Research on the adaptation of skeletal muscle to hypogravity: past and future directions.

Our current understanding of hypogravity-induced atrophy of skeletal muscles is based primarily on studies comparing pre- and post-flight properties of muscles. Interpretations are necessarily qualified by the assumption that the stress of reentry and readjustment to terrestrial gravity do not alter the parameters being analyzed. The neuromuscular system is highly responsive to changes in functional demands and capable of rapid adaptation, making this assumption questionable. A reexamination of the changes in the connective tissue and synaptic terminals of soleus muscles from rats orbited in biosatellites and sampled postflight indicates that these structural alterations represent adaptative responses of the atrophic muscles to the increased workload of returning to 1 G, rather than hypogravity per se. The atrophy of weightlessness is postulated to result because muscles are both underloaded and used less often. Proper testing of this hypothesis requires quantitation of muscle function by monitoring electromyography, force output and length changes during the flight. Experiments conducted in space laboratories, like those being developed for the Space Shuttle, will avoid the complications of reentry before tissue sampling and allow time course atudies of the rate of development of adaptive changes to zero gravity. Another area of great importance for future studies of muscle atrophy is inflight measurement of plasma levels of hormones and tissue receptor levels. Glucocorticoids, thyroid hormone and insulin exert dramatic regulatory influences on muscle structure. Prevention of neuromuscular atrophy becomes increasingly more important as spaceflights increase in duration. Definition of the atrophic mechanism is essential to developing means of preventing neuromuscular atrophy.     

Effects of rectilinear acceleration, caloric and optokinetic stimulation of human subjects in the Spacelab D-1 mission

A set of vestibular experiments was performed during the course of the German Spacelab D-1 mission from 30 October to 6 November 1985 by a consortium of experimenters from various european countries. Similar to the Spacelab SL-1 mission all of the scientific crew members were theoretically and practically trained for the experiments. Baseline measurements for all tests were collected 113, 86, 44, 30 and 18 days prior to the mission and compared with data taken inflight, on the landing day and the consecutive 7 to 14 days.

The hardware comprised mainly a motordriven accelerating platform, the SPACE SLED, and the vestibular helmet, a multi-purpose instrument in support of a variety of vestibular experiments including air-calorisation of the ears, optokinetic stimulation pattern presentation and optical and nystagmographic recording of eye movements.

Measurements of the threshold for the perception of detection of whole body movement did not reveal any dramatic changes in the 2 measured axes inflight when compared to preflight values. Early postflight values show a significantly elevated threshold for all axes in 3 out of 4 subjects.

The caloric nystagmus, already found during the SL-1 mission, was confirmed on all three tested subjects during the D-1 mission. It's amplitude and in some instances it's direction were influenced by horizontal acceleration on the SLED.

The amplitude of optokinetic nystagmus increased when subjects were allowed to free-float over that seen when subjects were fixed.

Stimulation of the neck receptors by roll movements of the body against the fixated head resulted in illusory object motion to the contralateral side. Torsional movements of the eyes during such neck receptor stimulation was present inflight and postflight, while it had not been observed preflight. Most results point to a reduction of otolithic effects in favour of visual and proprioceptive influences for spatial orientation.     

Influence of long-term altered gravity on the swimming performance of developing cichlid fish: including results from the 2nd German Spacelab Mission D-2.

This study presents qualitative and quantitative data concerning gravity-dependent changes in the swimming behaviour of developing cichlid fish larvae (Oreochromis mossambicus) after a 9 resp. 10 days exposure to increased acceleration (centrifuge experiments), to reduced gravity (fast-rotating clinostat), changed accelerations (parabolic aircraft flights) and to near weightlessness (2nd German Spacelab Mission D-2). Changes of gravity initially cause disturbances of the swimming performance of the fish larvae. With prolonged stay in orbit a step by step normalisation of the swimming behaviour took place in the fish. After return to 1g earth conditions no somersaulting or looping could be detected concerning the fish, but still slow and disorientated movements as compared to controls occurred. The fish larvae adapted to earth gravity within 3-5 days. Fish seem to be in a distinct early developmental stages extreme sensitive and adaptable to altered gravity; However, elder fish either do not react or show compensatory behaviour e.g. escape reactions.     

