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Simulated weightlessness to induce chronic hypoactivity of brain norepinephrine for exercise and stress studies.

Although research on the relationship between exercise training and physiological stress reactivity is increasing, we know little about the involvement of brain neurochemistry. Moreover, the few studies that have been performed have concentrated on animals with normally functioning neurochemistry exposed to an acute stressor. Biomedical research is drawing an association between hypoactivation of the physiological stress response and certain medical conditions. As such, there is a need for an animal model that manifests a chronic hypoactivity of the stress system. In this report we describe the results from studies on norepinephrine changes with actual and simulated weightlessness in animals and humans. There is consistent evidence with rats that 14 d of simulated weightlessness produces reduced norepinephrine turnover in selected brainstem nuclei and peripheral tissue mediating the physiological stress response. Little is known about other brain regions, particularly the hypothlamus. These preliminary data suggest that simulated weightlessness is one method by which a chronic hypoactivity of norepinephrine biosynthesis or release might be induced to study exercise training as an intervention.

Adaptation, Physiological↗

Adaptability of Japanese quail chicks to conditions of simulated weightlessness.

The objective of this study was to evaluate the adaptability of young Japanese quail chicks to the simulated weightlessness, represented by hypodynamy. Unsexed hatchlings were subjected to hypodynamy on either the first, second or third day of age and reared under these conditions to 21 days of age. During this period, the control quail chicks were housed in a floor box. The effect of hypodynamy on adaptability of chicks was significant (P < 0.001). Approximately 75% of all chicks exposed to hypodynamy were not able to adapt in three experimental groups, although significant differences in adaptability were not found between these groups. Those birds were considered as non-adapted (eliminated from experiment) that manifested hyperactivity, escape attempts, turning 180 degrees in the sling, soaking in the water from the drinker, as well as the total apathy, at least three times per day. This experiment confirmed that some quail chicks are capable of adapting to conditions simulating weightlessness to 21 days of age and that the first 2-weeks after hatching may be a critical period of quail sensitivity to hypodynamy. This finding raises a key issue relevant to rearing quails in simulated weightlessness until the age of sexual maturity.

Adaptation, Physiological↗

Bone loss during simulated weightlessness: a biomechanical and mineralization study in the rat model.

BACKGROUND: Astronauts exposed to weightlessness for extended periods experience significant decreases in bone mineral density. The clinical implications of this demineralization are not entirely clear, and the biomechanics involved are not completely understood. HYPOTHESIS: Local (rather than global) measurements of geometry and calcium concentration effectively predict femur strength in adult rats exposed to a hind-limb suspension model of weightlessness. METHODS: Female Fischer rats (6-mo-old) were divided into groups of control and hind-limb-suspended animals. Animals were sacrificed after 2 or 4 wk of hind-limb suspension, and both femurs removed from each animal. The 3-point bending strength and total bone mineralization were determined for one femur from each animal, and the mid-shaft cross-sectional geometrical properties and distribution of calcium were determined for the contralateral femur. RESULTS: Although suspension led to significant decreases in total bone mineralization, the concentration of calcium at the anterior periosteal surface was unaffected. Total bone percent mineralization was not well correlated with structural properties, but bone geometrical properties (particularly cross-sectional moment of inertia and length) correlated strongly with ultimate bending strength (r2 = 0.81). Differences in bone geometry due to suspension were consistent with a distribution of bone material closer to the axis of the femur. CONCLUSIONS: Structural properties of bone are predicted well by bone geometry and poorly by total bone percent mineralization. Decreased bone mechanical strength in this model of weightlessness is primarily due to a distribution of bone material nearer the axis of the bone.

Animals↗

Motor reactions and vestibular reflexes in cats and monkey in weightlessness.

