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Stimulation of DNA polymerase alpha by hypergravity generated by centrifugal acceleration.

Gravity alteration is known to influence cell proliferation. Here we tested the effects of hypergravity on the action of DNA polymerase alpha, one of the DNA replication enzymes in eukaryotes. Hypergravity was produced by horizontal centrifugal acceleration with a hand-made rotator. The reaction rate of DNA polymerase alpha in centrifuge tubes increased along with the acceleration up to 4g, when a plateau was reached. In contrast, no stimulation was observed with primase, DNA polymerase epsilon, and the E. coli DNA polymerase I Klenow fragment. Kinetic analysis of DNA polymerase alpha reactions revealed that, under high gravity conditions, the K(m) value for template DNA decreased while the V(max) stayed constant. In contrast, the centrifugal acceleration did not affect the K(m) values for deoxyribonucleoside triphosphates. These results suggest that the hypergravity enhances the activity of DNA polymerase alpha by increasing the affinity of the enzyme for template DNA. Such enhancement was more prominent with a low concentration of DNA polymerase alpha under low ionic conditions.

Animals↗

Effects of microgravity on bone and calcium homeostasis.

Mechanical function is known to be of crucial importance for the maintenance of bone tissue. Gravity on one hand and muscular effort on the other hand are required for normal skeletal structure. It has been shown by numerous experimental studies that loss of total-body calcium, and marked skeletal changes occur in people who have flown in space. However, most of the pertinent investigations have been conducted on animal models, including rats and non-human primates, and a reasonably clear picture of bone response to spaceflight has emerged during the past few years. Osteopenia induced by microgravity was found to be associated with reduction in both cortical and trabecular bone formation, alteration in mineralization patterns and disorganization of collagen, and non-collagenous protein metabolism. Recently, cell-culture techniques have offered a direct approach of altered gravity effects at the osteoblastic-cell level. But the fundamental mechanisms by which bone and calcium are lost during spaceflight are not yet fully known. Infrequency and high financial cost of flights have created the necessity to develop on-Earth models designed to mimic weightlessness effects. Antiorthostatic suspension devices are now commonly used to obtain hindlimb unloading in rats, with skeletal effects similar to those observed after spaceflight. Therefore, actual and "simulated" spaceflights, with investigations conducted at whole body and cellular levels, are needed to elucidate pathogeny of bone loss in space, to develop effective countermeasures, and to study recovery processes of bone changes after return to Earth.

Aerospace Medicine↗

Reduced receptor aggregation and altered cytoskeleton in cultured myocytes after space-flight.

We carried out parallel experiments first on the slow clinostat and then in space-flight to examine the effects of altered gravity on the aggregation of the nicotinic acetylcholine receptors and the structure of the cytoskeleton in cultured Xenopus embryonic muscle cells. By examining the concordance between results from space flight and the clinostat, we tested whether the slow clinostat is a relevant simulation paradigm. Space-flown cells showed marked changes in the distribution and organization of actin filaments and had a reduced incidence of acetylcholine receptor aggregates at the site of contact with polystyrene beads. Similar effects were found after clinostat rotation. The sensitivity of synaptic receptor aggregation and cytoskeletal morphology suggests that in the microgravity of space cell behavior may be importantly altered.

Acetylcholine↗

Studies toward birth and early mammalian development in space.

Sustaining life beyond Earth on either space stations or other planets will require a clear understanding of how the space environment affects key phases of mammalian reproduction and development. Pregnancy, parturition (birth) and the early development of offspring are complex processes essential for successful reproduction and the proliferation of mammalian species. While no mammal has yet undergone birth within the space environment, studies spanning the gravity continuum from 0- to 2-g are revealing startling insights into how reproduction and development may proceed under gravitational conditions deviating from those typically experienced on Earth. In this report, I review studies of pregnant Norway rats and their offspring flown in microgravity onboard the NASA Space Shuttle throughout the period corresponding to mid- to late gestation, and analogous studies of pregnant rats exposed to hypergravity (hg) onboard the NASA Ames Research Center 24-ft centrifuge. Studies of postnatal rats flown in space or exposed to centrifugation are reviewed. Although many important questions remain unanswered, the available data suggest that numerous aspects of pregnancy, birth and early mammalian development can proceed under altered gravity conditions.

