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PubMed1990

Selective hypergravity stimulation: its effects on the human balance and gait functions. A model to assess, in normal gravity conditions, some aspects of the perturbations induced on human body by microgravity conditions.

To assess on Earth some reactions of the muscle mechanoreceptors to transitions from normogravity to microgravity, we studied the effects of transitions from hypergravity to normogravity. Hypergravity was selectively applied to the extensor muscles by increasing their activity during half an hour by means of 2 rubber extensible springs stretched from shoulders to feet. Immediate effects and post effects of such a stimulation were measured on quantifying dynamic balance (angular or linear displacement) and gait functions (spatio-temporal parameters and inferior limb length variations). The main results are: (1) a post effect on the balance function, appearing 3 minutes after the end of the selective hypergravity stimulus and improving the efficiency of balance function compared with the basal one, (2) a post effect on the gait function, appearing immediately after the end of the selective stimulation. It concerns the measures which quantify the gait phases during which flexor muscles are active (swing phases). It decreases the efficiency of the gait function compared with the basal one, It disappears 3 minutes after the end of the selective hypergravity stimulation. According to these results, if the effects on the muscle mechanoreceptors of the transitions from normogravity, to microgravity looks like those of transitions from hypergravity to normogravity, post effects could be a mechanism of the motor perturbations at the beginning of the orbital flights.

Adult↗
PubMed2003

Fos induction in the amygdala by vestibular information during hypergravity stimulation.

Altered gravity environments including both hypo- and hypergravity can elicit motion sickness. Vestibular information is known to be essential for motion sickness, but its other neural substrates are poorly understood. We previously showed that bilateral lesions of the amygdala suppressed hypergravity-induced motion sickness in rats, using pica behavior as an emetic index. We show in the present study that during hypergravity stimulation, vestibular information activated the central nucleus of the amygdala (CeA), as determined by the induction of Fos expression, in comparison between normal and bilaterally labyrinthectomized rats. The finding that Fos expression was confined to the CeA and almost completely absent in other subnuclei of the amygdala contrasted with many previous studies that used other stressful stimuli such as foot shock, restraint and forced swimming, suggesting a specific vestibular effects on the amygdala. Prolongation of hypergravity resulted in reduction of Fos expression in the CeA, suggesting a process of habituation. Such decreases appeared earlier than in the vestibular nucleus, suggesting that adaptive changes in the CeA to hypergravity were independent of changes in the vestibular input. Our results suggest the amygdala is a neural substrate involved in the development of and habituation to motion sickness.

Afferent Pathways↗
PubMed2002

Hypergravity modulates behavioral nociceptive responses in rats.

Hypergravity (2G) exposure elevated the nociceptive threshold (pain suppression) concomitantly with evoked neuronal activity in the hypothalamus. Young Wistar male rats were exposed to 2G by centrifugal rotation for 10 min. Before and after 2G exposure, the nociceptive threshold was measured as the withdrawal reflex by using the von Frey type needle at a total of 8 sites of each rat (nose, four quarters, upper and lower back, tail), and then rats were sacrificed. Fos expression was examined immunohistochemically in the hypothalamic slices of the 2G-treated rats. When rats were exposed to 2G hypergravity, the nociceptive threshold was significantly elevated to approximately 150 to 250% of the 1G baseline control levels in all the examination sites. The 2G hypergravity remarkably induced Fos expression in the paraventricular and arcuate nuclei of the hypothalamus. The analgesic effects of 2G hypergravity were attenuated by naloxone pretreatment. Data indicate that hypergravity induces analgesic effects in rats, mediated through hypothalamic neuronal activity in the endogenous opioid system and hypothalamo-pituitary-adrenal axis.

Animals↗
PubMed1998

Effects of pre- and perinatal exposure to hypergravity on muscular structure development in rat.

