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At least 19 recordsLinked to original sources

Hypogravity-induced atrophy of rat soleus and extensor digitorum longus muscles.

Prolonged exposure of humans to hypogravity causes weakening of their skeletal muscles. This problem was studied in rats exposed to hypogravity for 7 days aboard Spacelab 3. Hindlimb muscles were harvested 12-16 hours postflight for histochemical, biochemical, and ultrastructural analyses. The majority of the soleus and extensor digitorum longus fibers exhibited simple cell shrinkage. However, approximately 1% of the fibers in flight soleus muscles appeared necrotic. Flight muscle fibers showed increased glycogen, lower subsarcolemmal staining for mitochondrial enzymes, and fewer subsarcolemmal mitochondria. During atrophy, myofibrils were eroded by multiple focal losses of myofilaments; lysosomal autophagy was not evident. Tripeptidylaminopeptidase and calcium-activated protease activities of flight soleus fibers were significantly increased, implying a role in myofibril breakdown. Simple fiber atrophy appears to account for muscle weakening during spaceflight, but fiber necrosis is also a contributing factor.

Aminopeptidases↗

A genetic effect of altered gravity: mutations induced by simulated hypogravity and hypergravity in microsatellite sequences of human tumor cells.

To determine the possible genetic effects of gravity alterations, we analyzed mutation induction in microsatellite sequences of human tumor cells treated with simulated hypogravity provided by a clinostat or hypergravity by a centrifuge. Microsatellite mutations were detected as changes in the size of polymerase chain reaction (PCR)-amplified allelic markers. The frequencies of mutant clones in cultures treated with simulated hypogravity for 24 or 48 h were almost the same as those of controls, but after 72 h of treatment, the mutant frequencies had increased significantly in all three microsatellite loci examined. Significantly higher mutant frequencies were similarly detected in cultures treated for 72 h with a hypergravity condition as low as 18xg, but not detected in 24 or 48 h treated cultures. These findings clearly show that gravity alterations that last for 3 days can induce microsatellite mutations in human cells. A genetic effect of gravity change, therefore, is established for the first time. Moreover, high frequencies of microsatellite mutations were induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) which activates protein kinase C-mediated signal transduction pathways and causes genetic instability. These findings suggest that gravity change induces microsatellite mutations by modulating the pattern of gene expression involved in signal transduction pathways.

DNA Primers↗

The immune system: effects of hypergravity and hypogravity.

The force of gravity has been inescapable until only the last few decades. Space programs conducted by several nations now make possible the study of hypergravity and hypogravity in a variety of scientific areas. Although much work has focused on the physiological aspects of gravity, its effects on the immune system are only beginning to be appreciated. An understanding of these effects is not only of theoretical interest, but important in predicting the health of astronauts exposed to hypergravity and hypogravity. These studies may also help to answer the larger question of how stress affects the immune response.

Animals↗

Three molecular mechanisms to explain some biological effects of electromagnetic fields and hypogravity.

There are many reports about the biological effects of electromagnetic fields and hypogravity and there have been many attempts to develop a theoretical explanation of this phenomenon. In this work, a mechanism is described based on the action of these physical environmental factors on single electrically charged groups from amino acids and considering the elongation stage of the protein synthesis as one of the main targets for both factors. For some rapid bioeffects after short exposures, a direct action on the conformation of the binding site of proteins is postulated. The other mechanism described here is based on the effect of these factors on the motion of the ionized calcium at the extracellular fluid. Many reports about the influences of electromagnetic and gravitational fields on gene expression, enzyme activity, bone mineralization, and oncogenesis are discussed, taking into account the new molecular mechanisms.

Animals↗

Cardiovascular responses to repetitive exposure to hyper- and hypogravity states produced by parabolic flight.