Animals↗

Spatial orientation of optokinetic nystagmus and ocular pursuit during orbital space flight.

On Earth, eye velocity of horizontal optokinetic nystagmus (OKN) orients to gravito-inertial acceleration (GIA), the sum of linear accelerations acting on the head and body. We determined whether adaptation to micro-gravity altered this orientation and whether ocular pursuit exhibited similar properties. Eye movements of four astronauts were recorded with three-dimensional video-oculography. Optokinetic stimuli were stripes moving horizontally, vertically, and obliquely at 30 degrees/s. Ocular pursuit was produced by a spot moving horizontally or vertically at 20 degrees/s. Subjects were either stationary or were centrifuged during OKN with 1 or 0.5 g of interaural or dorsoventral centripetal linear acceleration. Average eye position during OKN (the beating field) moved into the quick-phase direction by 10 degrees during lateral and upward field movement in all conditions. The beating field did not shift up during downward OKN on Earth, but there was a strong upward movement of the beating field (9 degrees) during downward OKN in the absence of gravity; this likely represents an adaptation to the lack of a vertical 1-g bias in-flight. The horizontal OKN velocity axis tilted 9 degrees in the roll plane toward the GIA during interaural centrifugation, both on Earth and in space. During oblique OKN, the velocity vector tilted towards the GIA in the roll plane when there was a disparity between the direction of stripe motion and the GIA, but not when the two were aligned. In contrast, dorsoventral acceleration tilted the horizontal OKN velocity vector 6 degrees in pitch away from the GIA. Roll tilts of the horizontal OKN velocity vector toward the GIA during interaural centrifugation are consistent with the orientation properties of velocity storage, but pitch tilts away from the GIA when centrifuged while supine are not. We speculate that visual suppression during OKN may have caused the velocity vector to tilt away from the GIA during dorsoventral centrifugation. Vertical OKN and ocular pursuit did not exhibit orientation toward the GIA in any condition. Static full-body roll tilts and centrifugation generating an equivalent interaural acceleration produced the same tilts in the horizontal OKN velocity before and after flight. Thus, the magnitude of tilt in OKN velocity was dependent on the magnitude of interaural linear acceleration, rather than the tilt of the GIA with regard to the head. These results favor a 'filter' model of spatial orientation in which orienting eye movements are proportional to the magnitude of low frequency interaural linear acceleration, rather than models that postulate an internal representation of gravity as the basis for spatial orientation.

Acceleration↗

Effects of gravity on the cellular response to epidermal growth factor.

