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.     

Effect of weightlessness on sympathetic-adrenomedullary activity of rats.

Three cosmic experiments were performed in which rats spent 18-20 days in space on board the biosatellites "COSMOS 782", "COSMOS 936" and "COSMOS 1129". The following indicators of the sympathetic-adrenomedullary system (SAS) activity were measured: tissue and plasma catecholamines (CA), CA-synthesizing enzymes--tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), phenylethanolamine-N-methyltransferase (PNMT)--as well as CA-degrading enzymes-monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). Adrenal epinephrine (EPI) and norepinephrine (NE) as well as CA-synthesizing and degrading enzymes were not significantly changed in the animals after flight on COSMOS 782. On the other hand, a significant increase was found in heart CA, the indicator which is usually decreased after stress. 26 days after landing all values were at control levels. The results obtained, compared to our previous stress experiments on Earth, suggest that prolonged weightlessness does not appear to be a pronounced stressful stimulus for the SAS. Heart and plasma CA, mainly NE, were increased both in the group living in the state of weightlessness and the group living in a centrifuge and exposed to artificial gravitation 1 g (COSMOS 936), suggesting again that prolonged weightlessness is not an intensive stressful stimulus for the SAS. The animals exposed after space flight on COSMOS 1129 to repeated immobilization stress on Earth showed a significant decrease of adrenal EPI and an expressive increase of adrenal TH activity compared to stressed animals which were not in space. Thus, the results corroborate that prolonged state of weightlessness during space flight though not representing by itself an intensive stressful stimulus for the sympathetic-adrenomedullary system, was found to potentiate the response of "cosmic rats" to stress exposure after return to Earth.     

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.     

The effect of hypokinesia on lipid metabolism in adipose tissue

The increase of nonesterified fatty acid (NEFA) concentration in plasma was observed in rats subjected to hypokinesia for 1-60 days. In the period of recovery (7 and 21 days after 60 days immobilization) the content of NEFA returned to control values. The increase of fatty acid release from adipose tissue was observed in hypokinetic rats, however the stimulation of lipolysis by norepinephrine was lower in rats exposed to hypokinesis. The decrease of the binding capacity and a diminished number of beta-adrenergic receptors were found in animals after hypokinesia. The augmentation of the incorporation of glucose into lipids and the marked increase in the stimulation of lipogenesis by insulin were found in adipose tissue of rats subjected to long-term hypokinesia. These results showed an important effect of hypokinesia on lipid mobilization, on lipogenesis and on the processes of hormone regulation in adipose tissue.     

Recent results of the joint ESA-DARA/IBMP experiments Biokosmos "Seeds"

Comparison of experimental data obtained from short (SDEF) and long duration exposure flights (LDEF) have recently led to results which will be significant for longer and/or repeated sojourn of man in space. Under orbital conditions biological stress and damage are induced in test subjects by cosmic radiation, especially the high energetic, densely ionizing component of heavy ions. Plant seeds were successful model systems for a biotest in studying the physiological damages and mutagenic effect caused by ionizing cosmic radiation in particular stem cells. Dosimetrically, the subdivision into charge- and Let-groups reveals the contribution of the intermediate group (LET = 350-1000 MeV/cm) due to the medium heavy ions (Z = 6-10). Their relative contribution increases with the lower inclination of the orbit of LDEF-1; on the other hand, the total fluence becomes higher with longer duration of the flight. The observed endpoints of the biological radiation damage hint at a correlation with particle dose rate rather than with the dose; additionally, data on shielding effects inside and outside the space craft and its exposure were gained from the different SDEF- and LDEF-missions.     

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.     

Respective role of microgravity and cosmic rays on Paramecium tetraurelia cultured aboard Salyut 6.

Paramecium tetraurelia cultured aboard Salyut 6 have shown in increase in cell growth rate, cell volume, water content and changes in electrolyte content. Additional experiments, carried out in balloon flight and on earth, showed that the stimulating effect observed on cell proliferation is related to exposure to cosmic rays. Other changes seem to be due to a direct effect of microgravity on cell. Mechanism of gravity action on cell is discussed.     