Close morpho-functional relationships of the cerebellum and vestibular system at all stages of phylogenesis of vertebrates suggest that cerebellum can be regarded as an important center of gravireceptive function. Direct examination of electrical activity of the labyrinth in cats during transient (1-2 sec) state of weightlessness produced by free fall has shown that there was an almost two fold increase in both the rate and amplitude of electrical activity in the vestibular ganglion. It is commonly accepted at present time that the conditions of orbital flight around Earth closely connect with weightlessness that usually manifests itself as undesirable factor of flight. It is known, that vestibular, proprioceptive, visual and other sensory modalities are converted on the cerebellum, which would indicate that this information is used for motor coordination and spatial orientation. Undoubtedly, origin of many vestibulo-motor disturbances during flight and in postflight period to a considerable degree depends on weightlessness. On the whole the visual illusions, motor discoordination, and space sickness, including vomiting are referred to the "space adaptation syndrome." But nature of these disturbances still is not well understood. This investigation was dedicated to study of vestibular and motor reactions of cats and monkey in short-term microgravity.

Animals↗

The effects of prolonged weightlessness and reduced gravity environments on human survival.

The manned exploration of the solar system and the surfaces of some of the smaller planets and larger satellites requires that we are able to keep the adverse human physiological response to long term exposure to near zero and greatly reduced gravity environments within acceptable limits consistent with metabolic function. This paper examines the physiological changes associated with microgravity conditions with particular reference to the weightless demineralizatoin of bone (WDB). It is suggested that many of these changes are the result of physical/mechanical processes and are not primarily a medical problem. There are thus two immediately obvious and workable, if relatively costly, solutions to the problem of weightlessness. The provision of a near 1 g field during prolonged space flights, and/or the development of rapid transit spacecraft capable of significant acceleration and short flight times. Although these developments could remove or greatly ameliorate the effects of weightlessness during long-distance space flights there remains a problem relating to the long term colonization of the surfaces of Mars, the Moon, and other small solar system bodies. It is not yet known whether or not there is a critical threshold value of 'g' below which viable human physiological function cannot be sustained. If such a threshold exists permanent colonization may only be possible if the threshold value of 'g' is less than that at the surface of the planet on which we wish to settle.

Adaptation, Physiological↗

[Plastic changes of structure, function and perivascular innvervation of arterial vasculature during simulated weightlessness].

At present, whether structural remodeling and functional adjustment of arterial vasculature might occur during weightlessness has not yet been fully recognized. Hence, a serial work using tail-suspension rat model aimed at elucidating the nature, time course and reversibility of changes in structure, function and perivascular innervation of arterial vasculature in different body parts during and after simulated weightlessness was started several years ago in this laboratory. Our results have demonstrated the differentiated effects of simulated weightlessness on arterial vasculature in different body parts: (1) in the hindquarter arteries and arterioles, it leads to atrophic remodeling changes, diminished vasoconstrictor responsiveness and perivascular hypoinnervation; (2) in the fore body part, it leads to hypertrophic changes, enhanced responsiveness and hyperinnervation in the arteries. The results suggest that microgravity-induced changes in cardiovascular effector apparatus, e. g., the structural remodeling and functional adjustment in vascular smooth muscle, might play an important role in the genesis of postflight orthostatic intolerance.

Adaptation, Physiological↗

[Effects of simulated weightlessness on vasoreactivity of hindlimb arterial bed in rats].

OBJECTIVE: To investigate the alterations in vasoreactivity of hindlimb arterial bed after simulated weightlessness. METHOD: The tail-suspended rat model was used to simulate weightlessness, and the alterations in vasoreactivity of arterial bed were examined in vitro using isolated, constant flow perfused hindlimb of 2-wk suspended rats and control rats. RESULT: Perfusion flow-pressure relationship of hindlimb arterial bed showed no significant differences between suspended rats and control rats; but vascular responses to KCl (20-100 mM) and PE(10(-8)-10(-4) M) were decreased in hindlimb arterial bed of suspended rats as compared with that of control rats. CONCLUSION: Contractile ability of resistance vessels was diminished in simulated weightlessness rats, and a compromised ability of resistance vessels to increase peripheral resistance may play an important role in occurrence of orthostatic intolerance.