This study evaluated the influence of precocious exposure to hypergravity on the expression of myosin heavy chain (MHC) protein isoforms in nape, masticatory and respiratory developmental rat muscles. Pregnant females were maintained at 1.8 g from the 11th day of gestation to the 7th day after birth. The 7-day-old rats were used for muscle sampling. Hypergravity induced a marked decrease in the weight and protein content of all six muscles. Three MHC isoforms were detected in the young rats' muscles: embryonic (E), perinatal (P) and slow type 1 MHC. In centrifuged nape and masticatory muscles, there was a decrease in MHC E and an increase in P without reduction (indeed, even an increase) in MHC 1, whereas in the respiratory muscle MHC E was increased and MHC 1 decreased. These results indicate that hypergravity produces important changes in the contractile properties not only of antigravity muscles but also masticatory and respiratory muscles. MHC P has a higher shortening velocity than MHC E, which has a higher one than MHC 1. The hypergravity-induced transformations of MHC isoforms would thus lead to increased velocity of all muscles studied. In spite of the observation of a hypergravity-induced muscle hypotrophy, the results of this study reflect the adaptational properties of developing muscles to increased gravitational forces.

Animals↗
PubMed2004

Is lifespan extension accompanied by improved antioxidant defences? A study of superoxide dismutase and catalase in Drosophila melanogaster flies that lived in hypergravity at a young age.

It has been previously shown that exposing Drosophila melanogaster flies to hypergravity (3g or 5g) at a young age for 2 weeks increases male longevity, resistance to heat in both sexes, and delays behavioural ageing, but the causes of these effects are unknown. We hypothesised that these flies could be well protected against free radical attacks and, if this protection persists after removal from hypergravity, can better resist free radicals and finally live longer than flies that have always lived at 1g. If so, the activity of enzymes detoxifying free radicals superoxide dismutase and catalase should be increased in flies that have lived in hypergravity. Results showed that no effect of hypergravity on the activity of these enzymes was observed at 2, 4 or 6 weeks of age. The greater longevity of male flies that have lived in hypergravity at a young age thus cannot be explained by the activity changes of these major antioxidant enzymes.

Aging↗
PubMed1999

Hypergravity increases the molecular mass of xyloglucans by decreasing xyloglucan-degrading activity in azuki bean epicotyls.

Elongation growth of dark-grown azuki bean (Vigna angularis Ohwi et Ohashi cv. Takara) epicotyls was suppressed by hypergravity at 30 x g and above. Acceleration at 300 x g significantly decreased the mechanical extensibility of cell walls. The amounts of cell wall polysaccharides (pectin, hemicellulose-II and cellulose) per unit length of epicotyls increased under the hypergravity condition. Hypergravity also increased the amounts and the weight-average molecular mass of xyloglucans in the hemicellulose-II fraction, while decreasing the activity of xyloglucan-degrading enzymes extracted from epicotyl cell walls. These results suggest that hypergravity increases the amounts and the molecular mass of xyloglucans by decreasing xyloglucan-degrading activity. Modification of xyloglucan metabolism as well as the thickening of cell walls under hypergravity conditions seems to be involved in making the cell wall mechanically rigid, thereby inhibiting elongation growth of azuki bean epicotyls.

Cell Wall↗
PubMed2005

Influence of increased mechanical loading by hypergravity on the microtubule cytoskeleton and prostaglandin E2 release in primary osteoblasts.

Cells respond to a wide range of mechanical stimuli such as fluid shear and strain, although the contribution of gravity to cell structure and function is not understood. We hypothesized that bone-forming osteoblasts are sensitive to increased mechanical loading by hypergravity. A centrifuge suitable for cell culture was developed and validated, and then primary cultures of fetal rat calvarial osteoblasts at various stages of differentiation were mechanically loaded using hypergravity. We measured microtubule network morphology as well as release of the paracrine factor prostaglandin E2 (PGE2). In immature osteoblasts, a stimulus of 10x gravity (10 g) for 3 h increased PGE2 2.5-fold and decreased microtubule network height 1.12-fold without affecting cell viability. Hypergravity (3 h) caused dose-dependent (5-50 g) increases in PGE2 (5.3-fold at 50 g) and decreases (1.26-fold at 50 g) in microtubule network height. PGE2 release depended on duration but not orientation of the hypergravity load. As osteoblasts differentiated, sensitivity to hypergravity declined. We conclude that primary osteoblasts demonstrate dose- and duration-dependent sensitivity to gravitational loading, which appears to be blunted in mature osteoblasts.

Animals↗
PubMed2003

Chronic centrifugation (hypergravity) disrupts the circadian system of the rat.