Long-term biological investigations in space

Missions in space within the next two decades will be of longer duration than those carried out up to the present time, and the effects of such long-term flights on biological organisms are unknown. Results of biological experiments that have been performed to date cannot be extrapolated to results in future flights because of the unknown influence of adaptation over a long period of time. Prior experiments with Axolotl, fishes, and vertebrates by our research team (in part with sounding rockets) showed that these specimens did not appear to be suitable for long-term missions on which minimization of expense, technique, and energy is required. Subsequent investigations have shown the suitability of the leech (Hirudo medicinalis), which consumes blood of mammals up to ten times its own weight (1 g) and can live more than 2 years without further food supply. Emphasis in the experiments with Hirudo medicinalis is placed on metabolic rhythm and motility. Resorption and diffusion in tissue, development, and growth under long-term effects of cosmic proton radiation and zero-gravity are other focal points. The constancy of cellular life in the mature animals is a point in favor of these specimens. We have also taken into account the synergistic effects of the space environment on the problems just mentioned. The life-support system constructed for the leech has been tested successfully in four sounding rocket flights and, on that basis, has been prepared for a long-term mission. Long-term investigations out of the terrestrial biosphere will provide us with information concerning the degree of adaptation of certain physiological and biochemical functions and as to what extent biological readjustment or repair processes can occur under the specific stress conditions of space flight.     

Study of physiological effects of weightlessness and artificial gravity in the flight of the biosatellite Cosmos-936.

In the 18.5-day flight of the Soviet biosatellite Cosmos-936 (3-22, August 1977) com-parative investigations of the physiological effects of prolonged weightlessness (20 rats) and artificial gravity of 1 g (10 rats) were carried out. Throughout the flight artificial gravity was generated by means of animal rotation in two centrifuges with a radius of 320mm. Postflight examination of animals and treatment of the flight data were performed by Soviet scientists in collaboration with the specialists from Bulgaria, Czechoslovakia, the German Democratic Republic, Hungary, Poland, Rumania, France and the U.S.A. During the flight the total motor activity of the weightless rats was higher and their body temperature was lower than those of the centrifuged animals. Postflight examination of the weightless rats showed a greater percentage of errors during maze an increase in water intake and a decrease in diuresis; a fall of the resistance of peripheral red cells; an increase in the conditionally pathogenic microflora in the mouth; a decrease of oxygen consumption, carbon dioxide production and energy expenditures; a drop in the static physical endurance; a decline in the capacity to keep balance on the rail; an increase in the latent period of the lifting reflex, etc. The centrifugal animals displayed lesser or no change of the above type. These findings together with the biochemical and morphological data give evidence that during and after flight adaptive processes in the centrifuged rats developed better.     

Space radiation concerns for manned exploration.

Spaceflight exposes astronaut crews to natural ionizing radiation. To date, exposures in manned spaceflight have been well below the career limits recommended to NASA by the National Council of Radiation Protection and Measurements (NCRP). This will not be the case for long-duration exploratory class missions. Additionally. International Space Station (ISS) crews will receive higher doses than earlier flight crews. Uncertainties in our understanding of long-term bioeffects, as well as updated analyses of the Hiroshima. Nagasaki and Chernobyl tumorigenesis data, have prompted the NCRP to recommend further reductions by 30-50% for career dose limit guidelines. Intelligent spacecraft design and material selection can provide a shielding strategy capable of maintaining crew exposures within recommended guidelines. Current studies on newer radioprotectant compounds may find combinations of agents which further diminish the risk of radiation-induced bioeffects to the crew.     

Disturbance in the lower ionosphere that accompanied the reentry of the Chelyabinsk cosmic body

The paper describes quasi-periodic and aperiodic variations in the phase and amplitude of radio waves of LF and VLF ranges, which accompanied the flight and explosion of the Chelyabinsk meteoroid. Quasi-periodic variations in the phase have been explained by the generation of acoustic-gravity waves in the atmosphere, which modulate the electron density in the ionosphere and the phase of radio waves. Aperiodic variations in the phase and amplitude of radio waves are associated with an increase in the electron density in the lower ionosphere (at altitudes of 65–70 km). This increase was most likely caused by the interactions of subsystems in the Earth–atmosphere–ionosphere–magnetosphere system or, more correctly, by the precipitation of high-energy electrons from the magnetosphere into the lower ionosphere, which was stimulated by the flight and explosion of a cosmic body. According to the estimates, the density of the flux of electrons with energies of 100 KeV should be on the order of 106 m^–2 s^–1.     