EGF and related polypeptides are involved in the regulation of cell growth and differentiation of continuously regenerating tissues, in tissue repair processes and in placental and fetal development. Their initial mode of action generally constitutes binding to specific plasma membrane localized receptors, transduction of the signal across the plasma membrane, subsequent activation of signalling pathways in the cell, and the induction of early nuclear gene expression. EGF-induced signal transmission from the plasma membrane to the nucleus has been studied in microgravity in order to gain insight in the molecular mechanisms that constitute the effects of gravity on cell growth. Exposure of human A431 cells to microgravity strongly suppresses EGF- and PMA-induced c-fos and c-jun expression. In contrast, forskolin- and A23187-induced c-fos expression and constitutive beta-2 microglobulin expression remain unaffected. This suggests that microgravity differentially modulates EGF-induced signal transduction pathways. Since both EGF and PMA are known to be activators of PKC, which is not the case for forskolin and A23187, PKC-mediated signal transduction may be a cellular target for microgravity. Inhibition of EGF-induced c-fos expression by microgravity occurs downstream of the initiation of EGF-induced signal transduction, i.e., EGF binding and EGFR redistribution. In addition to PKC signaling, actin microfilament organization appears to be sensitive to microgravity. Therefore, the inhibition of signal transduction by microgravity may be related to alterations in actin microfilament organization. The fact that early gene expression is affected by agents that alter the organization of the actin microfilament system supports this hypothesis. The decrease in c-fos and c-jun expression in microgravity may result in the decreased formation of the FOS and JUN proteins. Consequently, a short-term reduction in gene expression in microgravity may have a more dramatic effect over the long term, since both the JUN and FOS protein families are required for normal cell cycle progression. However, since more than 20 years of manned spaceflight have shown that humans can survive in microgravity for prolonged periods, it appears that cells in the human body can partly or completely overcome gravitational stress. Although some insight in the molecular basis on human cells has been obtained, future studies will be needed for a better understanding of the grounds for alterations in the cellular biochemistry due to altered gravity conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Actin Cytoskeleton↗

Mitochondrial adaptations in skeletal muscle cells in mammals exposed to gravitational unloading.

It is known that exposure to actual or simulated weightlessness is often accompanied by decreased muscle dynamic performance, and increased level of blood lactate accumulation. Decreased mitochondrial content found in fibers of the working muscles is considered to be one of the possible causes for those changes. Studies on oxidative potential of the muscle cell (i.e. capacity of the cell to oxidative energy production) under conditions of altered gravity have been carried out since late 70-ties. It was shown that the relatively short term spaceflight and hindlimb suspension induced significant decrease oxidative enzyme activities and mitochondrial volume density in rat fast muscle. However postural soleus muscle failed to exhibit similar changes, although the absolute mitochondrial content was found to be sufficiently lower after exposure to simulated microgravity. This phenomenon allowed to conclude that the pronounced soleus fiber atrophy masked the proportional absolute decrease in oxidative potential which failed to be revealed as subsequent changes in mitochondrial volume density and oxidative enzyme activity. It is also important, that biosatellite studies exposed considerable changes in mitochondria distribution pattern inside m. soleus fibers: volume density of mitochondria (and, correspondingly, activity of oxidative enzymes) increases (or does not change) in the center of fiber, and decreases at its periphery, in subsarcolemmal area. However the time course of mitochondrial alterations development (particularly during long-duration exposures to real or simulated microgravity) and some peculiarities of the mitochondria distribution were not described yet. Also, materials dealing with simultaneous time-course comparative analysis of mitochondrial characteristics and indices of physiological cost of submaximal exercise are very rare. The present paper is purposed to compare the data, obtained in several experimental studies, allowed to analyze the possible contribution of muscle mitochondria changes to changes in metabolic cost of submaximal exercise and the time-course dynamics of mitochondrial characteristics under conditions of actual or simulated gravitational unloading.

Journal Article↗

Molecular developmental neurobiology of formation, guidance and survival of primary vestibular neurons.

Untangling the molecular and physiological interactions that generate the proper connections of the primary vestibular neurons in normal gravity requires two parallel approaches. One approach needs to use mutant mice to delineate the molecular basis of developmental mechanisms that govern ear development, including formation and differentiation of neurons and establishment of their peripheral and central connections. Beyond that and in addition to it, we need physiological investigations using microgravity and/or hypergravity, as well as absence of otoconia, to understand the role played by vestibular stimuli to fine tune connections of primary and secondary vestibular neurons. This paper provides an overview of some of the molecular mechanisms uncovered over the last few years that guide development, differentiation and survival of primary vestibular neurons of the mammalian ear. Briefly, several genes that are essential for primary neuron formation have been identified, all genes that govern embryonic survival are known and the first genes and mechanisms that guide formation of proper connections are being revealed. While still incomplete, the progress has been astounding and the completion of the mouse genome project will further accelerate the pace. Such data pave the way to put the research on the influence of altered gravity stimulation within a molecular framework.