The present study was conducted to evaluate the response of rat deep body temperature (DBT) and gross locomotor activity (LMA) circadian rhythms to acute hypergravity onset and adaptation to chronic (14 day) hypergravity exposure over three gravity intensities (1.25, 1.5, and 2 G). Centrifugation of unanesthetized naive animals resulted in a dramatic acute decrease in DBT (-1.45, -2.40, and -3.09 degrees C for the 1.25, 1.5, and 2.0 G groups, respectively). LMA was suppressed for the duration of centrifugation (vs. control period); the percent decrease for each group on days 12-14, respectively, was 1.0 G, -15.2%, P = not significant; 1.25 G, -26.9%, P < 0.02; 1.5 G, -44.5%, P < 0.01; and 2.0 G, -63.1%, P < 0.002. The time required for DBT and LMA circadian rhythmic adaptation and stabilization to hypergravity onset increased from 1.25 to 2.0 G in all circadian metrics except daily means. Periodicity analysis detected the phenomenon of circadian rhythm splitting, which has not been reported previously in response to chronic hypergravity exposure. Our analysis documents the disruptive and dose-dependent effects of hypergravity on circadian rhythmicity and the time course of adaptation to 14-day chronic centrifugation exposure.

Adaptation, Physiological↗
PubMed2004

Distributions of lung ventilation and perfusion in prone and supine humans exposed to hypergravity.

When normal subjects are exposed to hypergravity [5 times normal gravity (5 G)] there is an impaired arterial oxygenation that is less severe in the prone compared with supine posture. We hypothesized that under these conditions the heterogeneities of ventilation and/or perfusion distributions would be less prominent when subjects were prone compared with supine. Expirograms from a combined rebreathing-single breath washout maneuver (Rohdin M, Sundblad P, and Linnarsson D. J Appl Physiol 96: 1470-1477, 2004) were analyzed for vital capacity (VC), phase III slope, and phase IV amplitude, to analyze heterogeneities in ventilation (Ar) and perfusion [CO(2)-to-Ar ratio (CO(2)/Ar)] distribution, respectively. During hypergravity, VC decreased more in the supine than in the prone position (ANOVA, P = 0.02). Phase III slope was more positive for Ar (P = 0.003) and more negative for CO(2)/Ar (P = 0.007) in the supine compared with prone posture at 5 G, in agreement with the notion of a more severe hypergravity-induced ventilation-perfusion mismatch in supine posture. Phase IV amplitude became lower in the supine than in the prone posture for both Ar (P = 0.02) and CO(2)/Ar (P = 0.004) during hypergravity as a result of the more reduced VC in the supine posture. We speculate that results of VC and phase IV amplitude are due to the differences in heart-lung interaction and diaphragm position between postures: a stable position of the heart and diaphragm in prone hypergravity, in contrast to supine in which the weight of the heart and a cephalad shift of the diaphragm compress lung tissue.

Adult↗
PubMedDate not supplied

[Ultrastructure of muscle spindles (Mechanoreceptors) of Rat m. soleus after support unloading and its combination with hypergravity].

We used electron microscopy to evaluate the effect of support unloading of m. soleus in adult Wistar rats (restrained in an antiorthostatic posture for 23-24 h/day within 24 days) on the ultrastructure of the intrafusal fibers and motor neuromuscular junctions of the muscle spindles, as well as the efficiency of intermittent hypergravity (+2Gz; 1 h/day for 19 days in a centrifuge in hypokinetic cages) as a countermeasure used in conditions of support unloading of this muscle. In the absence of support on the hind limbs, most of intrafusal fibers of m. soleus preserved the typical ultrastructure, while the axon terminals of the neuromuscular junctions accumulated a lot of synaptic vesicles (including large vesicles); the coated vesicles were absent due to unloading of the muscle and its muscle spindles (no contractions of the intrafusal fibers). A short-term effects of hypergravity at the background of support unloading of m. soleus mostly induced static loading of the muscle inducing different responses of the intrafusal fibers in different regions of the muscle spindles: local lysis of myofilaments was observed in single intrafusal fibers of the equatorial and intracapsular motor regions, while myofibrils remained intact in most fibers in the intra- and extracapsular regions of the spindles. The revealed adaptive response of the intrafusal fibers is, on the one hand, due to their specific innervation and ultrastructure and, on the other hand, to positive effect of hypergravity on the motor and extracapsular regions of the muscle spindles. Hypergravity decreased the number of synaptic vesicles and induced appearance of the coated vesicles in the axon terminals of the neuromuscular junctions of the intrafusal fibers in the animals restrained in an antiorthostatic posture (support unloading of m. soleus), which is due to increased functional load of the muscle. The ultrastructure of the muscle fibers adequately reflected the functional status of the postural m. soleus both during support unloading and support unloading combined with hypergravity load.

