Galvanic vestibular stimulation-induced activation of C1 neurons in medulla oblongata protects against acute lung injury.

Autonomic nerves, including the sympathetic and parasympathetic nerves, control the immune system along with their physiological functions. On the peripheral side, the interaction between the splenic sympathetic nerves and immune cells is important for the anti-inflammatory effects. However, the central mechanism underlying these anti-inflammatory effects remains unclear. C1 neurons respond to stressors and subsequently determine the outflow of the autonomic nervous system. We have previously shown that C1 neurons protect against acute kidney injury and found a signaling connection between peripheral vestibular organs and C1 neurons. Thus, we hypothesized that hypergravity load or galvanic vestibular stimulation (GVS) might protect against acute lung injury. We showed that C1 neurons are histologically and functionally activated by stimulating the peripheral vestibular organs. Protection against acute lung injury that was induced by a 2 G load disappeared due to vestibular lesions or the deletion of C1 neurons. This GVS-induced protective effect was also eliminated by the deletion of the C1 neurons. Furthermore, GVS increased splenic sympathetic nerve activity in conscious mice, and splenic sympathetic denervation abolished the GVS-induced protection against acute lung injury. Therefore, the activated pathway between C1 neurons and splenic sympathetic nerves is indispensable for GVS-induced protection against acute lung injury.

Repeated activation of C1 neurons in medulla oblongata decreases anti-inflammatory effect via the hypofunction of the adrenal gland adrenergic response.

The immune system is known to be controlled by the autonomic nervous system including sympathetic and parasympathetic (vagus) nerves. C1 neurons in the medulla oblongata, which participate in the control of the autonomic nervous system, are responders to stressors and regulate the immune system. Short-term activation of C1 neurons suppresses inflammation, while the effect of a long-term activation of these neurons on the inflammatory reflex is unclear. We, herein, demonstrate that the coactivation of both the splenic sympathetic nerves and the adrenal gland adrenergic response are indispensable for the prognosis of acute lung injury. The chemogenetic activation of C1 neurons increased plasma catecholamine including adrenaline and noradrenaline levels. The deletion of catecholaminergic cells using local injections of viral vector in the adrenal gland abolished the protective effect against acute lung injury when the C1 neurons were stimulated by either chemogenetic or optogenetic tools. Furthermore, repeated activation of C1 neurons using chemogenetic tool inhibited the adrenal response without affecting the plasma noradrenaline levels, eliminated the protective effect against acute lung injury. This was rescued by the isoprenaline administration. We concluded that the maintenance of an adrenergic response via C1 neurons in the adrenal gland is a prerequisite for the delivery of an effective anti-inflammatory response.

Induced genetic ablation of Rest leads to the alteration of stimulus-induced response of the vagal nerve.

Rest (RE1-silencing transcription factor, also called Nrsf) is involved in the maintenance of the undifferentiated state of neuronal stem/progenitor cells by preventing precocious expression of neuronal genes. In order to further investigate the function of Rest in neurons, we generated and examined mice evoking genetic ablation of Rest specifically in neural tissues by generating Rest conditional knockout mice. As the Rest knockout mice are embryonically lethal, we used a Sox1-Cre allele to excise the floxed Rest gene from the early stage of nerve cell differentiation including neural crest-derived nerve cells. Using this conditional Rest knockout Sox1-Cre; Restflox/flox mice, we have revealed the role of Rest in the parasympathetic nervous system in the stomach and heart.

Roles of Olfactomedin 1 in Muscle and Bone Alterations Induced by Gravity Change in Mice.

Microgravity causes both muscle and bone loss. Although we previously revealed that gravity change influences muscle and bone through the vestibular system in mice, its detailed mechanism has not been elucidated. In this study, we investigated the roles of olfactomedin 1 (OLFM1), whose expression was upregulated during hypergravity in the soleus muscle, in mouse bone cells. Vestibular lesion significantly blunted OLFM1 expression in the soleus muscle and serum OLFM1 levels enhanced by hypergravity in mice. Moreover, a phosphatidylinositol 3-kinase inhibitor antagonized shear stress-enhanced OLFM1 expression in C2C12 myotubes. As for the effects of OLFM1 on bone cells, OLFM1 inhibited osteoclast formation from mouse bone marrow cells and mouse preosteoclastic RAW264.7 cells. Moreover, OLFM1 suppressed RANKL expression and nuclear factor-κB signaling in mouse osteoblasts. Serum OLFM1 levels were positively related to OLFM1 mRNA levels in the soleus muscle and trabecular bone mineral density of mice. In conclusion, we first showed that OLFM1 suppresses osteoclast formation and RANKL expression in mouse cells.