Adaptation, Physiological↗

[Effect of simulated weightlessness on the apoptosis of thymus cells in tail-suspended mice].

OBJECTIVE: To investigate the effect of simulated weightlessness on apoptosis of thymus cells in mice. METHOD: Tail-suspended mice were used as an animal model of simulated weightlessness; chromosome breakage was measured by PI staining, and changes of cell membrane were determined by Annexin-V analysis. RESULT: As compared with the control, there was no obvious chromosome breakage; the total number of apoptotic cells and number of early apoptotic cells increased in 1 d suspended group; the number of early apoptotic cells increased significantly and the total number of apoptotic cells increased very significantly in 2d suspended groups. CONCLUSION: These results suggested that simulated weightlessness could promote apoptosis of thymus cells.

Animals↗

[Vasoconstrictor responsiveness of rat basilar artery enhanced by simulated weightlessness].

OBJECTIVE: To investigate the effects of simulated weightlessness on contractile responsiveness of the basilar artery. METHODS: Rats were subjected to tail-suspension for 4-wk to simulate the effect of weightlessness, responses of perfused isolated basilar arterial rings to various vasoactive compounds were examined. RESULTS: Maximal isometric contractile responses to KCl [ (10~100) mmol/L], arginine vasopressin [AVP, (10(-15)~10(-7) mol/L], or 5-hydroxytryptamine [5-HT, (10(-12) ~ 10(-4) mol/ L] were significantly enhanced in arterial rings isolated from 4-wk tail-suspended as compared with that from simultaneous control rats. CONCLUSION: These results indicate that medium-term simulated weightlessness may result in an enhanced contractile responsiveness in rat basilar artery, and strongly support the hypothesis of cerebrovascular syncope-initiating mechanism.

Aerospace Medicine↗

[Effects of simulated weightlessness on ultrastructure of soleus muscle spindle in rats].

OBJECTIVE: To study changes in ultrastructure of soleus muscle spindle induced by simulated weightlessness in rats. METHOD: Weightlessness was simulated by tail suspension in female rats. The ultrastructure of isolated soleus muscle spindle were observed in 4 d, 7 d, 14 d tail-suspended and 14 d recovered rats. RESULT: Chaotic myofibril, hyperplasia of mitochondria, and enlargement of terminal cisterna were found in the ultrastructure of isolated soleus muscle spindle in 4 d tail-suspended rats. The ultrastructure of isolated soleus muscle spindle in 7 d tail-suspended rats showed more distinct changes, while that in 14 d tail-suspended rats showed obvious retrograde changes. The ultrastructure of isolated muscle spindle in 14 d recovered rats after 14 d tail-suspension were similar to that of control group. CONCLUSION: Simulated weightlessness could induce time-related and reversible changes in ultrastructure of soleus muscle spindle in rats.

Animals↗

On the mechanisms of changes in skeletal muscles in the weightless environment.

Some characteristics of muscle contraction and mechanical properties of two muscles (M. soleus and M. extensor digitorum longus) in Wistar rats after 22 days of weightlessness have been investigated. On the second day after return to earth, the following changes were evident: slowing of twitch responses of the muscles studied; shortening half tetanic contraction time (defined by point of interactions of the increasing curve with 50% level of the peak value) in soleus; a rise of tension in both muscles as shown by the curve "length-force"; an increase of twitch/tetanus ratio and fatigability in both muscles. During repeated study of muscle properties, on the 26th day after return to earth, there were not any significant changes in values of most the above mentioned indices except the diminished strength of soleus. Shortening of contraction time in slow antigravitary soleus muscle is believed to be a sign of adaptive change in its characteristics resulting from unloading under the conditioning of weightlessness. Increased stiffness and diminished strength of muscles are considered as functional signs of atrophic processes, developing in the experiment. Dynamics of functional changes, conditioned, as we believe, mainly by weightlessness and correlated with morphological and biochemical data obtained on analogous material, allows us to postulate a reversible character of the changes described.