Actin Cytoskeleton↗
PubMed2006

Dose-dependent effects of hypergravity on body mass in mature rats.

INTRODUCTION: Previous reports have shown that exposure to hypergravity decreases rat body mass during the initial phase, with this decrease and level of gravity showing a dose-response relationship. The present study examined whether rate of body mass gain after the initial phase of exposure is attenuated by hypergravity in a dose-dependent manner and sought to identify any threshold. METHODS: Male 10-wk-old rats (n = 64) were used, with 16 rats serving as 1.0-G controls, and 48 rats exposed to hypergravity for 14 d in 4 groups (1.5, 2.0, 2.5, and 3.5 G; n = 12 each). Body mass gain was evaluated according to slope of change in body mass from day 7 of exposure to hypergravity, as both absolute and relative values. RESULTS: Slopes of body mass gain did not differ between the 1.0- and 1.5-G groups (6.09 and 5.75 g x d(-1), respectively), but were significantly less for the 2.0-, 2.5-, and 3.5-G groups (4.91, 3.03 and 1.99 g x d(-1), respectively) than for the 1.0- and 1.5-G groups. Body mass gain as a relative value did not differ between the 1.0-, 1.5-, and 2.0-G groups (1.5 +/- 0.2, 1.6 +/- 0.6 and 1.4 +/- 0.3 g x d(-1) x 100 g(-1) body mass, respectively), but was significantly less for the 2.5- and 3.5-G groups (1.1 +/- 0.6 and 0.8 +/- 0.3 g x d(-1) x 100 g(-1) body mass, respectively) than for the 1.0-, 1.5-, and 2.0-G groups. Absolute values and rate of body mass gain were reduced with increases in gravity. CONCLUSION: Exposure to hypergravity attenuates body mass gain in a dose-dependent manner, with a threshold possibly existing between 1.5- and 2.5-G for 10-wk-old male rats.

Animals↗
PubMed1981

Enhanced skeletal muscle insulin sensitivity in year-old rats adapted to hypergravity.

Rats adapted to hypergravity by continuous centrifugation at 4.15 g for 7 mo exhibit increased glucose uptake at lower plasma insulin levels than weight-matched control animals following oral glucose administration. To assess insulin sensitivity of specific tissues, glucose uptake by perfused skeletal muscle and liver from year-old hypergravic rats was compared with perfused tissue from weight-matched control rats (2.5-mo-old). The results show that metabolic clearance of glucose by skeletal muscle from hypergravic rats ws not significantly greater than control muscle when perfused in the absence of insulin (10.6 vs. 8.1 microliter.min-1.g muscle-1) but was twofold faster (23.0 vs. 9.5) at perfusate insulin levels of 35 microunits/ml. Conversely, glucose uptake by hypergravic livers was significantly decreased (P less than 0.001) compared with control livers (10.3 vs. 27.8) at perfusate insulin levels of 40 microunits/ml. These findings suggest that skeletal muscle rather than liver is the tissue primarily responsible for enhanced sensitivity to insulin observed in older rats adapted to hypergravity.

Adaptation, Physiological↗
PubMed1991

Ultrastructural studies on the effects of hypergravity environment on the parathyroid glands in golden hamsters of different ages.