Roles of Dkk2 in the Linkage from Muscle to Bone during Mechanical Unloading in Mice.

Mechanical unloading simultaneously induces muscle and bone loss, but its mechanisms are not fully understood. The interactions between skeletal muscle and bone have been recently noted. Although canonical wingless-related integration site (Wnt)/ß-catenin signaling is crucial for bone metabolism, its roles in the muscle and bone interactions have remained unknown. Here, we performed comprehensive DNA microarray analyses to clarify humoral factors linking muscle to bone in response to mechanical unloading and hypergravity with 3 g in mice. We identified Dickkopf (Dkk) 2, a Wnt/ß-catenin signaling inhibitor, as a gene whose expression was increased by hindlimb unloading (HU) and reduced by hypergravity in the soleus muscle of mice. HU significantly elevated serum Dkk2 levels and Dkk2 mRNA levels in the soleus muscle of mice whereas hypergravity significantly decreased those Dkk2 levels. In the simple regression analyses, serum Dkk2 levels were negatively and positively related to trabecular bone mineral density and mRNA levels of receptor activator of nuclear factor-kappa B ligand (RANKL) in the tibia of mice, respectively. Moreover, shear stress significantly suppressed Dkk2 mRNA levels in C2C12 cells, and cyclooxygenase inhibitors significantly antagonized the effects of shear stress on Dkk2 expression. On the other hand, Dkk2 suppressed the mRNA levels of osteogenic genes, alkaline phosphatase activity and mineralization, and it increased RANKL mRNA levels in mouse osteoblasts. In conclusion, we showed that muscle and serum Dkk2 levels are positively and negatively regulated during mechanical unloading and hypergravity in mice, respectively. An increase in Dkk2 expression in the skeletal muscle might contribute to disuse- and microgravity-induced bone and muscle loss.

FGF2-responsive genes in human dental pulp cells assessed using a rat spinal cord injury model.

The central nervous system in adult mammals does not heal spontaneously after spinal cord injury (SCI). However, SCI treatment has been improved recently following the development of cell transplantation therapy. We recently reported that fibroblast growth factor (FGF) 2-pretreated human dental pulp cells (hDPCs) can improve recovery in a rat model of SCI. This study aimed to investigate mechanisms underlying the curative effect of SCI enhanced via FGF2 pretreatment; we selected three hDPC lines upon screening for the presence of mesenchymal stem cell markers and of their functionality in a rat model of SCI, as assessed using the Basso, Beattie, and Bresnahan score of locomotor functional scale, electrophysiological tests, and morphological analyses. We identified FGF2-responsive genes via gene expression analyses in these lines. FGF2 treatment upregulated GABRB1, MMP1, and DRD2, which suggested to contribute to SCI or central the nervous system. In an expanded screening of additional lines, GABRB1 displayed rather unique and interesting behavior; two lines with the lowest sensitivity of GABRB1 to FGF2 treatment displayed an extremely minor effect in the SCI model. These findings provide insights into the role of FGF2-responsive genes, especially GABRB1, in recovery from SCI, using hDPCs treated with FGF2.

Role of follistatin in muscle and bone alterations induced by gravity change in mice.

Interactions between muscle and bone have been recently noted. We reported that the vestibular system plays crucial roles in the changes in muscle and bone induced by hypergravity in mice. However, the details of the mechanisms by which gravity change affects muscle and bone through the vestibular system still remain unknown. Here, we investigated the roles of humoral factors linking muscle to bone and myostatin-related factors in the hypergravity-induced changes in muscle and bone in mice with vestibular lesions (VL). Hypergravity elevated serum and mRNA levels of follistatin, an endogenous inhibitor of myostatin, in the soleus muscle of mice. VL blunted the hypergravity-enhanced levels of follistatin in the soleus muscle of mice. Simulated microgravity decreased follistatin mRNA level in mouse myoblastic C2C12 cells. Follistatin elevated the mRNA levels of myogenic genes as well as the phosphorylation of Akt and p70S6 kinase in C2C12 cells. As for bone metabolism, follistatin antagonized the mRNA levels of osteogenic genes suppressed by activin A during the differentiation of mesenchymal cells into osteoblastic cells. Moreover, follistatin attenuated osteoclast formation enhanced by myostatin in the presence of receptor activator of nuclear factor-κB ligand in RAW 264.7 cells. Serum follistatin levels were positively related to bone mass in mouse tibia. In conclusion, the present study provides novel evidence that hypergravity affects follistatin levels in muscle through the vestibular system in mice. Follistatin may play some roles in the interactions between muscle and bone metabolism in response to gravity change.

