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Effect of hypergravity on the mouse basal expression of NGF and BDNF in the retina, visual cortex and geniculate nucleus: correlative aspects with NPY immunoreactivity.

We investigated the effect of hypergravitation on Nerve growth factor (NGF) and Brain-derived-neurotrophic factor (BDNF) expression in the visual cortex, geniculate nucleus (GN), and retina of adult male mice. The results showed that altered gravity causes an increase in NGF and BDNF in the visual cortex and GN which resulted to be associated with an up-regulation of cells immunoreactive to neuropeptide Y (NPY) in the visual cortex and GN. We also found a decrease in NGF, BDNF, and NPY in the mouse retina exposed to hypergravity. These findings suggest that alteration in gravitational environment differentially affects local neurotrophic factors and NPY expression. The possible functional significance of these observations is discussed.

Animals↗

The horizontal vestibulo-ocular reflex of hypergravity rat at different gravity levels.

The horizontal vestibulo-ocular reflex (VOR) of two groups of rats was measured. One group was bred and kept under hypergravity (HG; 2.5 g) conditions, the other group lived under normal gravity (NG; 1 g). Eye position was recorded in response to horizontal rotatory stimuli. Measurements were made under NG (1 g), and during parabolic flight (0.0 and 1.8 g). For both groups, the response to a rotatory stimulus during parabolic flight is similar to the response that was observed under 1 g conditions. In general, however, the VOR of HG rats is reduced by 20-50% relative to the response of NG rats and the phase is shifted by -40 degrees. We conjecture that this amplitude reduction and phase shift are the consequence of living in a rotating system.

Animals↗

Effects of acute and repeated daily exposure to hypergravity on spatial learning in mice.

Studies in humans have revealed that exposure to altered gravity may lead to impairments in cognitive functions. The objective of this study was to test whether mice exposed to hypergravity using a centrifuge apparatus showed learning impairments in a spatial learning task. Mice rotating at 1G or at 2G acceleration gravity and non-rotating controls were tested for reactivity to a spatial change after either a single 1 h or five repeated 1 h daily rotations in the centrifuge. While no differences among groups were found in the performance after single exposure to altered gravity, 5 days of repeated exposures to 1G or 2G gravity conditions significantly affected mouse ability to discriminate a new spatial arrangement. Additionally, this effect was stronger in the animals repeatedly exposed to 2G rather than to 1G conditions.

Animals↗

Vestibular-induced behaviour of rats born and raised in hypergravity.

One group of rats were bred and kept under hypergravity (HG) conditions (2.5 g) in a centrifuge. Another group were bred and kept under normal gravity conditions (1 g). Rats from both groups were dropped from a supine position into a water basin under infrared illumination leaving only gravity (1 g for both groups) for orientation. The airrighting reflex and reappearance at the water surface were examined. The success rate for airrighting of HG rats is 47% versus 45% for controls, and is performed about equally fast by both groups. The success rate of HG and control hamsters is </=25% and >/=80%, respectively [22]. This interspecific difference does not appear to support the conjecture that altered behaviour is caused by a structural change of vestibular end organs during ontogenetic development under HG. The success rate for surfacing of control rats is 100%. Surfacing of young HG rats is less successful (36% at age 6 weeks) and requires more time. On average, surfacing of adult rats of both groups is about the same. Apparently, the repeated stay of centrifuge-bred rats at 1 g for experiments and daily care suffices to recalibrate and improve their orientation, which is essential for surfacing.

Adaptation, Physiological↗

Effects of hypergravity on the morphological properties of the vestibular sensory epithelium. II. Life-long exposure of rats including embryogenesis.

Rats were exposed to a hypergravity (HG) level of 2.5 x g from conception until the age of 14 weeks. The vestibular epithelia of four of these animals and four control animals were immunohistochemically labeled for actin and tubulin. The apical cross-sectional area of epithelial cells of HG exposed rats appeared to be larger in all end organs. Area increase was 7.0% in the utricle (p<0.005) and 8.2% in the crista (p<<0.001). Hair cells and supporting cells appeared to be intact. The cellular arrangement and the proportion of different cell types within the epithelia was normal.

Actins↗

A review of the effects of microgravity and of hypergravity on aging and longevity.

This article reviews the literature dealing with the effects of acute or chronic exposure to microgravity (spacecrafts) or hypergravity (centrifuge) on longevity and the aging process. Even if space flights are now common, the effects of these two kinds of environment on aging are still poorly documented, particularly in mammals. However, there is a growing interest for the use of the fruit fly Drosophila melanogaster, and this species may be now considered as a model organism in gravitational biology studies dealing with aging.