The ultrastructure of the parathyroid glands of infantile, young, adult and senile golden hamsters subjected to a hypergravity environment was studied. In the parathyroid glands of 5-, 10- and 20-day-old, and 1- and 3-month-old golden hamsters exposed to a hypergravity environment, the Golgi complexes were significantly increased, and in 5-, 10- and 20-day-old, and 1- and 8-month-old animals exposed to a hypergravity environment, the cisternae of the granular endoplasmic reticulum appeared to be increased as compared to those of each control group. In addition, in centrifuged animals numerous prosecretory granules were observed in the Golgi areas, and many secretory granules were located in the peripheral cytoplasm. The ultrastructure of the parathyroid glands of 14-month-old centrifuged animals resembled that of 14-month-old control animals. These results suggest that the secretory activity of the parathyroid gland may be stimulated in infantile, young and adult golden hamsters subjected to a hypergravity environment and may not be stimulated in senile animals subjected to a hypergravity environment.

Aging↗
PubMed2001

Hormonal modulation of food intake in response to low leptin levels induced by hypergravity.

A loss in fat mass is a common response to centrifugation and it results in low circulating leptin concentrations. However, rats adapted to hypergravity are euphagic. The focus of this study was to examine leptin and other peripheral signals of energy balance in the presence of a hypergravity-induced loss of fat mass and euphagia. Male Sprague-Dawley rats were centrifuged for 14 days at gravity levels of 1.25, 1.5, or 2 G, or they remained stationary at 1 G. Urinary catecholamines, urinary corticosterone, food intake, and body mass were measured on Days 11 to 14. Plasma hormones and epididymal fat pad mass were measured on Day 14. Mean body mass of the 1.25, 1.5, and 2 G groups were significantly (P < 0.05) lower than controls, and no differences were found in food intake (g/day/100 g body mass) between the hypergravity groups and controls. Epididymal fat mass was 14%, 14%, and 21% lower than controls in the 1.25, 1.5, and 2.0 G groups, respectively. Plasma leptin was significantly reduced from controls by 46%, 45%, and 65% in the 1.25, 1.5, and 2 G groups, respectively. Plasma insulin was significantly lower in the 1.25, 1.5, and 2.0 G groups than controls by 35%, 38%, and 33%. No differences were found between controls and hypergravity groups in urinary corticosterone. Mean urinary epinephrine was significantly higher in the 1.5 and 2.0 G groups than in controls. Mean urinary norepinephrine was significantly higher in the 1.25, 1.5 and 2.0 G groups than in controls. Significant correlations were found between G load and body mass, fat mass, leptin, urinary epinephrine, and norepinephrine. During hypergravity exposure, maintenance of food intake is the result of a complex relationship between multiple pathways, which abates the importance of leptin as a primary signal.

Animals↗
PubMed1991

Influence of hypergravity on the pH profile and proteolytic activity of the avian gastrointestinal tract.

The present study deals with the effect of hypergravity (2xg) on the pH and on the proteolytic activity in the digesta of the gastrointestinal tract of Japanese quails during intense growth. The birds were raised on a semisynthetic diet containing free amino acids (A) and a commercial diet (B). During days 35 till 40 post-hatching the quails were exposed to hypergravity (2xg) using a specially designed centrifuge. On days 40 (experimental group, 2xg) and 41 (control group, 1xg) the animals were sacrificed. The pH of the digesta in various segments of the gastrointestinal tract was measured by means of a semi-microelectrode. Total proteolytic activity was determined by means of azo-dye-modified proteins serving as general proteolytic substrates. Hypergravity leads in general to an alkalization of digesta in various parts of the gastrointestinal tract. In case of the gizzard and duodenum (diet A) and also in the distal jejunum (diet B) the differences are significant. With both diets, hypergravity leads to a considerable decrease in the total proteolytic activity. The reduction is most expressed in the duodenum and jejunum. Changes in the pH of digesta compensate for the decrease in the proteolytic activity. This may explain why hypergravity per se does not seem to impair growth of the Japanese quails.

Amino Acids↗
PubMed1979

Hypergravity: its effect on the estrous cycle and hormonal levels in female rats.

Hypergravity at 1.02-2.28 g was simulated by centrifugation and the estrous cycles of rats were followed by testing vaginal smears. Associated hormonal changes were measured from blood samples by radioimmunoassay. It was found that moderate hypergravity affects the estrous cycle by prolonging the diestrous period, and this effect seems to bear a direct relationship to the strength and timing of the hypergravity. Intermittent centrifugation produces the same effect as continuous centrifugation. After the prolonged diestrous, the estrous cycle returns to normal. The observed effects were associated with hormonal changes. Progesterone was elevated during the prolonged diestrous although no consistent changes in estrogen levels could be found. The effect of simulated hypergravity resembles the pseudo-pregnancy response produced in rats by various stimuli, but a decidual reaction, i.e., the usual uteral growth as a response to pregnancy or injury during pseudo-pregnancy, could not be elicited during the prolonged diestrous induced by 2.08 g. The possible mechanism eliciting the prolongation of diestrous is discussed.