Novel roles of FKBP5 in muscle alteration induced by gravity change in mice.

Skeletal muscle hypertrophy and wasting are induced by hypergravity and microgravity, respectively. However, the mechanisms by which gravity change regulates muscle mass still remain unclear. We previously reported that hypergravity increases muscle mass via the vestibular system in mice. In this study, we performed comparative DNA microarray analysis of the soleus muscle from mice kept in 1 or 3 g environments with or without vestibular lesions. Mice were kept in 1 g or 3 g environment for 4 weeks by using a centrifuge 14 days after surgical bilateral vestibular lesions. FKBP5 was extracted as a gene whose expression was enhanced by hypergravity through the vestibular system. Stable FKBP5 overexpression increased the phosphorylations of Akt and p70 S6 kinase (muscle protein synthesis pathway) and myosin heavy chain, a myotube gene, mRNA level in mouse myoblastic C2C12 cells, although it reduced the mRNA levels of atrogin-1 and MuRF1, muscle protein degradation-related genes. In conclusion, we first showed that FKBP5 is induced by hypergravity through the vestibular system in anti-gravity muscle of mice. Our data suggest that FKBP5 might increase muscle mass through the enhancements of muscle protein synthesis and myotube differentiation as well as an inhibition of muscle protein degradation in mice.

Reduced carotid baroreceptor distensibility-induced baroreflex resetting contributes to impairment of sodium regulation in rats fed a high-fat diet.

Decreased carotid arterial compliance has been reported in obese subjects and animals. Carotid baroreceptors are located at the bifurcation of the common carotid artery, and respond to distension of the arterial wall, suggesting that higher pressure is required to obtain the same distension in obese subjects and animals. A hyperosmotic NaCl solution induces circulatory volume expansion and arterial pressure (AP) increase, which reflexively augment renal excretion. Thus, we hypothesized that sodium regulation via the baroreflex might be impaired in response to chronic hyperosmotic NaCl infusion in rats fed a high-fat diet. To examine this hypothesis, we used rats fed a high-fat (Fat) or normal (NFD) diet, and measured mean AP, water and sodium balance, and renal function in response to chronic infusion of hyperosmotic NaCl solution via a venous catheter. Furthermore, we examined arterial baroreflex characteristics with static open-loop analysis and distensibility of the common carotid artery. Significant positive water and sodium balance was observed on the 1st day of 9% NaCl infusion; however, this disappeared by the 2nd day in Fat rats. Mean AP was significantly higher during 9% NaCl infusion in Fat rats compared with NFD rats. In the open-loop analysis of carotid sinus baroreflex, a rightward shift of the neural arc was observed in Fat rats compared with NFD rats. Furthermore, distensibility of the common carotid artery was significantly reduced in Fat rats. These results indicate that a reduced baroreceptor distensibility-induced rightward shift of the neural arc might contribute to impairment of sodium regulation in Fat rats.

Hypergravity exposure for 14 days increases the effects of propofol in rats.