Aging↗

Morphometry of fish inner ear otoliths after development at 3g hypergravity.

Size and asymmetry (size difference between the left and right sides) of inner ear otoliths of larval cichlid fish were determined after a long-term stay in moderate hypergravity conditions (3g; centrifuge), in the course of which the animals completed their ontogenetic development from hatch to freely swimming. Neither the normal morphogenetic development nor the timely onset and gain of performance of swimming behaviour were impaired by the experimental conditions. However, both utricular and saccular otoliths (lapilli and sagittae, respectively) were significantly smaller after hyper-g exposure compared to 1g control specimens raised in parallel. The asymmetry of sagittae was significantly increased in the experimental animals, whereas the respective asymmetry of lapilli was pronouncedly decreased compared with the 1g controls. These findings suggest that growth and development of bilateral asymmetry of otoliths are guided by the environmental gravity vector. Some of the hyper-g animals revealed a kinetotic behaviour on transfer to normal 1g earth conditions, which was similar to the behaviour observed in previous experiments on the transfer from 1g to microgravity (parabolic aircraft flights). The lapillar asymmetry of kinetotic samples was found to be significantly higher than that of normally behaving experimental specimens. No differences in asymmetry of sagittae were obtained between the two groups. This supports an earlier theoretical concept, according to which human static space sickness might be based on asymmetric utricular otoliths.

Animals↗

Impact of microgravity and hypergravity on free-running circadian rhythm of the desert beetle Trigonoscelis gigas Reitt.

Free-running circadian rhythms of locomotor activity of Tenebrionid beetles Trigonoscelis gigas Reitt., taken from the Turkmenian sand desert, were monitored in DD. The effects of microgravity --11 days in space flight aboard the Russian BION-10 "COSMOS" satellite, and of 2G hypergravity--seven days on a centrifuge, were determined. Two kinds of effects were found. In stable 2-peak records, there was a moderate decrease of tau in microgravity and an increase of tau in 2G, both of about 0.3 hr. In unstable records, alterations of gravity caused drastic deviations of tau and phi. Remarkably, two peaks of the activity rhythm, which are supposed to be controlled by separate oscillators, responded to gravity transitions in different ways. Gravity effects on the circadian system could be explained from a direct effect on the oscillator(s) itself or from a feed-back by altered locomotion to the pacemaker. Thus, for the first time the gravity dependence of a free-running circadian rhythm was proved in a combination of real space flight and centrifuge experiments.

Adaptation, Physiological↗

Effects of microgravity and hypergravity on aging and longevity of insects.

The effects of microgravity and hypergravity on aging are still poorly documented, particularly in mammals. However, there is a growing interest for the use of the fruit fly, Drosophila melanogaster, and this species may be now considered as a model organism in gravitational biology studies dealing with aging.

Age Factors↗

Tolerance of snakes to hypergravity.

Sensitivity of carotid blood flow to increased gravitational force acting in the head-to-tail direction(+Gz) was studied in diverse species of snakes hypothesized to show adaptive variation of response. Tolerance to increased gravity was measured red as the maximum graded acceleration force at which carotid blood flow ceased and was shown to vary according to gravitational adaptation of species defined by their ecology and behavior. Multiple regression analysis showed that gravitational habitat, but not body length, had a significant effect on Gz tolerance. At the extremes, carotid blood flow decreased in response to increasing G force and approached zero near +1 Gz in aquatic and ground-dwelling species, whereas in climbing species carotid flow was maintained at forces in excess of +2 Gz. Tolerant (arboreal) species were able to withstand hypergravic forces of +2 to +3 Gz for periods up to 1 h without cessation of carotid blood flow or loss of body movement and tongue flicking. Data suggest that the relatively tight skin characteristic of tolerant species provides a natural antigravity suit and is of prime importance in counteracting Gz stress on blood circulation.

Acceleration↗

Microgravity and hypergravity effects on fertilization of the salamander Pleurodeles waltl (urodele amphibian).

