raised 1g-control specimens. The asymmetry concerning the lapilli was pronouncedly decreased in comparison to the 1g-controls. These findings suggest, that the growth and the development of bilateral asymmetry of otoliths is guided by the environmental gravity vector.

Some of the hyper-g animals revealed a kinetotic behaviour at the transfer from hyper-g to normal 1g-earth gravity conditions, which was qualitatively similar to the behaviour observed in previous experiments at the transfer from 1g to microgravity in the course of parabolic aircraft flights. The lapillar asymmetry of kinetotic samples was found to be significantly higher than that of normally behaving experimental specimens. This result supports an earlier theoretical concept, according to which human static space sickness might be based on asymmetric utricular otoliths.     

The asymmetrical growth of otoliths in fish is affected by hypergravity.

Size and asymmetry (size difference between the left and the right side) of inner ear otoliths of larval cichlid fish were determined after a long-term stay at moderate hypergravity conditions (3g; centrifuge), in the course of which the animals completed their ontogenetic development from hatch to freely swimming. Both the normal morphogenetic development as well as the timely onset and gain of performance of the swimming behaviour was not impaired by the experimental conditions. However, both utricular and saccular otoliths (lapilli and sagittae, respectively) were significantly smaller after hyper-g exposure as compared to parallely raised 1g control specimens. The asymmetry of sagittae was significantly increased in the experimental animals, whereas the respective asymmetry con-cerning lapilli was pronouncedly decreased in comparison to the 1g controls. These findings suggest, that the growth and the development of bilateral asymmetry of otoliths is guided by the environmental gravity vector.     

Comparison of gradual and rapid onset runs in a short-arm centrifugation

A gradual onset run (GOR) in a short-arm centrifugation was performed on ten healthy students. The centrifuge had a 1.8 m radius, and the subjects sat on a chair in a cabin. The Gz force increased to 2.2 Gz at 0.1 °/sec² for 32 min. and the same Gz-level was maintained for 20 min. Three out of ten subjects completed the whole protocol; the load on the others was terminated because of symptoms or increased heart rate. There were few symptoms such as vertigo, that was a common problem with a rapid onset run (ROR) in former experiments, due to the short-arm centrifugation. The changes of the flicker test after the load were much less in the GOR protocol than in the ROR protocol, even in the terminated group. GOR seemed preferable to ROR in preventing vertigo even though it took longer to reach the necessary G load.     

Effects of unilateral selective hypergravity stimulation on gait

The purpose of this work is to analyse the neural mechanisms of human motor perturbations induced by dynamic changes in gravity. A unilateral selective hypergravity stimulation (USHS) was produced by stretching an elastic band between the right shoulder and foot. The consequences of the extensor muscle tone change due to the positioning (increased muscular loading) and to its removal (decreased muscular loading) by the elastic band were observed on motor gait skill. Gait spatio-temporal parameters (horizontal displacement of both feet) and lower limb functional length variations (efficiency of flexion and extension movements of the lower limbs) were measured. The latter measure was performed using a device specially designed for that purpose. The main results were: (1) during and after USHS, gait perturbations appeared on the left--the body side not directly stimulated, (2) just after the end of USHS, perturbations were present on the right (homolateral) side evidencing a post treatment effect which caused a decrease in functional shortening of the lower limb during extension and an increase of functional shortening of the lower limb during stance (opposite in sense to the modification observed during swing). Such results afford evidence that, in addition to vestibular receptors, the mechanoreceptors of extensor muscles are involved in determining the changes in motor skills observed at the beginning and at the end of space flights.     

Efficacy of periodic centrifugation of primates during 4-week head-down tilt.

Creation of artificial force of gravity (AFG) to counteract the negative consequences of microgravity in manned space missions of extended duration is one of the high-priority problems of space biology and medicine. However, there are a number of especial effects of AFG (namely, structural changes in muscles and bones, and some other system) which need implantation of electrodes and sensors and are possible only with animals. That is why it is of particular interest to make studies with monkeys whose reactions to changed gravity bear much resemblance with human. The purpose of the investigation was development of a protocol of periodic gravity loads as a counter-measure against the hypokinetic syndrome in Macaca mulatta. Two series of experiments were performed. In the series, animals were split into two groups of 6 species each who were motor restrained with the head end tilted downward at 5 degrees (HDT) for 28 days. Monkeys of group-2 were periodically subjected to centrifugation (HDT+G). During the first series of experiments rotation was conducted in the +Gz direction at g-loads from 1.2 to 1.6 units for 30-40 minutes 4-5 times a week. In the second series, g-load was equal to 1.2 units and the animals were rotated 30 min. 2-3 time a week. The criterion of Y-training protocol efficacy was a test +Gz run at 3 units for 30 s. during which functioning of the cardiovascular systems and its controls was evaluated. The test run was performed prior to and after HDT. Following HDT the animals of group HDT+G were more resistant to the test than their counterparts who had not been trained on the centrifuge. Data of the investigation imply that following HDT and HDT+G alike reduced the amount of total bodily fluids (by approximately 5%), the intracellular component (approximately 4%), and plasma volume (by 6-7%). Yet, there are radical differences between the groups in the levels of reduction in extracellular fluids (by 11% and 6.5%, respectively, P<0.05) and the interstitial component (by 11.5% and 6.5, respectively, P<0.05). Prophylactic centrifugation during HDT was also positive to the muscular blood flow in lower extremities.     