Adaptation, Physiological↗

[The effect of simulated weightlessness on the function of spleen lymphocytes and the expression of c-fos proto-oncogene in tail-suspended mice].

Objective. To investigate the effect of simulated weightlessness on proliferation of spleen lymphocyte, production of interleukin-2 and expression of c-fos proto-oncogene in mice. Method. Mice were tail-suspended for 7 or 14 days to simulate the effect of weightlessness; proliferation of lymphocyte was measured by MTT method, production of IL-2 was determined by biological activity and expression of c-fos proto-oncogene was determined by dot blotting. Result. As compared with the control, the proliferation of spleen lymphocyte and the production of IL-2 were significantly decreased in 14 d suspended group, but the expression of c-fos proto-oncogene [correction of oncogen] was increased in both 7 d and 14 d suspended groups. Conclusion. This result suggested that simulated weightlessness could interfere with the genes regulating the lymphocyte.

Animals↗

Dynamics of sleep patterns during prolonged simulated weightlessness.

Subjects immersed for 6 days in water, simulating weightlessness, exhibited marked changes in the total time spent in sleep and in the percentage of that time spent in each sleep stage. The length of time spent in Stage 4 deep sleep and in REM sleep decreased in the first half of the 6-day immersion period. During the latter half of the immersion period, a clear adaptive response was observed in the sleep patterns: the sequential appearance of the different stages of sleep and the percentage of time spent in the six stages of sleep showed a clear approach to the pre-immersion data. During the 3-day post-immersion period, the patterns approached the normal pre-immersion levels, although there was some overshoot or a negative phase period characterizing this approach. By the sixth day of immersion, the percentage of time spent in each stage of sleep had returned to near normal pre-immersion values, but the total time spent in sleep was still somewhat less than normal. This fact suggests that, once adapted to a condition of weightlessness, the sleep requirement may be less than during normal ambulatory life. During the post-immersion period, the pattern of Stage 4 sleep at early evening, midnight and dawn showed no special reactive characteristics, but rather a clear recovery towards the original pattern. On the other hand, at the duration of REM sleep, it overshot the pre-immersion values at the beginning of the post-immersion period, and then returned to the original pattern. These experiments suggest that some of the changes in sleep patterns which are observed under conditions simulating weightlessness may be adaptive.

Adaptation, Physiological↗

[Effects of simulated weightlessness on pressure-volume relationships of femoral vein of New Zealand Rabbits].

Objective. To observe the changes of pressure-volume relationships of rabbit femoral veins and their structural changes caused by simulated weightlessness. Method. Head-Down Tilt (HDT) -20 degrees rabbit model was used to simulate weightlessness. Twenty four healthy male New Zealand Rabbits were randomly divided into 21 d HDT group,10 d HDT group and control group, (8 in each group). Pressure-volume (P-V) relationship of rabbits femoral veins was measured and the microstructure of the veins was observed. Result. The femoral vein P-V relationship curves of HDT groups showed a larger volume change ratio than that of control group. This change was that 21 d HDT group was even more obvious than that of HDT-10 d group. B1 and B2 in quadratic equations of 21 d HDT group were significantly higher than the values of both 10 d HDT group and control group during expansion (inflow) and collapse (outflow) (P<0.01). The result of histological examination showed that the contents and structure of femoral vein wall of HDT-rabbits changed significantly. Endothelial cells of femoral vein became short and columnar or cubic, some of which fell off. Smooth muscle layer became thinner. Conclusion. Femoral venous compliance increased after weightlessness-simulation and the femoral venous compliance in 21 d-HDT rabbits increased more obviously than that in 10 d-HDT rabbits. The structure of femoral vein wall had changed obviously.

Adaptation, Physiological↗

[Changes of reactivity of rabbit femoral venous rings after 21 d simulated weightlessness].