Effects of microgravity (microG) on fertilization were studied in the urodele amphibian Pleurodeles waltl on board the MIR space station. Genetic and cytomorphologic analyses ruled out parthenogenesis or gynogenesis and proved that fertilization did occur in microG. Actual fertilization was demonstrated by the analysis of the distribution of peptidase-1 genes, a polymorphic sex-linked enzyme, in progenies obtained in microG. Further evidence of fertilization was provided by the presence of spermatozoa in the perivitelline space and in the fertilization layer of the microG eggs and by the presence of a female pronucleus and male pronuclei in the egg cytoplasm. Experiments in microG and in 1.4G, 2G, and 3G hypergravity showed for the first time that, compared to eggs in 1G, several characteristics of the fertilization process including the cortical reaction and the microvillus transformations were altered depending on the gravitational force applied to the eggs. Microvillus elevation, the most evident feature, was reduced on microG-eggs and amplified on eggs submitted to 2G and 3G. No lethal consequences of these alterations on the early development of microG-eggs were observed.

Animals↗

The effect of hypergravity on the inner ear: CREB and syntaxin are up-regulated.

cDNA microarray analysis of differential mRNA expression in the rat inner ear under hypergravity identified 20 up-regulated and 2 down-regulated genes. The results demonstrated that various response and/or adaptation processes occur at the level of the peripheral organs. From among the genes assessed by microarray, up-regulation of CREB and syntaxin was confirmed by real time PCR and these two molecules were found to be immunocytochemically localized in the primary afferent neurons. Since CREB is believed to be involved in the formation of long term memory, and syntaxin is known as one of the synaptic molecules involved in the exocytosis of synaptic vesicles, the up-regulation of CREB and syntaxin may reflect synaptic plasticity occurring in the peripheral vestibular system.

Animals↗

Contractile properties and myosin expression in rats born and reared in hypergravity.

The effects of hypergravity (HG) on soleus and plantaris muscles were studied in Long Evans rats aged 100 days, born and reared in 2-g conditions (HG group). The morphological and contractile properties and the myosin heavy chain (MHC) content were examined in whole muscles and compared with terrestrial control (Cont) age-paired rats. The growth of HG rats was slowed compared with Cont rats. A decrease in absolute muscle weight was observed. An increase in fiber cross-sectional area/muscle wet weight was demonstrated, associated with an increase in relative maximal tension. The soleus muscle changed into a slower type both in contractile parameters and in MHC content, since HG soleus contained only the MHC I isoform. The HG plantaris muscle presented a faster contractile behavior. Moreover, the diversity of hybrid fiber types expressing multiple MHC isoforms (including MHC IIB and MHC IIX isoforms) was increased in plantaris muscle after HG. Thus the HG environment appears as an important inductor of muscular plasticity both in slow and fast muscle types.

Animals↗

Dispersion of 0.5- to 2-micron aerosol in microG and hypergravity as a probe of convective inhomogeneity in the lung.

We used aerosol boluses to study convective gas mixing in the lung of four healthy subjects on the ground (1 G) and during short periods of microgravity (microG) and hypergravity ( approximately 1. 6 G). Boluses of 0.5-, 1-, and 2-micron-diameter particles were inhaled at different points in an inspiration from residual volume to 1 liter above functional residual capacity. The volume of air inhaled after the bolus [the penetration volume (Vp)] ranged from 150 to 1,500 ml. Aerosol concentration and flow rate were continuously measured at the mouth. The dispersion, deposition, and position of the bolus in the expired gas were calculated from these data. For each particle size, both bolus dispersion and deposition increased with Vp and were gravity dependent, with the largest dispersion and deposition occurring for the largest G level. Whereas intrinsic particle motions (diffusion, sedimentation, inertia) did not influence dispersion at shallow depths, we found that sedimentation significantly affected dispersion in the distal part of the lung (Vp >500 ml). For 0.5-micron-diameter particles for which sedimentation velocity is low, the differences between dispersion in microG and 1 G likely reflect the differences in gravitational convective inhomogeneity of ventilation between microG and 1 G.

Adult↗

Effects of hypergravity and anti-G suit pressure on intraregional ventilation distribution during VC breaths.