Learning Spatial Localization: From Rat Studies to Computational Models of the Hippocampus

In his landmark article, Richard Morris (1981) introduced a set of rat experiments intended “to demonstrate that rats can rapidly learn to locate an object that they can never see, hear, or smell provided it remains in a fixed spatial location relative to distal room cues” (p. 239). These experimental studies have greatly impacted our understanding of rat spatial cognition. In this article, we address a spatial cognition model primarily based on hippocampus place cell computation where we extend the prior Barrera–Weitzenfeld model (2008) intended to allow navigation in mazes containing corridors. The current work extends beyond the limitations of corridors to enable navigation in open arenas where a rat may move in any direction at any time. The extended work reproduces Morris's rat experiments through virtual rats that search for a hidden platform using visual cues in a circular open maze analogous to the Morris water maze experiments. We show results with virtual rats comparing them to Morris's original studies with rats.     

The effects of extreme nutritional conditions on the neurochemistry of reward and addiction.

Weight loss is a frequent problem in space flights. We now claim that it may affect performance and drug-seeking behavior by altering midbrain neurochemistry. In food-deprived rats (20-30% underweight) basal extracellular dopamine levels in the nucleus accumbens decrease to 40-50% of normal and locomotion is depressed. However, amphetamine-induced dopamine release and locomotion are higher than in controls (1825% vs. 595% after a 25 micromoles d-amphetamine intraaccumbens infusion). The lower basal and the higher stimulated dopamine levels suggest that the neurotransmitter accumulates presynaptically in the accumbens of the underweight rats due to subnormal basal release. Psychostimulants are more rewarding for underweight subjects possibly because they release significantly more dopamine from elevated presynaptic stores into the accumbens. Consequently, weight loss can lead both to depression of performance and propensity to substance abuse. These effects should be considered when providing nutritional resources for space flights so that weight loss is limited.     

Effect of fluid and salt supplements in preventing the development of "osteopenia" in hypokinetic rats

It has been suggested that a daily intake of fluid and salt supplements may be used to prevent bone demineralization in human subjects after prolonged exposure to hypokinesia (diminished muscular activity). Thus, the objective of this investigation was to evaluate the effect of fluid and salt supplementation in the prevention of development of osteoporosis in 64 Wistar rats with an initial body weight of 339-345 g, after exposure to 90 days of hypokinesia. They divided into 4 equal groups: the first group of rats placed under ordinary vivarium conditions and served as vivarium control; the second group were also placed under ordinary vivarium conditions but received daily fluid and salt supplements; the third group were subjected to pure hypokinesia, i.e. without the use of any preventive measures; and the fourth group were submitted to hypokinesia and received daily fluid and salt supplements. For the simulation of the hypokinetic effect the experimental group of rats were kept in small, individual, wooden cages. Through the experimental period the second and fourth group of rats received 8 ml/100 g body wt water and 5 ml 100 g body wt NaCl daily. By the end of the experimental period the animals were decapitated and the spongy matter of tibia and vertebrae of the rats were examined for changes referable to osteoporosis. It was found that the daily intake of fluid and salt supplements caused an increase in the volume density of primary spongiosa of bones. It was concluded that a daily intake of fluid and salt supplements may be used to prevent the development of osteoporosis in rats subjected to prolonged motor activity restriction.     