BACKGROUND: It is thought that the gravitational environment of space exploration alters the effects of anesthetics; however, no evidence has as yet been reported. In the present study, we sought to provide direct evidence showing that hypergravity exposure for 14 days increases anesthetic effects and to examine the possible causes. METHODS: Sprague-Dawley rats were raised in a 3g environment for 14 days. On the day of the experiment, rats were brought out of 3g and rested at 1g for 1 to 2 hours before IV propofol infusion (20 mg/kg, for 5 minutes). Control rats were continuously raised in a 1g environment. The effects of propofol were compared between rats raised in 1g and 3g environment by measuring time taken to induce the burst suppression in an electroencephalogram, nadir of arterial blood pressure, and time taken for the appearance of the righting response to noxious electrical stimulations. The time course of plasma propofol concentrations was also examined. Experiments were also conducted on rats with vestibular lesions to examine whether the vestibular system participated in the observed results. All values were expressed as mean ± SD. RESULTS: In rats raised in 3g environment, the mean time to induce burst suppression in the electroencephalogram was earlier (195.7 ± 15.1 seconds, P = 0.00037), the nadir of mean arterial blood pressure was lower (75.0 ± 15.5 mm Hg, P = 0.019), and mean time for the righting response to appear was later (39.0 ± 8.4 minutes, P < 0.0001) than in rats raised in 1g environment (267.3 ± 29.4 seconds, 100.6 ± 9.1 mm Hg, and 22.0 ± 3.1 minutes, respectively). However, mean time to induce burst suppression and for the righting response to appear did not change in rats with vestibular lesions raised in 3g environment (275 ± 29.4 seconds, 108.7 ± 14.6 mm Hg, and 20.8 ± 2.8 minutes, P = 0.95, 0.73, and 0.98 vs sham-treated rats continuously raised in a 1g environment, respectively). There was no difference between groups in the time course assessment of plasma propofol concentrations. CONCLUSION: The results provide evidence that hypergravity exposure for 14 days increases the effects of propofol. It is suggested that the results were not caused by differences in plasma propofol concentrations but by increased sensitivity, which was mediated via the vestibular system.

Remimazolam and Remifentanil Anesthetics for an Adolescent Patient with Stiff-Person Syndrome: A Case Report.

Stiff-person syndrome (SPS) is a rare autoimmune disease characterized by fluctuating rigidity and stiffness of the axial muscles. There are no reports on the use of remimazolam in a patient with SPS. A 16-year-old Japanese woman with SPS was scheduled to undergo intrathecal baclofen pump exchange. General anesthesia was induced and maintained using remimazolam, remifentanil, and intermittent rocuronium bromide. No intraoperative mobility or significant autonomic symptoms were observed. Additionally, electroencephalographic signature showed sufficient anesthetic depth. The patient's emergence from general anesthesia was uneventful. In conclusion, remimazolam could be considered an effective anesthetic drug for patients with SPS.

Aspirin augments IgE-mediated histamine release from human peripheral basophils via Syk kinase activation.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, and food additives (FAs) may exacerbate allergic symptoms in patients with chronic idiopathic urticaria and food-dependent exercise-induced anaphylaxis (FDEIA). Augmentation of histamine release from human mast cells and basophils by those substances is speculated to be the cause of exacerbated allergic symptoms. We sought to investigate the mechanism of action of aspirin on IgE-mediated histamine release. METHODS: The effects of NSAIDs, FAs or cyclooxygenase (COX) inhibitors on histamine release from human basophils concentrated by gravity separation were evaluated. RESULTS: Benzoate and tartrazine, which have no COX inhibitory activity, augmented histamine release from basophils similar to aspirin. In contrast, ibuprofen, meloxicam, FR122047 and NS-398, which have COX inhibitory activity, did not affect histamine release. These results indicate that the augmentation of histamine release by aspirin is not due to COX inhibition. It was observed that aspirin augmented histamine release from human basophils only when specifically activated by anti-IgE antibodies, but not by A23187 or formyl-methionyl-leucyl-phenylalanine. When the IgE receptor signaling pathway was activated, aspirin increased the phosphorylation of Syk. Moreover, patients with chronic urticaria and FDEIA tended to be more sensitive to aspirin as regards the augmentation of histamine release, compared with healthy controls. CONCLUSIONS: Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.

Changes in metabolism and vestibular function depend on gravitational load in mice.