Animals↗
PubMed2004

Environmental impacts on the developing CNS: CD15, NCAM-L1, and GFAP expression in rat neonates exposed to hypergravity.

We have previously reported that the developing rat cerebellum is affected by hypergravity exposure. The effect is observed during a period of both granule and glial cell proliferation and neuronal migration in the cerebellum and coincides with changes in thyroid hormone levels. The present study begins to address the molecular mechanisms involved in the cerebellar response to hypergravity. Specifically, the study focuses on the expression of cerebellar proteins that are known to be directly involved in cell-cell interactions [protein expressing 3-fucosyl-N-acetyl-lactosamine antigen (CD15), neuronal cell adhesion molecule (NCAM-L1)] and those that affect cell-cell interactions indirectly [glial fibrillary acidic protein (GFAP)] in rat neonates exposed to centrifuge-produced hypergravity. Cerebellar mass and protein expression in rat neonates exposed to hypergravity (1.5 G) from gestational day (G) 11 to postnatal day (P) 30 were compared at one of six time points between P6 and P30 against rat neonates developing under normal gravity. Proteins were analyzed by quantitative western blots of cerebellar homogenates prepared from male or female neonates. Cerebellar size was most clearly reduced in male neonates on P6 and in female neonates on P9, with a significant gender difference; differences in cerebellar mass remained significant even when change in total body mass was factored in. Densitometric analysis of western blots revealed both quantitative and temporal changes in the expression of selected cerebellar proteins that coincided with changes in cerebellar mass and were gender-specific. In fact, our data indicated certain significant differences even between male and female control animals. A maximal decrease in expression of CD15 was observed in HG females on P9, coinciding with maximal change in their cerebellar mass. A shift in the time-course of NCAM-L1 expression resulted in a significant increase in NCAM-L1 in HG males on P18, an isolated time at which cerebellar mass does not significantly differ between HG and SC neonates. A maximal decrease in expression of GFAP was observed in HG males on P6, coinciding with maximal change in their cerebellar mass. Altered expression of cerebellar proteins is likely to affect a number of developmental processes and contribute to the structural and functional alterations seen in the CNS developing under altered gravity. Our data suggest that both cerebellar development and its response to gravitational manipulations differ in males and females.

Animals↗
PubMed1998

The white blood cell line: changes induced in mice by hypergravity.

The effect of hypergravity on the white blood cell (WBC) line of mice was investigated by use of horizontal centrifuge. Several sets of experiments were performed, in which the parameters measured were the WBC and differential cell count in the peripheral blood. In another experiment, lymphocyte counts from the spleen, lymph nodes, and the thymus were measured. The needed samples were taken from the mice during a stay of 7-40 days under a hypergravity of 1.6G. The test groups that were placed on the arms of the centrifuge (1.6G) were compared with stationary control groups (1G) and a rotating control group located at the center of the centrifuge (1G). Such a comparison revealed the test animals to be deficient on all counts, to wit, showing a decrease in total number of WBC's, a decrease in lymphocyte number in the peripheral blood and a decrease in the number of lymphocyte in the spleen and thymus. The decrease of lymphocytes in peripheral blood was characterized by two different slopes--an early and temporary decrease at the first days of the experiment evident in both test and rotating control groups followed by a temporary increase, and a later persistent decrease, evident only in the test group, while in the rotating control lymphocyte counts reverted to normal. There were no significant differences in monocyte or neutrophil counts, except for a temporary increase in the number of neutrophils which peaked on the seventh day. In order to evaluate the effect of hypergravity on restoration of hematopoiesis following hematopoietic suppression, 5-fluoro-uracil (5-FU) was administered i.v. to both the experimental and control mice. Suppression of bone marrow was observed in all groups injected with 5-FU, but while there was later an increase in cell counts in the control groups, there was no such increase in the test group subjected to hypergravity.

Animals↗