Metabolic changes in the animals subjected to space flight

The activity of the enzymes involved in aminoacid metabolism (tyrosine aminotransferase, TAT, tryptophan pyrrolase TP, serine dehydratase, SD) with rapid response to glucocorticoids and enzymes requiring for activity increase repeated administration of corticosterone (alanine aminotransferase, ALT, aspartate aminotransferase, AST) in liver, the changes of lipolysis in adipose tissue and the plasma corticosterone levels were studied in rats subjected to space flight (F), in animals from synchron model experiments (SM, simulated conditions of space flight in laboratory) and in intact controls (C). The increase of plasma corticosterone concentration and of the activity of rapidly (TAT, TP, SD) and slowly activating enzymes (ALT, AST) was found in F group 6-10 hr after space flight (18.5 days on biosatellite COSMOS 1129). This suggested the presence of acute-stress (associated primarily with the landing) and chronic stress induced hypercorticosteronemia during the flight. After the short 6-day period of recovery the plasma corticosterone concentrations and the activities of liver enzymes returned to control levels. The exposition of animals to repeated immobilization stress showed higher response of corticosterone levels in flight rats as compared to intact controls. No changes in basal lipolysis were observed in flight rats in comparison to intact controls, however the stimulation of lipolysis by norepinephrine was lower in animals from F and SM groups. This lower response of lipolytic processes to norepinephrine was found in flight animals also after six days period of recovery. These results showed that there are important changes in the regulation of lipolytic processes in adipose tissue of rats after space flight and in the conditions of model experiments.     

Changes in organ perfusion and weight ratios in post-simulated microgravity recovery

Head-down tilt models have been used as ground-based simulations of microgravity. Our previous animal research has demonstrated that there are significant changes in fluid distribution within 2 h after placement in a 45 degrees head-down tilt (45HDT) position and these changes in fluid distribution were still present after 14 days of 45HDT. Consequently, we investigated changes in fluid distribution during recovery from 16 days of 45HDT. Changes in radioactive tracer distribution and organ/body weight ratio were examined in rats randomly assigned to a 45HDT or prone control group. The 45HDT rats were suspended for 16 days and then allowed to recover at the prone position 0, 77, 101, or 125 h post-suspension. Animals were injected with technetium-labeled diethylenetriamine pentaacetate (99mTcDTPA, MW=492 amu, physical half-life of 6.02 h) and then killed 30 min post-injection. Lungs, heart, liver, spleen, kidneys, and brain were harvested, weighed, and measured for radioactive counts. Statistical analyses included two-way analysis of variance (ANOVA) that compared 45HDT versus controls at the four experimental time points. The organ weight divided by the body weight ratio for the brain, heart, kidneys and liver in the 45HDT rats was significantly different than the control rats, regardless of time (treatment). There was no difference between the different time points (time). The average 99mTcDTPA count divided by the organ weight ratio values for the heart, liver, and spleen were significantly higher in the 45HDT group than the control group. The average counts for the heart and spleen were significantly higher at 77, 101, and 125 h than at time zero. We conclude that the major organs have different recovery patterns after 45HDT for 16 days in the rat.     

Chronic orthostatic and antiorthostatic restraint induce neuroendocrine, immune and neurophysiologial disorders in rats

The tail-cast suspension rat model has been developed in ground laboratories interested in space physiology for extensive study of mechanisms causing the pathophysiological syndrome associated with space flights. We used individually-caged male rats to explore the effects of acute and chronic (7d) orthostatic restraint (OR) and head-down anti-orthostatic restraint (AOR) on a series of physiological variables. The acute restraint study showed that (1) the installation of the OR device induced an acute reaction for 2 days, with a substantial rise in ACTH (x2) and CORT (x6), and that (2) the head-down tilt from OR to AOR induced (i) within 10 min and lasting 60 min a 2-fold rise in the intra-cerebro-ventricular pressure (Picv) monitored with an icv telemetric recording system, which receded to normal between 60 and 120 min; and (ii) within 30 min a short-lived 4-fold rise in plasma ACTH and CORT levels. Chronic OR induced (1) the suppression of the diurnal ACTH/CORT rhythm, with increased mean levels, especially for ACTH, (2) a degraded circadian locomotor activity rhythm manifested by a significant reduction in the spectral power of the 24h periodicity and a concomitant emergence of shorter (ultradian) periodicities, (3) an associated, but less pronounced alteration of the diurnal rhythm in body temperature; and (4) a marked increase in baseline plasma levels of IL-1β and an increased reactivity in cytokine release following an E. coli endotoxin (LPS) challenge. AOR induced (1) a similar obliteration of the circadian ACTH/CORT rhythm, (2) the loss of close correlation between ACTH and CORT, (3) a generalized increase in baseline plasma IL-1β levels and (4) more extensive degradation of the arcadian periodicity for both locomotor activity and, to a lesser extent, body temperature, replaced by dominant spectral powers for ultradian periodicities (3 to 10h). In conclusion, both experimental paradigms — but AOR more than OR — caused a blockade of the arcadian rhythmicity of major physiological variables, the loss of normal correlations between ACTH and CORT, and inflammatory-immune hyperreactivity. These pathophysiological disorders may all be parts of a complex chronic stress syndrome.     