The vestibular system is known to participate in controlling posture and metabolism. Different gravitational environments, including microgravity or hypergravity, cause plastic alteration of the vestibular system, and plasticity is important for adaptation to a novel gravitational environment. However, it is unclear whether the degree of change in vestibular-related physiological function depends on gravitational loading. To examine this, we used a hypergravity environment including 1.33 G, 1.67 G, and 2 G for 29 days. We found that a gravitational threshold induces physiological changes, including vestibular-related posture control and metabolism in mice. Body mass did not return to the preloading level in 1.67 G and 2 G mice. A significant drop in food intake, observed on the first day of hypergravity load, disappeared in all mice after longer exposure. However, a reduction in water intake was sustained in 2 G mice but not 1.33 G and 1.67 G mice. Body temperature did not return to the preloading level in 2 G mice by the final day. A decrease in the skill of the righting reflex was observed in 2 G mice but not 1.33 G and 1.67 G mice. In conclusion, this study showed that hypergravity-induced changes in metabolism and vestibular function depended on the amount of gravitational loading. The 2 G load affected vestibular-related posture control and metabolism considerably, compared with 1.33 G and 1.67 G loads.NEW & NOTEWORTHY It is unclear whether the degree of change in vestibular-related physiological function depends on gravitational loading. Present study showed that exposure to hypergravity-induced degrees of change in metabolism and vestibular function depended on the gravitational loading. The response of body mass depended on the gravitational loading size. Especially in 2 G environment, water intake, body temperature, and vestibular function were influenced. These changes could involve plastic alteration of vestibular-related autonomic and motor functions.

Lunar gravity prevents skeletal muscle atrophy but not myofiber type shift in mice.

Skeletal muscle is sensitive to gravitational alterations. We recently developed a multiple artificial-gravity research system (MARS), which can generate gravity ranging from microgravity to Earth gravity (1 g) in space. Using the MARS, we studied the effects of three different gravitational levels (microgravity, lunar gravity [1/6 g], and 1 g) on the skeletal muscle mass and myofiber constitution in mice. All mice survived and returned to Earth, and skeletal muscle was collected two days after landing. We observed that microgravity-induced soleus muscle atrophy was prevented by lunar gravity. However, lunar gravity failed to prevent the slow-to-fast myofiber transition in the soleus muscle in space. These results suggest that lunar gravity is enough to maintain proteostasis, but a greater gravitational force is required to prevent the myofiber type transition. Our study proposes that different gravitational thresholds may be required for skeletal muscle adaptation.

Hypergravity load-induced hyperglycemia occurs due to hypothermia and increased plasma corticosterone level in mice.

Hypothermia has been observed during hypergravity load in mice and rats. This response is beneficial for maintaining blood glucose level, although food intake decreases. However, saving glucose is not enough to maintain blood glucose level during hypergravity load. In this study, we examined the contribution of humoral factors related to glycolysis in maintaining blood glucose level in a 2 G environment. Increased plasma corticosterone levels were observed in mice with intact peripheral vestibular organs, but not in mice with vestibular lesions. Plasma glucagon levels did not change, and decrease in plasma adrenaline levels was observed in mice with intact peripheral vestibular organs. Accordingly, it is possible that increase in plasma corticosterone level and hypothermia contribute to prevent hypoglycemia in a 2 G environment.

Mn-bicine: a low affinity chelate for manganese ion enhanced MRI.

The toxicity of free Mn(2+) is a bottleneck for the in vivo application of manganese ion enhanced MRI. To reduce free Mn(2+) concentration ([Mn(2+) ]), a low affinity chelate reagent: N,N-bis(2-hydroxyethyl)glycine (bicine) was used. Considering the conditional association constant of Mn-bicine at pH 7.4 (10(2.9) M(-1) ), (i) a 100 mM Mn-bicine solution should contain about 10 mM of free manganese ion, but (ii) free manganese will make up 3/4 of the final plasma concentration (0.5 mM) with an intravenous infusion of 100 mM Mn-bicine. The T(1) relaxivity of Mn-bicine in a 5 mM Mn-bicine solution was estimated as 5 mM(-1) sec(-1) at 24°C, 7 T in a pH range of 6.8-7.5. Mn-bicine demonstrated a tendency for better contractility when employed with an isolated perfused frog heart, compared with MnCl(2) . A venous infusion of 100 mM Mn-bicine (8.3 µmol kg(-1) min(-1) ) showed a minimal decrease and maintained a constant heart rate level and arterial pressure in rats, while rats infused with 100 mM of MnCl(2) showed a significant suppression of the hemodynamic functions. Thus, Mn-bicine appears to be a better choice for maintaining the vital conditions of experimental animals, and may improve the reproducibility of manganese ion enhanced MRI.

Trial of integrated laboratory practice.