Brain-Derived Neurotrophic Factor↗

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↗

Cyclic AMP-receptor responses to hypergravity.

BACKGROUND: Altered gravity (G) encountered during spaceflight causes physiologic changes in humans and in experimental animals. In addition to weightlessness (0G) in space, sharply increased G forces are exerted on the spacecraft during the lift-off and reentry phases. Previous studies showed major changes in cAMP-associated activity of rat heart muscle after spaceflight, indicating that (hormone) signaling pathways may have been affected. HYPOTHESIS: The present study was designed to test the hypothesis that cAMP-related cellular responses of exocrine glands after simulated hypergravity (centrifugation at 1.7G) differ from the effects of 0G. METHODS: A portion of the parotid and lachrymal gland tissue was fixed for morphologic and immunocytochemical study, and another was used for biochemical determinations. A short-term tissue culture was established from each gland to determine the effects of stimulation by norepinephrine. Heart muscle (ventricle) was also studied. Soluble and particulate fraction extracts of tissue homogenates were prepared, photoaffinity labeled with the [32P]8-N3-analog of cAMP, proteins separated by electrophoresis and the cAMP-reactive proteins (cARP) identified by autoradiography. RESULTS: Differences were seen in protein banding patterns of the gland extracts and in altered cARP distribution in the 1.7G samples of heart ventricle and exocrine gland tissues, when compared with 1G controls. In the heart, cARP increased in the soluble fraction, while the particulate fraction extract showed no change. In acinar cells of the parotid, labeled cARP had accumulated, but decreased after stimulation to the level of the 1G controls. Immunogold labeling showed an increased content of amylase in the secretory granules of the 1.7G animals, while morphologic observation revealed few changes in the structure of parotid acinar cells. The response in the lachrymal gland was translocation of an isoform of cARP from the particulate to the cytoplasmic compartment. CONCLUSIONS: Changes distinct from those due to 0G, but specific for hyper-G were found in cARP activity, protein synthesis, as well as in an apparent inhibition of regulated secretion.

Adaptation, Physiological↗

Behaviour of adult hamsters subjected to hypergravity.

We studied vestibular function in 20 adult hamsters (3 months old) subjected to either prolonged hypergravity (n = 10) or normal gravity (n = 10) for 2 months. Locomotion and swimming of the hypergravity hamsters under light conditions were normal. Equilibrium maintenance was severely disturbed; only 6 of 10 hypergravity hamsters managed to walk on the small tube after 2 months, whereas all 10 controls were able to walk on the tube. The air-righting reflex was severely disturbed; the hypergravity hamsters made 30% correct air-righting responses, while the control hamsters made 88% correct responses. Finally, 5 of 8 hypergravity hamsters had to be saved from drowning when swimming in total darkness. Histological examination of the utricular otoconial layers afterwards, using energy dispersive X-ray element (EDAX) analysis and scanning electron microscopy, did not reveal any differences in calcium content, shape and size distribution of the otoconia between hypergravity hamsters and controls. We suggest that adult hamsters adapt to hypergravity, leading to problems in normal functioning when tested in 1 G, especially in tasks in which sensory input of the vestibular system is important for spatial orientation. These disturbances were more severe in adult hamsters than in young ones, tested in previous experiments. Therefore, we assume that age is a factor for adaptation to altered gravity conditions.

Adaptation, Physiological↗

Changes in gravitational force cause changes in gene expression in the lens of developing zebrafish.