The relative role of visual and non-visual cues in determining the perceived direction of "up": experiments in parabolic flight

In order to measure the perceived direction of "up", subjects judged the three-dimensional shape of disks shaded to be compatible with illumination from particular directions. By finding which shaded disk appeared most convex, we were able to infer the perceived direction of illumination. This provides an indirect measure of the subject's perception of the direction of "up". The different cues contributing to this percept were separated by varying the orientation of the subject and the orientation of the visual background relative to gravity. We also measured the effect of decreasing or increasing gravity by making these shape judgements throughout all the phases of parabolic flight (0 g, 2 g and 1 g during level flight). The perceived up direction was modeled by a simple vector sum of "up" defined by vision, the body and gravity. In this model, the weighting of the visual cue became negligible under microgravity and hypergravity conditions.     

高能电子辐照引起的纳米器件翻转效应研究

随着电子器件特征尺寸的减小,其翻转阈值也在降低,使得空间中的高能电子或可诱发纳米器件产生翻转效应。文章选用28 nm的V7型FPGA作为研究对象,分别采用能量为0.2 MeV和1.5 MeV、注量率为5×108～1×109/(cm2·s)的电子进行辐照,结果表明试件产生了明显的翻转效应。结合高能电子作用28 nm器件的仿真结果,经分析可知,1.5 MeV能量的单个电子与器件碰撞不能发生核反应;针对高能电子诱发器件存储单元翻转的几种可能机理,初步认为该器件的翻转是由多个电子同时作用到其中形成局部电荷累积导致的。因此可见,对于电子能量高、通量大的木星等星体的辐射带环境,需考虑高能电子诱发纳米器件翻转对航天器的影响。     

Effect of physical fitness and training on physiological responses to hypogravity.

The studies on the orthostatic tolerance during the hypodynamics exposure seem to be significant in connection with the selection, training and health maintenance of astronauts. Using male human subjects of various physical fitness levels, fluctuations of their physical fitness through 2 weeks of vigorous athletic training were measured in many parameters. For some of the subjects, the effects of 6 hr thermal neutral water immersion exposure in head out supine position on the physical fitness parameters and orthostatic tolerability were compared before training with after training. The results obtained were as follows: (1) Before training, orthostatic tolerability before hypodynamics exposure increased, following the physical fitness levels; the value after the hypodynamics exposure decreased in all the cases, but no differences were observed between the physical fitness levels. (2) As a result of training an increase of the physical fitness capacity was observed. The increase of orthostatic tolerability before hypodynamics exposure was noticed except for athletes. (3) Before hypodynamics exposure the urinary excretion of noradrenaline on non-athlete subjects increased as the physicsl fitness level increased. The values were decreased by physical training, the more so the better the physical fitness. After hypodynamics exposure the same relation was observed. But for athletes the values remain more stable and the decrease by hypodynamics exposure was not so distinctive. Such decreased reaction to hypodynamic conditions seems to reveal the neuro hormonal mechanism for the detrimental adaptation of athletes to hypodynamics. These results suggest that stable athletes do not always have low orthostatic tolerability, but do not respond well to hypodynamic conditions, at least from the orthostatic point of view. The mechanism seems related to sympathetic nerve activity.     

Drosophila melanogaster (fruit fly) locomotion during a sounding rocket flight

The locomotor activity of young Drosophila melanogaster (fruit fly) was studied during a Nike-Orion sounding rocket flight, which included a short-duration microgravity exposure. An infrared monitoring system was used to determine the activity level, instantaneous velocity, and continuous velocity of 240 (120 male, 120 female) fruit flies. Individual flies were placed in chambers that limit their motion to walking. Chambers were oriented both vertically and horizontally with respect to the rocket's longitudinal axis. Significant changes in Drosophila locomotion patterns were observed throughout the sounding rocket flight, including launch, microgravity exposure, payload re-entry, and after ocean impact. During the microgravity portion of the flight (3.8 min), large increases in all locomotion measurements for both sexes were observed, with some measurements doubling compared to pad (1 G) data. Initial effects of microgravity were probably delayed due to large accelerations from the payload despining immediately before entering microgravity. The results indicate that short-duration microgravity exposure has a large effect on locomotor activity for both males and females, at least for a short period of time. The locomotion increases may explain the increased male aging observed during long-duration exposure to microgravity. Studies focusing on long-duration microgravity exposure are needed to confirm these findings, and the relationship of increased aging and locomotion.