Long-term effects of microgravity and possible countermeasures.

It is well known that long-term exposure to microgravity causes a number of physiological and biochemical changes in humans; among the most significant are: 1) negative calcium balance resulting in the loss of bone; 2) atrophy of antigravity muscles; 3) fluid shifts and decreased plasma volume; and 4) cardiovascular deconditioning that leads to orthostatic intolerance. It is estimated that a mission to Mars may require up to 300 days in a microgravity environment; in the case of an aborted mission, the astronauts may have to remain in reduced gravity for up to three years. Although the Soviet Union has shown that exercise countermeasures appear to be adequate for exposures of up to one year in space, it is questionable whether astronauts could or should have to maintain such regimes for extremely prolonged missions. Therefore, the NASA Life Sciences Division has initiated a program designed to evaluate a number of methods for providing an artificial gravity environment.     

Crustaceans as a model for microgravity-induced muscle atrophy.

Atrophy of skeletal muscles is a serious problem in a microgravity environment. It is hypothesized that the unloading of postural muscles, which no longer must resist gravity force, causes an accelerated breakdown of contractile proteins, resulting in a reduction in muscle mass and strength. A crustacean model using the land crab, Gecarcinus lateralis, to assess the effects of spaceflight on protein metabolism is presented. The model is compared to a developmentally-regulated atrophy in which a premolt reduction in muscle mass allows the withdrawal of the large claws at molt. The biochemical mechanisms underlying protein breakdown involves both Ca(2+)-dependent and multicatalytic proteolytic enzymes. Crustacean claw muscle can be used to determine the interactions between shortening and unloading at the molecular level.     

The first dedicated Life Sciences mission--Spacelab 4.

Spacelab is a large versatile laboratory carried in the bay of the Shuttle Orbiter. The first Spacelab mission dedicated entirely to Life Sciences is known as Spacelab 4. It is scheduled for launch in late 1985 and will remain aloft for seven days. This payload consists of 25 tentatively selected investigations combined into a comprehensive integrated exploration of the effects of acute weightlessness on living systems. An emphasis is placed on studying physiological changes that have been previously observed in manned space flight. This payload has complementary designs in the human and animal investigations in order to validate animal models of human physiology in weightlessness. The experimental subjects include humans, squirrel monkeys, laboratory rats, several species of plants, and frog eggs. The primary scientific objectives include study of the acute cephalic fluid shift, cardiovascular adaptation to weightlessness, including postflight reductions in orthostatic tolerance and exercise capacity, and changes in vestibular function, including space motion sickness, associated with weightlessness. Secondary scientific objectives include the study of red cell mass reduction, negative nitrogen balance, altered calcium metabolism, suppressed in vitro lymphocyte reactivity, gravitropism and photropism in plants, and fertilization and early development in frog eggs. The rationale behind this payload, the selection process, and details of the individual investigations are presented in this paper.     

Gravitational unloading effects on muscle fiber size, phenotype and myonuclear number.

The effects of gravitational unloading with or without intact neural activity and/or tension development on myosin heavy chain (MHC) composition, cross-sectional area (CSA), number of myonuclei, and myonuclear domain (cytoplasmic volume per myonucleus ratio) in single fibers of both slow and fast muscles of rat hindlimbs are reviewed briefly. The atrophic response to unloading is generally graded as follows: slow extensors > fast extensors > fast flexors. Reduction of CSA is usually greater in the most predominant fiber type of that muscle. The percentage of fibers expressing fast MHC isoforms increases in unloaded slow but not fast muscles. Myonuclear number per mm of fiber length and myonuclear domain is decreased in the fibers of the unloaded predominantly slow soleus muscle, but not in the predominantly fast plantaris. Decreases in myonuclear number and domain, however, are observed in plantaris fibers when tenotomy, denervation, or both are combined with hindlimb unloading. All of these results are consistent with the view that a major factor for fiber atrophy is an inhibition or reduction of loading of the hindlimbs. These data also indicate that predominantly slow muscles are more responsive to unloading than predominantly fast muscles.     