Gravity has been a constant physical factor during the evolution and development of life on Earth. We have been studying effects of simulated microgravity on gene expression in transgenic zebrafish embryos expressing gfp under the influence of gene-specific promoters. In this study, we assessed the effect of microgravity on the expression of the heat shock protein 70 (hsp70) gene in lens during development using transgenic zebrafish embryos expressing gfp under the control of hsp70 promoter/enhancer. Hsp70:gfp expression was up-regulated (45%) compared with controls during the developmental period that included the lens differentiation stage. This increase was lens specific, because the entire embryo showed only a 4% increase in gfp expression. Northern blot and in situ hybridization analysis indicated that the hsp70:gfp expression recapitulated endogenous hsp70 mRNA expression. Hypergravity exposure also increased hsp70 expression during the same period. In situ hybridization analysis for two lens-specific crystallin genes revealed that neither micro- nor hypergravity affected the expression level of betaB1-crystallin, a non-hsp gene used as a marker for lens differentiation. However, hypergravity changed the expression level of alphaA-crystallin, a member of the small hsp gene family. Terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling (TUNEL) assay analysis showed that altered-gravity (Deltag) decreased apoptosis in lens during the same period and the decrease correlated with the up-regulation of hsp70 expression, suggesting that elimination of nuclei from differentiating lens fiber cells was suppressed probably through hsp70 up-regulation. These results support the idea that Deltag influences hsp70 expression and differentiation in lens-specific and developmental period specific manners and that hsp family genes play a specific role in the response to Deltag.

Animals↗

Effects of static orientation upon human optokinetic afternystagmus.

"Normal" human subjects were placed in a series of 5 static orientations with respect to gravity and were asked to view an optokinetic display moving at a constant angular velocity. The axis of rotation coincided with the subject's rostro-caudal axis and produced horizontal optokinetic nystagmus and afternystagmus. Wall (1) previously reported that these optokinetic afternystagmus responses were not well characterized by parametric fits to slow component velocity. The response for nose-up, however, was larger than for nose-down. This suggested that the horizontal eye movements measured during optokinetic stimulation might include an induced linear VOR component as presented in the body of this paper. To investigate this hypothesis, another analysis of these data has been made using cumulative slow component eye position. Some subjects' responses had reversals in afternystagmus direction. These reversals were "filled in" by a zero slow component velocity. This method of analysis gives a much more consistent result across subjects and shows that, on average, responses from the nose-down horizontal (prone) orientation are greatly reduced (p < 0.05) compared to other horizontal and vertical orientations. Average responses are compared to responses predicted by a model previously used to predict successfully the responses to post-rotatory nystagmus after earth horizontal axis rotation. Ten of 11 subjects had larger responses in their supine than their prone orientation. Application of horizontal axis optokinetic afternystagmus for clinical otolith function testing, and implications for altered gravity experiments are discussed.

Gravitation↗

Mechanosensing role of caveolae and caveolar constituents in human endothelial cells.

A variety of evidence suggests that endothelial cell functions are impaired in altered gravity conditions. Nevertheless, the effects of hypergravity on endothelial cell physiology remain unclear. In this study we cultured primary human endothelial cells under mild hypergravity conditions for 24-48 h, then we evaluated the changes in cell cycle progression, caveolin1 gene expression and in the caveolae status by confocal microscopy. Moreover, we analyzed the activity of enzymes known to be resident in caveolae such as endothelial nitric oxide synthase (eNOS), cycloxygenase 2 (COX-2), and prostacyclin synthase (PGIS). Finally, we performed a three-dimensional in vitro collagen gel test to evaluate the modification of the angiogenic responses. Results indicate that hypergravity shifts endothelial cells to G(0)/G(1) phase of cell cycle, reducing S phase, increasing caveolin1 gene expression and causing an increased distribution of caveolae in the cell interior. Hypergravity also increases COX-2 expression, nitric oxide (NO) and prostacyclin (PGI2) production, and inhibits angiogenesis as evaluated by 3-D collagen gel test, through a pathway not involving apoptosis. Thus, endothelial cell caveolae may be responsible for adaptation of endothelium to hypergravity and the mechanism of adaptation involves an increased caveolin1 gene expression coupled to upregulation of vasodilators as NO and PGI2.