Physiologic changes to repetitive hyper- and hypogravity stresses occurring during eight to ten parabolas on NASA's KC-135 aircraft were studied. Hemodynamic responses in 11 subjects in 4 different postures (supine, standing, sitting, and semisupine Space Shuttle launch position) were determined using noninvasive impedance cardiography. Five seconds of heart rate, cardiac index, thoracic fluid index, stroke index, ejection velocity index, and ventricular ejection time data were averaged during four different gravity (g) states: 1.3g (before parabola onset); 1.9g (parabola entry); 0g (parabola peak); and 1.7g (parabola exit) for each subject. The standing position was associated with the largest changes in the cardiovascular response to hypo- and hypergravity. The thoracic fluid index did not indicate a headward redistribution during transition from a simulated launch position to weightlessness. Analysis of the eight to ten parabolas revealed that, in general, values obtained at 1.8g differed from 1.6g, 0g differed from 1.6 and 1.3g, and 1.6g differed from 1.3g. The factors of gravity, thoracic fluid index, and cardiac index exhibited significant differences that were most likely to occur between parabola 1 versus parabolas 6, 7, and 8, and parabola 2 versus parabolas 4 through 8. Only the parameter of thoracic fluid index exhibited significance for parabolas 3 versus parabolas 6 and 7.

Adult↗

The effect of hypogravity and hypergravity on cells of the immune system.

This article reviews the gravity effects discovered in T lymphocytes and other cells of the immune system. The strong depression of mitogenic activation first observed in an experiment conducted in Spacelab 1 in 1983 triggered several other investigations in space and on the ground in the clinostat and in the centrifuge in the past 10 years. During this period, great progress was made in our knowledge of the complex mechanism of T cell activation as well as the technology to analyze the lymphokines produced during stimulation. Nevertheless, several aspects of the steps leading to activation are not yet clear. Studies in hypogravity and hypergravity may contribute to answering some of the questions. A recent investigation in the U.S. Spacelab SLS-1, based on a new technology in which leukocytes are attached to microcarrier beads, showed that the strong inhibition of activation in microgravity is due to a malfunction of monocytes acting as accessory cells. In fact, interleukin-1 production is nearly nil in resuspended monocytes, whereas T cell activation is doubled in attached cells. In hypergravity, but not at 1g, concanavalin A bound to erythrocytes activates B lymphocytes in addition to T cells. The activation of Jurkat cells is also severely impaired in space. These recent results have raised new questions that have to be answered in experiments to be conducted in space and on Earth in this decade. The experimental system, based on the mitogenic activation of T lymphocytes and accessory cells attached to microcarriers, offers an optimum model for studying basic biological mechanisms of the cell to assess the immunological fitness of humans in space and to test the feasibility of bioprocesses in space as well as on Earth.

Gravitation↗

Responses of lateral hypothalamic neurons to simulative hypogravic condition induced by body suspension.

In unanesthetized rats, neuronal activity in the lateral hypothalamic area was recorded during horizontal and head-down tilt suspension. When the rat was raised in the horizontally suspended position, 21 of 44 neurons changed activity as follows: immediate increase (7/21, Type I), immediate decrease (3/21, Type II), and gradual decrease (11/21, Type III). When the rat was raised with a head-down tilt position, the responses were suppressed in about half of the neurons tested. These results showed that the LHA neurons altered their activity in response to low G simulation induced by body suspension. Possible signals which induce the changes in the LHA neuronal activity, and an involvement of the LHA in the autonomic reflexes under hypogravic condition are discussed.

Animals↗

Hyper- and hypogravity alter posture in rats compensated on Earth for a vestibular asymmetry.

Head posture and neck muscle activity (EMGs) were examined in unilateral (UL) and bilateral (BL) vestibularly lesioned rats in hypergravity (1.7 g) and hypogravity (0 g) during parabolic flights. Compared with BL rats taken as control, the head and the body of UL deviated toward the lesion side at 0 g and toward the intact side at 1.7 g. Recorded in head fixed condition, left and right EMGs remained symmetrical in BL while UL rats displayed an asymmetry between left and right muscles at 1.7 g, but not at 0 g. These results demonstrate that an experimental otolithic asymmetry, compensated on Earth, can become unbalanced in altered gravity. Paradoxically, the utricular system appears to play a major role in that process.

Animals↗

Simulating certain aspects of hypogravity: effects on bone maturation in the non-weight bearing skeleton.