Possible actions of gravity on the cellular machinery.

Since the first flight of the ESA Biorack on the German Spacelab Mission D1 in 1985 evidence has been obtained that biological cells and small unicellular organisms function differently under conditions of microgravity. However, there is still lack of scientific proof that these effects are caused by a direct influence on the cells in the weightlessness condition. The question how normal gravity may play a role in cellular activity is being addressed and the results show that gravity may provide important signals during certain state transitions in the cell. These would be gravity-sensitive windows in the biological process. Also, by amplification mechanisms inside the cell, the cell may assume a state that is typical for normal gravity conditions and would change in microgravity. Experimental tools are discussed that would provide the conditions to obtain evidence for direct action of gravity and for the possible existence of gravity-sensitive windows.     

Neuroplastic reactivity of fish induced by altered gravity conditions: a review of recent results.

A review is being presented concerning behavioural, biochemical, histochemical and electronmicroscopical data on the influence of altered gravitational forces on the swimming performance and on the neuronal differentiation of the brain of cichlid fish larvae and adult swordtail fish that had been exposed to hyper-gravity (3g in laboratory centrifuges), hypo-gravity (>10(-2) g in a fast-rotating clinostat) and to near weightlessness (10(-4) g aboard the Spacelab D-2 mission). After long-term alterations of gravity (and parallel light deprivation), initial disturbances in the swimming behaviour followed by a stepwise regain of normal swimming modes are induced. Parallel, neuroplastic reactivities on different levels of investigation were found, such as adaptive alterations of activities of various enzymes in whole brain as well as in specific neuronal integration centers and an intraneuronal reactivity on ultrastructural level in individual brain parts and in the sensory epithelia of the inner ear. Taken together, these data reveal distinct adaptive neuroplastic reactions of fish to altered gravity conditions.     

Transduction of the gravity stimulus in the root statocyte.

The amyloplasts of root statocytes are considered to be the perceptors of gravity. However, their displacement and the starch they contain are not required for gravisensing. The mechanism of the transduction of gravistimulus remains therefore controversial. It is well known that the amplitude of the stimulus is dependent upon the intensity of the acceleration and the inclination of the root with respect to gravity. This strongly supports the hypothesis that the stimulus results in a mechanical effect (pressure or tension) on a cellular structure. Three cellular components are proposed as possible candidates for the role of transducer: the actin filaments, the endoplasmic reticulum and the plasma membrane with its ion channels. Recent results obtained in the frame of the IML 1 Mission of Spacelab show that the endoplasmic reticulum should rather be responsible for the termination of the stimulus. The contacts of amyloplasts with the distal ER could therefore be involved in the regulation of root growth.     

Effects of gravity on early development.

The development of embryonic and larval stages of the South African Toad Xenopus laevis D, was investigated in hyper-g up to 5 g (centrifuge), in simulated 0 g (fast-rotating clinostat), in alternating low g, hyper-g (parabolic flights) and in microgravity (Spacelab missions D1, D-2). The selected developmental stages are assumed to be very sensitive to environmental stimuli. The results showed that the developmental reaction processes run normal also in environments different to 1 g and that aberrations in behavior and morphology normalize after return to 1 g. Development, differentiation, and morphology of the gravity perceiving parts of the vestibular system (macula-organs) had not been affected by exposure to different g-levels.     

Alterations in glucose and protein metabolism in animals subjected to simulated microgravity.