Adaptation, Physiological↗

Hypergravity speeds up the development of T-lymphocyte motility.

The effect of altered gravity on single cells has been reported in a number of studies. From the investigation of the immune system response to spaceflight conditions, interest has focused on the influence of gravity on single lymphocytes. Microgravity has been shown to decrease lymphocyte activation and to influence motility. On the other hand, the effect of hypergravity on lymphocyte motility has not been explored. We studied the migration of human peripheral blood T lymphocytes cultured in vitro in a hypergravity environment (10g). After hypergravity culture for 1-11 days, T cells were seeded on a fibronectin-coated glass surface, observed by time-lapse bright-field microscopy, and tracked by a computer program. We found that T cells, activated and then cultured in hypergravity, become motile earlier than cells cultured at normal gravity. These results suggest that hypergravity stimulates T cell migration.

Adaptation, Physiological↗

Energetic metabolism response in algae and higher plant species from simulation experiments with the clinostat.

Adenylate state is acknowledged to be among the most convenient approaches in the study of physiological changes in plant cells under simulation of altered gravity condition with the clinostat. Adenylate levels and the ATP/ADP ratio in cytoplasmic and mitochondrial extracts of cultivated cells of Haplopappus gracilis and algae cells of Chlorella vulgaris under initial stages of the fast-rotating and slow-rotating clinorotation, as well as the long-term clinorotation, have been investigated. For analysis of ATP and ADP levels in the plant cells under the clinorotation, we applied a high-sensitive bioluminescence method using the luciferase and piruvate kinase enzyme systems. It has been shown that the adenylate ratio is already increased during at the start of clinorotation with the different speed of rotation in the biological material tested. The considerable changes in mitochondrial ultrastructure of Chlorella cells, as well as the rising ATP level and dropping of the ATP/ADP ratio appear after long-duration clinorotation if compared to control material. It is probably connected with the distinctions in ATP-synthetase functioning in mitochondria of the cells under the clinorotation conditions.

Adenosine Diphosphate↗

On generation of statoconia in gravireceptors of mollusks.

Two models of development of statoconia in the statocyst of mollusks, based on the experimental data [Hearing Res. 49 (1990) 63; Hearing Res. 109 (1997) 125; Hearing Res. 109 (1997) 109;] are proposed. The purpose of the present work is to apply mathematical modeling to the analysis of mechanisms of statoconia formation and generation by supporting cells at the stage of their accumulation in the cyst lumen. In the case of Aplysia californica, it is not clear whether there is a temporal change of statoconia due to their growth in the cyst lumen similar to that in Biomphalaria, or whether the growth of statoconia occurs in supporting cells before they get into the cyst lumen. This question has to do with a more general and insufficiently investigated problem of the mechanisms of statoconia evolution during their stage of accumulation. This is related to A. californica as well as to the initial phase of development of Biomphalaria glabrata. This problem is of practical importance because the majority of experiments related to the study of the effects of altered gravity on the development of gravireceptors in the two mollusks A. californica and B. glabrata deals with the initial phase of statoconia development. It is assumed that two main processes determine the evolution of statoconia in developing mollusks: generation of new statoconia by growing supporting cells and growth of statoconia sizes in the cyst lumen. Analysis of experimental data related to the generation of statoconia in Aplysia and comparison of these data with the results of modeling of accumulation of statoconia suggest that the basic mechanism of evolution of size distribution of statoconia in Aplysia is growth of embryonic statoconia in supporting cells, that follows the growth of animal size. Thus, the large sizes of statoconia are determined by their development within supporting cells rather than by their growth in the cyst lumen. Analysis of the data concerning Biomphalaria allows us to assume that distribution of supporting cells which generate statoconia also varies. The results of modeling of evolution of statoconia specify necessary additional experiments, which are required to refine and test the model.

Animals↗

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↗