This study reports the effects of simulation of certain aspects of hypogravity (via partial skeletal unloading) on the growth and maturation of the non-weight bearing mandibles of 41-d and 1-yr-old rats. Partial skeletal unloading was effected by elevating the hindquarters (PULEH), and this simulation was controlled with normally loaded animals fed either ad libitum or the average amount of food consumed by the the experimental group (group-mean fed). The chemical status of the mandibles after 10 d or 14 d PULEH closely resembled that of control rats. The younger PULEH rats and their group-mean fed controls demonstrated a trend toward impaired maturation of mineral and matrix moieties; yet the concentrations of calcium (Ca) and phosphorus (P) expressed as a ratio to collagen hydroxyproline content were normally distributed within a density gradient profile which separates the mineral and matrix moieties into various age-dependent fractions. These data demonstrate that 10 d or 14 d PULEH in young or old rats, respectively, is not sufficient to elicit the maturation deficit observed in the mandibles of rats flown for 18.5 d in the Soviet Biosatellite Cosmos-1129. Unless the duration of PULEH is critical, the cephalad fluid shift which is common to PULEH and spaceflight animals cannot be solely responsible for the flight-induced maturation deficit. Because the mandibles of the PULEH rats remain antigravity-postured, the results emphasize the importance of gravity unloading to the impairment of mandibular bone matrix/mineral maturation during spaceflight. Decreased gravity and, hence, gravity unloading cannot be mimicked in ground-based models of hypokinesia.

Age Factors↗

Effect of hypogravity on human lymphocyte activation.

Cultures of human lymphocytes were exposed to the mitogen concanavalin A in a low-G environment generated by a fast rotating clinostat. DNA-synthesis was determined by incorporation of 3H-thymidine as the parameter for activation, cell ultrastructure was analyzed by electron microscopy, and cell movements were recorded by a cinecamera. The results were compared with 1-G controls. The cells cultured at low G show: (i) depression of activation by 50%, (ii) appearance of "mitochondria-rich" cells, and (iii) enhanced formation of pseudovilli and uropods. Our investigations in vitro at low and high G and reports on the effect of spaceflights on lymphocytes from cosmonauts and astronauts suggest that hypogravity depresses, whereas hypergravity enhances, lymphocyte activation by mitogens. This study is complementary to an experiment which will study the in vitro activation of lymphocytes in weightlessness during the first Spacelab mission.

Cell Movement↗

Hypogravity increases cyclopiazonic acid sensitivity of rat soleus muscle.

The functional capacity of skeletal muscle sarcoplasmic reticulum was explored in slow rat soleus muscle after 21 days of hindlimb suspension. The sarcoplasmic reticulum function was assessed in intact and saponin-skinned fibers by using cyclopiazonic acid, a specific Ca(2+)-adenosinetriphosphatase inhibitor. After hindlimb unweighting, the sensitivity to cyclopiazonic acid of intact and skinned soleus fibers becomes similar to that found in fast-twitch muscles. This change could be related to the expression of fast Ca2(+)-adenosinetriphosphatase-pump protein in unloaded soleus muscles and agrees with a transformation of soleus muscle from slow- to fast-twitch type. These results also indicate that specific pharmacological tools, like cyclopiazonic acid, could be used to analyze subcellular functional changes due to hindlimb unweighting.

Animals↗

Changes in kidney response to ADH under hypogravity: rat models and possible mechanisms.

Brattleboro homo- (DI) and heterozygous (HZ) rats with total or partial deficiency of the antidiuretic hormone (ADH) and also 10-14-day old Wistar rats irresponsive to ADH were used to examine the possible causes of inadequate responses to ADH in cosmonauts after space flights and in humans after prolonged bedrest in antiorthostasis (-60). The experimental results suggested that changes in the intrarenal osmotic gradients, as well as in the aggregate state of the ADH receptors as a result of the decreased ADH blood level under hypogravitation, might be a cause of the inadequate response to ADH in cosmonauts during readaptation to the Earth's gravity.

Animals↗