Reduction of physical activity due to disease or environmental restraints, such as total bed rest or exposure to spaceflight, leads to atrophy of skeletal muscle and is frequently accompanied by alterations in food intake and the concentration of metabolic regulatory hormones such as insulin. Hindlimb suspension of laboratory rats, as a model for microgravity, also shows marked atrophy of gravity dependent muscles along with a reduced gain in body weight. Suspended rats exhibit enhanced sensitivity to insulin-induced glucose uptake when compared with normal control rats and resistance to insulin action when compared with control rats matched similarly for reduced body weight gain. These changes are accompanied by decreased insulin binding and tyrosine kinase activity in soleus but not plantaris muscle, unchanged glucose uptake by perfused hindlimb and decreased sensitivity but not responsiveness to insulin-induced suppression of net proteolysis in hindlimb skeletal muscle. These findings suggest that loss of insulin sensitivity during muscle atrophy is associated with decreased insulin binding and tyrosine kinase activity in atrophied soleus muscle along with decreased sensitivity to the effects of insulin on suppressing net protein breakdown but not on enhancing glucose uptake by perfused hindlimb.     

Development of countermeasures for medical problems encountered in space flight.

By the turn of this century, long-duration space missions, either in low Earth orbit or for got early planetary missions, will become commonplace. From the physiological standpoint, exposure to the weightless environment results in changes in body function, some of which are adaptive in nature and some of which can be life threatening. Important issues such as environmental health, radiation protection, physical deconditioning, and bone and muscle loss are of concern to life scientists and mission designers. Physical conditioning techniques such as exercise are not sufficient to protect future space travellers. A review of past experience with piloted missions has shown that gradual breakdown in bone and muscle tissue, together with fluid losses, despite a vigorous exercise regimen can ultimately lead to increased evidence of renal stones, musculoskeletal injuries, and bone fractures. Biological effects of radiation can, over long periods of time increase the risk of cancer development. Today, a vigorous program of study on the means to provide a complex exercise regimen to the antigravity muscles and skeleton is under study. Additional evaluation of artificial gravity as a mechanism to counteract bone and muscle deconditioning and cardiovascular asthenia is under study. New radiation methods are being developed. This paper will deal with the results of these studies.     

Gravity, cellular membranes and associated processes: an introduction.

The aim of the session "Gravity: Cellular Membranes and Associated Processes" was to bring together scientists from different biological disciplines concentrated on the same scientific question: What are the basic interactions or influences, respectively, of gravity on cellular, molecular level? Presentations were selected dealing with the interaction of gravity with basic physico-chemical processes of membranes, such as changes of the membrane composition of human erythrocytes up to ultrastructural changes in a fungus and other objects after exposure to the conditions of space flight, clinorotation or increased acceleration by means of centrifugation. Taken together the data presented here and in the other session of the symposium on "Life and Gravity", clearly outline that future basic physico-chemical studies, and studies dealing with the molecular basis of the cellular signal-perception and transduction, have to be pressed forward in order to understand signal-responses on cellular level, but also of a whole organism.     

从日地系统L2出发借力月球飞越近地小行星

对于停留在日地系统L2的“嫦娥2号”探测器,其后续飞行方案有多个选项,例如主动撞月或重返月球轨道、返回地球轨道或再入大气、飞往地月系统L1/L2或日地系统L1、进入深空飞越近地小行星(最终,“嫦娥2号”于2012年12月13日成功地实现了对Toutatis小行星的近距离飞越)。探讨上述的飞行方案需要对飞行轨道进行初步设计,总的速度脉冲限制在100 m/s以内并且需要考虑探测器同时受到太阳、地球、月球的引力作用。本研究设计了探测器从日地系统L2出发借力月球实现Toutatis小行星飞越的飞行方案,与直接飞越方案相比,借力月球可以进一步节省探测器的燃料消耗,其等效速度脉冲设计值为58.47 m/s。     

Marangoni convection when the surface tension increases with the temperature in normal and low gravity conditions

Thermocapillary convection has been studied in n-heptanol aqueous solutions whose surface tension is increasing with the temperature.