In most laboratory practices for students in medical schools, a laboratory guidebook is given to the students, in which the procedures are precisely described. The students merely follow the guidebook without thinking deeply, which spoils the students and does not entice them to think creatively. Problem-based learning (PBL) could be one means for the students themselves to actively learn, find problems, and resolve them. Such a learning attitude nurtures medical students with lifelong learning as healthcare professionals. We merged PBL and laboratory practices to promote deep thinking habits and developed an integrated laboratory practice. We gave a case sheet to groups of students from several schools. The students raised hypotheses after vivid discussion, designed experimental protocols, and performed the experiments. If the results did not support or disproved the hypothesis, the students set up another hypothesis followed by experiments, lasting for 4 or 5 consecutive days. These procedures are quite similar to those of professional researchers. The main impact achieved was the fact that the students developed the experimental design by themselves, for the first time in their college lives. All students enjoyed the laboratory practice, which they had never experienced before. This is an antidote to the guidebook-navigated traditional laboratory practice, which disappoints many students. As educators in basic medical sciences stand on the edge in terms of educating the next generation, there is a need to provide a strong foundation for medical students to design and perform scientific experiments. The integrated laboratory practice may provide the solution.

Study of mouse behavior in different gravity environments.

Many experiments have analyzed the effect of the space environment on various organisms. However, except for the group-rearing of mice in space, there has been little information on the behavior of organisms in response to gravity changes. In this study, we developed a simple Active Inactive Separation (AIS) method to extract activity and inactivity in videos obtained from the habitat cage unit of a space experiment. This method yields an activity ratio as a ratio of 'activity' within the whole. Adaptation to different gravitational conditions from 1g to hypergravity (HG) and from microgravity (MG) to artificial 1g (AG) was analyzed based on the amount of activity to calculate the activity ratio and the active interval. The result for the activity ratios for the ground control experiment using AIS were close to previous studies, so the effectiveness of this method was indicated. In the case of changes in gravity from 1g to HG, the ratio was low at the start of centrifugation, recovered sharply in the first week, and entered a stable period in another week. The trend in the AG and HG was the same; adapting to different gravity environments takes time.

Development and evaluation of gas-pressurized elastic sleeves for extravehicular activity.

INTRODUCTION: In space, mobility of the current extravehicular activity space suit is limited due to the pressure differential between the inside and outside of the suit. We have previously demonstrated that an elastic glove increased mobility when compared with a non-elastic glove such as that found in the current suit. Extending this work, we hypothesized that an elastic sleeve would also have more mobility compared to a non-elastic sleeve, but a partially elastic sleeve, consisting of elastic joints sewn to non-elastic parts in low mobility areas, might generate similar mobility to a wholly elastic sleeve. METHODS: The right arms of 10 volunteers were studied with wholly elastic, partially elastic, and non-elastic sleeves in a chamber pressure of -220 mmHg. Range of motion (ROM) of the wrist and electromyography (EMG) of the flexor carpi radialis muscle and the biceps brachii muscle during wrist and elbow flexion were measured. RESULTS: ROM of the wrist was similar among all the sleeves. However, EMG amplitudes during wrist flexion with both elastic sleeves were significantly smaller than that with the non-elastic sleeve. EMG amplitudes during 90 degrees of elbow flexion were also significantly smaller in both elastic sleeves. However, no significant difference in EMG amplitudes was observed between the two elastic sleeves (0.53 +/- 0.06, 0.56 +/- 0.07, 1.14 +/- 0.10 V for wholly elastic, partially elastic, and non-elastic sleeves, respectively). DISCUSSION: The mobility of elastic sleeves is better than that of a non-elastic sleeve. Elasticity over the joints is important; however the elasticity of the other parts does not appear to affect mobility.

Understanding vestibular-related physiological functions could provide clues on adapting to a new gravitational environment.

The peripheral vestibular organs are sensors for linear acceleration (gravity and head tilt) and rotation. Further, they regulate various body functions, including body stability, ocular movement, autonomic nerve activity, arterial pressure, body temperature, and muscle and bone metabolism. The gravitational environment influences these functions given the highly plastic responsiveness of the vestibular system. This review demonstrates that hypergravity or microgravity induces changes in vestibular-related physiological functions, including arterial pressure, muscle and bone metabolism, feeding behavior, and body temperature. Hopefully, this review contributes to understanding how human beings can adapt to a new gravitational environment, including the moon and Mars, in future.