Increased urinary excretion rates of serotonin and metabolites during bedrest

Astronauts are often on a voluntarily reduced energy intake during space missions, possibly caused by a metabolic or emotional stress response with involvement of the central serotonergic system (SES). We investigated 24 h urinary excretion (24 h-E) of serotonin (5-HT) and 5-hydroxyindol acidic acid as indicators of the SES in healthy males under two different normocaloric conditions: normal physical activity (NPA) and -6 degree head-down-tilt (HDT). HDT or NPA were randomly arranged with a recovery period of 6 months in between. 24 h-E of hormones varied widely among individuals. Values were higher in HDT compared to NPA. Assuming that the 24 h-E values are, beside being indicators for alterations in the number and metabolism of platelets. Also indicators of central SES, HDT condition seems to activate central SES in a higher degree compared to NPA. Therefore, changes in central SES might be involved in the mechanisms associated with space flight or microgravity, including possible maladaptations such as voluntary undernutrition.     

On the problem of lunar radiation environment

In connection with projects of manned bases on the Moon it becomes topical to estimate radiation danger for their inhabitants. In this paper we describe a method of evaluation of the radiation environment on the lunar surface produced by galactic and solar cosmic rays. The roles of both primary and secondary radiations generated in the depth of the lunar soil under the action of high-energy protons and nuclei are taken into account. Calculated fluxes of particles are used in order to estimate annual averaged absorbed and equivalent local dose rates in tissues. It is established that in the lunar rock the contribution of secondary neutrons to the dose rate exceeds that of protons. The contribution of the secondary particles generated by nuclei of galactic cosmic rays to the dose rate is estimated.     

Reloading partly recovers bone mineral density and mechanical properties in hind limb unloaded rats

Skeletal unloading results in decreased bone formation and bone mass. During long-term space flight, the decreased bone mass is impossible to fully recover. Therefore, it is necessary to develop the effective countermeasures to prevent spaceflight-induced bone loss. Hindlimb Unloading (HLU) simulates effects of weightlessness and is utilized extensively to examine the response of musculoskeletal systems to certain aspects of space flight. The purpose of this study is to investigate the effects of a 4-week HLU in rats and subsequent reloading on the bone mineral density (BMD) and mechanical properties of load-bearing bones.     

The next steps in exploring deep space—A cosmic study by the IAA

This paper presents the results of an IAA cosmic study on the Next Steps in Exploring Deep Space, the goal of which is to provide a vision for the scientific exploration of space by humans in the first half of the 21st Century. The study provides a roadmap for a systematic, logical, and science-driven plan for exploration of the Solar System and unlocking the mysteries of the Universe—a program that builds gradually and systematically to establish a permanent presence at each outpost along the way, and that builds the communications, transportation and other logistical infrastructure as it proceeds. The study suggests a set of long-term scientific goals for space exploration that provide the context for carrying out scientific investigations at specific destinations in space. An architecture is derived for the space flight infrastructure required to pursue these science goals at the specified destinations, including examination of the relevant policy and public engagement in this enterprise.     

Degradation of cyanobacterial biosignatures by ionizing radiation

Primitive photosynthetic microorganisms, either dormant or dead, may remain today on the martian surface, akin to terrestrial cyanobacteria surviving endolithically in martian analog sites on Earth such as the Antarctic Dry Valleys and the Atacama Desert. Potential markers of martian photoautotrophs include the red edge of chlorophyll reflectance spectra or fluorescence emission from systems of light-harvesting pigments. Such biosignatures, however, would be modified and degraded by long-term exposure to ionizing radiation from the unshielded cosmic ray flux onto the martian surface. In this initial study into this issue, three analytical techniques--absorbance, reflectance, and fluorescence spectroscopy--were employed to determine the progression of the radiolytic destruction of cyanobacteria. The pattern of signal loss for chlorophyll reflection and fluorescence from several biomolecules is characterized and quantified after increasing exposures to ionizing gamma radiation. This allows estimation of the degradation rates of cyanobacterial biosignatures on the martian surface and the identification of promising detectable fluorescent break-down products.     