The fluid was confined in a parallelipipedic enclosure and a thermal gradient was imposed parallel to the free liquid/gas interface. The motions induced by the thermocapillary forces have been studied under low gravity conditions during Texus sounding rocket experiments and during the Spacelab D1 mission.

The combined thermocapillary and buoyancy convection have been extensively studied during ground based experiments.

The influence of the aspect ratio and of the alcohol concentration were investigated. Detailed velocity field was determined at the steady state under normal gravity conditions by Laser Doppler Anemometry (LDA).

The aspect ratio was of 0.3 and the temperatures imposed to the lateral sides of the cell were respectively 45°C and 60°C. With these experimental conditions, two superposed contrarotative cells were observed with rapid motions in the surface from the cold to the hot side. This convective pattern was also observed during the normal and high gravity periods of parabolic flights but during the low gravity period of the parabola the motions stopped everywhere in the fluid even in the surface and reappeared immediatly at the pull out of the parabola.     

Microgravity and musculoskeletal system of mammals.

This review surveys data in the literature and our own findings concerning the effects of weightlessness on bones and muscles of white rats flown on Cosmos biosatellites and Spacelab-3. It has been shown that the magnitude and sign of functional changes in muscles depend on their biomechanical profile. Structural and metabolic foundations of functional adaptation and its dynamics have been identified: in 5-7 day flights muscle contractility changes are mainly associated with a diminished activity of excitation-contraction coupling, in longer-term flights they are produced by changes in myosin populations specific for myofibers of different functional profile. At early flight stages (up to 1 week) osteoporosis and bone demineralization are very mild; therefore decrease in bone mechanical strength may be caused by changes in physico-chemical parameters of the collagen-crystal system. In flights of up to 3 weeks noticeable osteoporosis develops which is primarily produced by osteogenesis inhibition and which is responsible for a marked decrease of bone strength. These changes may result from uncoupling of bone resorption and remodelling processes. This uncoupling is characterized as incomplete osteogenesis and may be caused by changes in the collagen composition of the organic bone matrix. The above-mentioned adaptive changes in muscle functions of specific skeletal compartments may play a role in different responses of various bones to weightlessness.     

Gravitropism of basidiomycetous fungi--on Earth and in microgravity.

In order to achieve perfect positioning of their lamellae for spore dispersal, fruiting bodies of higher fungi rely on the omnipresent force gravity. Only accurate negatively gravitropic orientation of the fruiting body cap will guarantee successful reproduction. A spaceflight experiment during the STS-55 Spacelab mission in 1993 confirmed that the factor gravity is employed for spatial orientation. Most likely every hypha in the transition zone between the stipe and the cap region is capable of sensing gravity. Sensing presumably involves slight sedimentation of nuclei which subsequently causes deformation of the net-like arrangement of F-actin filament strands. Hyphal elongation is probably driven by hormone-controlled activation and redistribution of vesicle traffic and vesicle incorporation into the vacuoles and cell walls to subsequently cause increased water uptake and turgor pressure. Stipe bending is achieved by way of differential growth of the flanks of the upper-most stipe region. After reorientation to a horizontal position, elongation of the upper flank hyphae decreases 40% while elongation of the lower flank slightly increases. On the cellular level gravity-stimulated vesicle accumulation was observed in hyphae of the lower flank.     

Microgravity effects on "postural" muscle activity patterns.

Changes in neuromuscular activation patterns associated with movements made in microgravity can contribute to muscular atrophy. Using EMG to monitor "postural" muscles, it was found that free floating arm flexions made in microgravity were not always preceded by neuromuscular activation patterns normally observed during movements made in unit gravity. Additionally, manipulation of foot sensory input during microgravity arm flexion impacted upon anticipatory postural muscle activation.