OBJECTIVE: To study the effects of simulated weightlessness on reactivity of leg veins. METHOD: Vascular bathing technique was used to measure the contractile responses of rabbit femoral venous rings to Ht, PE and KCl, and the dilatory responses to ACh and SNP after horizontal confinement or head-down tilt confinement for 21 d. RESULT: After simulated weightlessness for 21 d, the contractile response of rabbit femoral venous rings to higher concentrations of PE and KCl decreased significantly (P<0.05); the contractile response to Ht also decreased, but not significantly (P>0.05); the dilatory responses to ACh and SNP did not change significantly in both groups. CONCLUSION: Contractile response of rabbit femoral vein decreased after simulated weightlessness for 21 d, which might partly explain the occurrence of orthostatic intolerance in men after space flight.

Acetylcholine↗

[Influence of simulated weightlessness on the morphology of nerve endings of muscle spindle in rat soleus muscle].

OBJECTIVE: To study changes in structure and innervation of soleus muscle spindle in rats induced by simulated weightlessness. METHOD: Weightlessness was simulated by tail suspension in female rats. The technique of Fawosky's Staining was used to detect the morphology of nerve endings of soleus muscle spindle in 7 d, 14 d, 21 d tail-suspended and control rats. RESULT: The intrafusal muscle fibers were regular and nerve endings were intact and clear in the soleus spindles of control rats. No obvious change was observed in muscle spindles of 7 d tail-suspended rats. Intrafusal muscle fibers became irregular, with rough and vague nerve endings in 14 d tail-suspended rats. The distinct retrograde change of muscle spindles and nerve endings were observed in 21 d tail-suspended rats. Degeneration and rupture were found in nerve endings, which made it unclear and pale in staining. CONCLUSION: Simulated weightlessness could induce time-related changes in structure and innervation of soleus muscle spindle in rats.

Animals↗

Effects of simulated weightlessness on myosin heavy chain expression of soleus intrafusal muscle fibers in rats.

OBJECTIVE: To examine the myosin heavy chain expression in intrafusal fibers in rat soleus muscle before and after simulated weightlessness and to analyse the mechanism involved in muscle spindle deterioration during simulated weightlessness. METHOD: The rats were divided into 3 groups: 7 d, 14 d tail-suspension group and control group. Control and experimental spindles were examined using monoclonal antibodies specific for myosin heavy chains of slow-tonic (ALD58) and fast-twitch (MF30) chicken muscles by the immunoperoxidase reaction utilizing the ABC (avidin-biotin-complex) method. RESULT: The extrafusal muscle fibers did not exhibit immunoreactivity to ALD58 and MF30. Only intrafusal fibers bound these antibodies. The bag 1 fiber and bag 2 fiber reacted to ALD58. The bag 2 fiber and chain fibers stained with MF30. After 7 d suspension the immunoreactivity of the bag 1 fiber and bag 2 fiber to ALD58 decreased, while the immunoreactivity of the bag 2 fiber and chain fibers to MF30 increased. After 14 d suspension the immunoreactivity of the bag 1 fiber and bag 2 fiber to ALD58 decreased remarkably, even disappeared. While all of the intrafusal fibers reacted to MF30 and the immunoreactivity increased obviously. CONCLUSION: The expression level and patterns of MHC in intrafusal fibers of rat soleus muscle changed after simulated weightlessness.

Animals↗

[Effects of weightlessness on phosphorus and calcium metabolism and bone remodeling].

Weightlessness results in negative calcium balance which can only reflect a redistribution of calcium in the body: the loss of calcium in the faeces and/or urine is constant, but an increase in urinary hydroxyproline indicating bone collagen destruction is not always detectable; moreover, a slowing down of collagen maturation may be suspected. Bone analysis by histomorphometry in animals and by indirect, non-invasive methods in man shows a decrease in bone mass. However, this bone tissue atrophy might only reflect excessive ageing of the bone during weightlessness, as suggested by slow bone formation and lack of variation in bone resorption. Since the experimental results obtained in men and animals during simulated weightlessness on earth are not strictly identical with those observed in space- flights, their validity may be questioned. Additional studies (notably histomorphometric studies) are therefore required for a better knowledge, as well as prevention, of the problems raised by human life in space.

Animals↗