Skylab experiment M-092: results of the first manned mission

Blood pressure at 30-sec intervals, heart rate, and percentage increase in leg volume continuously were recorded during a 25-min protocol in the M092 Inflight Lower Body Negative Pressure (LBNP) experiment carried out in the first manned Skylab mission. These data were collected during six tests on each crewman over a 5-month preflight period. The protocol consisted of a 5-min resting control period, 1 min at -8, 1 min at -16, 3 min at -30, 5 min at -40, and 5 min at -50 mm Hg LBNP. A 5-min recovery period followed. Inflight tests were performed at approximately 3-day intervals through the 28-day mission. Individual variations in cardiovascular responses to LBNP during the preflight period continued to be demonstrated in the inflight tests. Measurements of the calf indicated that a large volume of fluid was shifted out of the legs early in the flight and that a slower decrease in leg volume, presumably due to loss of muscle tissue, continued throughout the flight. Resting heart rates tended to be low early in the flight and to increase slightly as the flight progressed. Resting blood pressure varied but usually was characterized by slightly elevated systolic blood pressure, lower diastolic pressure, and higher pulse pressures than during preflight examinations. During LBNP inflight a much greater increase in leg volume occurred than in preflight tests. Large increases occurred even at the smallest levels of negative pressure, suggesting that the veins of the legs were relatively empty at the beginning of the LBNP. The greater volume of blood pooled in the legs was associated with greater increases of heart rate and diastolic pressure and larger falls of systolic and pulse pressure than seen in preflight tests. The LBNP protocol represented a greater stress inflight, and on three occasions it was necessary to stop the test early because of impending syncopal reactions. LBNP responses inflight appeared to predict the degree of postflight orthostatic intolerance. Postflight responses to LBNP during the first 48 hours were characterized by marked elevations of heart rate and instability of blood pressure. In addition, systolic and diastolic pressures were typically elevated considerably both at rest and also during stress. The time required for cardiovascular responses to return to preflight levels was much slower than in the case of Apollo crewmen.     

Plasma and urine catecholamine levels in cosmonauts during long-term stay on Space Station Salyut-7.

The activity of the sympathetic adrenal system in cosmonauts exposed to a stay in space lasting for about half a year has so far been studied only by measuring catecholamine levels in plasma and urine samples taken before space flight and after landing. The device "Plasma 01", specially designed for collecting and processing venous blood from subjects during space flight on board the station Salyut-7 rendered it possible for the first time to collect and freeze samples of blood from cosmonauts in the course of a long-term 237-day space flight. A physician-cosmonaut collected samples of blood and urine from two cosmonauts over the period of days 217-219 of their stay in space. The samples were transported to Earth frozen. As indicators of the sympathetic adrenal system activity, plasma and urine concentrations of epinephrine and norepinephrine as well as urine levels of the catecholamine metabolites metanephrine, normetanephrine, and vanillylmandelic acid were determined before, during and after space flight. On days 217-219 of space flight plasma epinephrine and norepinephrine levels were slightly increased, yet not substantially different from normal. During stress situations plasma norepinephrine and epinephrine levels usually exhibit a manifold increase. On days 217-219 of space flight norepinephrine and epinephrine levels in urine were comparable with pre-flight values and the levels of their metabolites were even significantly decreased. All the parameters studied, particularly plasma norepinephrine as well as urine norepinephrine, normetanephrine, and vanillylmandelic acid, reached the highest values 8 days after landing. The results obtained suggest that, in the period of days 217-219 of the cosmonauts stay in space in the state of weightlessness, the sympathetic adrenal system is either not activated at all or there is but a slight activation induced by specific activities of the cosmonauts, whereas in the process of re-adaptation after space flight on Earth this system is considerably more markedly activated.     

深空辐射环境对航天活动的危害及对策

深空辐射环境是影响深空探测任务的一个主要因素,它主要包括太阳粒子事件、银河宇宙射线、俘获辐射带和黑体表面辐射。文章分析了它对航天活动的危害,并探讨了相应的对策。     

Bone effects of space flight: analysis by quantum concept of bone remodelling.

During the manned Skylab flights mineral losses from the calcaneum and changes in external calcium balance were in the ranges found for healthy subjects at bedrest. Calcium balance reached a nadir of -200 mg/day by two months with no change thereafter; the negative balance was due to increased urinary excretion with no change in net absorption. The total calcium loss averaged 18 g in the longest flight of 84 days; the densitiometric data suggested that about two-thirds of this came from trabecular bone and about one-third from cortical bone. These data could represent reversible bone loss due to increased birth rate of normal osteoclasts and osteoblasts and consequent increase in bone turnover and in reversible mineral deficit, or irreversible bone loss due to overactive osteoclasts and/or underactive osteoblasts. If the former explanation is correct, significant bone loss is unlikely whatever the duration of future flights, except in older persons already losing bone; if the latter explanation is correct, space flights longer than six months may lead to a significant increase in fracture risk in later life. Neither terrestrial immobilization nor unwilling animals in orbit are ideal models for the effects of space flight on human bone. To choose between reversible and irreversible mechanisms of bone loss, and to determine the effects of space flight on lifelong fracture risk, future astronauts and cosmonauts must undergo adequate histologic study of bone after in vivo tetracycline labeling.