The effects of increased gravity in the head-to-foot direction (+G(z)) and pressurization of an anti-G suit (AGS) on total and intraregional intra-acinar ventilation inhomogeneity were explored in 10 healthy male subjects. They performed vital capacity (VC) single-breath washin/washouts of SF(6) and He in +1, +2, or +3 G(z) in a human centrifuge, with an AGS pressurized to 0, 6, or 12 kPa. The phase III slopes for SF(6) and He over 25-75% of the expired VC were used as markers of total ventilation inhomogeneity, and the (SF(6) -- He) slopes were used as indicators of intraregional intra-acinar inhomogeneity. SF(6) and He phase III slopes increased proportionally with increasing gravity, but the (SF(6) -- He) slopes remained unchanged. AGS pressurization did not change SF(6) or He slopes significantly but resulted in increased (SF(6) -- He) slope differences at 12 kPa. In conclusion, hypergravity increases overall but not intraregional intra-acinar inhomogeneity during VC breaths. AGS pressurization provokes increased intraregional intra-acinar ventilation inhomogeneity, presumably reflecting the consequences of basilar pulmonary vessel engorgement in combination with compression of the basilar lung regions.

Adult↗

Contractile properties of rat single muscle fibers and myosin and troponin isoform expression after hypergravity.

The effects of 19 days of hypergravity (HG) were investigated on the biochemical and physiological properties of the slow soleus muscle and its fast agonist, the plantaris. HG was induced by rotational centrifugation that led to a 2-G gravity level. The HG rats were characterized by a slower body growth than control, whereas the soleus muscle mass was increased by 15%. Using electrophoretic techniques, we showed that the distribution of myosin heavy chain and troponin T isoforms was not modified after HG in both soleus and plantaris. In contrast, the isoform expression pattern of two troponin subunits, troponin I and troponin C, was changed in a slow-to-fast manner only in the soleus. From tension-pCa relationships, changes in Ca(2+) activation threshold by 0.18 pCa unit indicated a decrease in Ca(2+) sensitivity and an increase in the slope of the curve, attesting to a higher cooperativity along the thin filament after HG. Comparison of our HG data with previous results in microgravity conditions indicated that muscle characteristics, except muscle mass, did not evolve linearly from 0 to 2 G.

Animals↗

Differential changes of lung diffusing capacity and tissue volume in hypergravity.

In normal gravity, lung diffusing capacity (DL(CO)) and lung tissue volume (LTV; including pulmonary capillary blood volume) change in concert, for example, during shifts between upright and supine. Accordingly, DL(CO) and LTV might be expected to decrease together in sitting subjects in hypergravity due to peripheral pooling of blood and reduced central blood volume. Nine sitting subjects in a human centrifuge were exposed to one, two, and three times increased gravity in the head-to-feet direction (G(z+)) and rebreathed a gas containing trace amounts of acetylene and carbon monoxide. DL(CO) was 25.2 +/- 2.6, 20.0 +/- 2.1, and 16.7 +/- 1.7 ml. min(-1). mbar(-1) (means +/- SE) at 1, 2, and 3 G(z+), respectively (ANOVA P < 0.001). Corresponding values for LTV increased from 541 +/- 34 to 677 +/- 43, and 756 +/- 71 ml (P < 0.001) at 2 and 3 G(z+). Results are compatible with sequestration of blood in the dependent part of the pulmonary circulation just as in the systemic counterpart. DL(CO,) which under normoxic conditions is mainly determined by its membrane component, decreased despite an increased pulmonary capillary blood volume, most likely as a consequence of a less homogenous distribution of alveolar volume with respect to pulmonary capillary blood volume.

Adult↗

Hypergravity-induced immunomodulation in a rodent model: hematological and lymphocyte function analyses.

The major purpose of this study was to quantify hypergravity-induced changes in erythrocyte and thrombocyte characteristics, spontaneous and mitogen-induced lymphoblastogenesis, and capacity of splenocytes to secrete immunoregulatory cytokines. C57BL/6 mice were subjected to chronic 1, 2, and 3 G; subsets were euthanized after 1, 4, 7, 10, and 21 days of centrifugation. Erythrocyte counts, hematocrit, and hemoglobin were significantly reduced by day 21 in both centrifuged groups. Hemoglobin concentration and volume per red blood cell were generally low, but an early, transient spike above normal was noted in thrombocyte counts in the 3-G group. Fluctuations above and below normal in blood and spleen cell spontaneous blastogenesis were dependent on the length of centrifugation time and not on the level of gravity. Depression in splenocyte responses to phytohemagglutinin and lipopolysaccharide due to gravity were noted when the data were expressed as stimulation indexes. Cytokine production by spleen cells was primarily affected during the first week of centrifugation: IL-2, IL-4, and tumor necrosis factor-alpha increased, whereas interferon-gamma decreased. These findings, although not identical to those reported for spaceflight, indicate that altered gravity can influence both hematological and functional variables that may translate into serious health consequences during extended missions.

Animals↗