Effects Of Simulated Weightlessness Research Articles

Effects of Simulated Weightlessness on Metabolizing Enzymes and Pharmacokinetics of Folic Acid in SD Rats.

Folic acid (FA) affect human physiology and drug metabolism. Up to now, the effect of microgravity on the pharmacokinetics of FA remains unclear. The pharmacokinetics of FA in Sprague-Dawley (SD) rats are laying a foundation for safe medicine administration of astronauts. Proteins expression of such FA metabolic enzymes as Methyltetrahydrofolate reductase (MTHFR), Cystathionine beta synthase (CBS) and Methionine synthase (MS) in a variety of organs was analyzed with Western-Blot, and mRNA expression was detected by RT-PCR. The plasma concentration-time profile of FA in normal or tail-suspended SD rats was acquired by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after oral administration of FA. Area under curve (AUC) and Cmax of FA in SD rats decreased significantly with extending period of tail-suspension. In terms of expressed level of metabolic enzymes over four suspension terms, as well as the level of the corresponding mRNAs, the following regularities were found: an obvious sharp decline of MTHFR tissue in kidney, a time-dependent increase of CBS in liver tissue and duodenum tissues, the resemblance of MS fluctuation to that of CBS in tested tissues. A four-week simulated microgravity of SD rats exhibits an unequivocal diminish of bioavailability of FA, and simulated microgravity shows a varying effect on the expression of FA-metabolizing enzyme in a variety of tissues.

Effects of simulated weightlessness on thermal sweating of human body: An experimental study

Thermal sweating is the thermoregulatory activity of the human body in hot and warm environments, which is critical to the human thermal comfort and health. The sweating of a human body in a real weightlessness environment has seldom been researched, and simulated weightlessness has usually been conducted under comfortable environments. In order to study the sweating of the human body under weightlessness, a 7-day −6° head down bed rest experiment was carried out on six male subjects lying on their backs to simulate the physiological changes that occur under a weightless environment. The skin microcurrents of the subjects were recorded to evaluate sweating under a range of environments. The results showed that sweating was more significant in the torso and head areas than on the arms and lower body. The whole body sweat rates of subjects were lower than those before the simulated weightlessness experiment. However, the threshold air temperature for the onset of sweating under simulated weightlessness was higher than that before the simulation. This was possibly due to the raising of thermoregulatory set-point temperature of the body. Findings have shown that the sweating behaviour and thermal response of a male human body in a weightless environment could be different to those in the terrestrial condition.

Studies of the Effects of Simulated Weightlessness and Lunar Gravitation on the Biomechanical Parameters of Gait in Humans

We present results from a comparative analysis of the biomechanical characteristics of human gait before and after prolonged antiorthostatic hypokinesia with a body slope angle of –6° relative to the horizontal as a model of microgravitation (the ANOH group) and orthostatic hypokinesia with a positive body angle of +9.6° relative to the horizontal as model of lunar gravitation (the MOON group). Biomechanical gait characteristics were analyzed at a rate of 60 steps/min on a treadmill. Leg joint angles were measured at the hip, knee, and ankle. The electromyographic characteristics of the knee and hip muscles were also recorded. The study results showed that the most marked influences on human gait parameters were seen in subjects of the ANOH group, which was reflected in changes in the leg joint angles at different phases of stepping and changes in the electrical activity of muscles. Subjects of the MOON group showed analogous but less marked changes.

Involvement of Cholinergic Dysfunction and Oxidative Damage in the Effects of Simulated Weightlessness on Learning and Memory in Rats.

The present study aimed to determine how the learning and memory gradually change with the prolonged hindlimb unloading (HU) treatment in rats. Different HU durations (7 d, 14 d, 21 d, and 28 d) in Sprague-Dawley (SD) rats were implemented. Cognitive function was assessed using the Morris water maze (MWM) and the shuttle box test. Additionally, parameters about cholinergic activity and oxidative stress were tested. Results showed that longer-than-14 d HU led to the inferior performances in the behavioral tasks. Besides, acetylcholine esterase (AChE) activity, malondialdehyde (MDA) level in brain, reactive oxygen species (ROS), and 8-hydroxy-2-deoxyguanosine (8-OHdG) concentrations of HU rats were significantly increased. Furthermore, choline acetyltransferase (ChAT), superoxide dismutase (SOD), and catalase (CAT) activity in brain were notably attenuated. Most of these effects were more pronounced after longer exposure (21 d and 28 d) to HU, although some indicators had their own characteristics of change. These results indicate that cholinergic dysfunction and oxidative damage were involved in the learning and memory impairments induced by longer-than-14 d HU. Moreover, the negative effects of HU tend to be augmented as the HU duration becomes longer. The results may be helpful to present possible biochemical targets for countermeasures development regarding the memory deficits under extreme environmental conditions.

Effects of simulated weightlessness on biomechanics of motion unit of rhesus monkey lumbar vertebra

Effects of simulated weightlessness on biomechanics of motion unit of rhesus monkey lumbar vertebra

Production of finely graded forces in humans: effects of simulated weightlessness by water immersion

We have shown before that subjects exposed to a changed gravitoinertial environment produce exaggerated manual forces. From the observed pattern of findings, we argued that initial forces were exaggerated because of abnormal vestibular activity and peak forces because of degraded proprioceptive feedback. If so, only peak but not initial forces should be affected by water immersion, an environment that influences proprioceptive feedback but not vestibular activity. The present study was undertaken to scrutinize this prediction. Twelve subjects sat in a chair once immersed in water and once on dry land, while producing pre-trained isometric forces with a joystick. In a control experiment, subjects performed a four-choice reaction-time task. During the joystick task, produced initial forces were comparable in water and on land, while peak (+24%) and end forces (+22%) were significantly higher in water, as was their reaction time (+6%). During the control task, reaction time was comparable in water and on land. Our findings corroborate the above notion that initial forces increase when the vestibular system is stimulated (gravitoinertial change, visual field motion, but not water immersion), while peak forces increase when proprioceptive feedback is degraded (probably all three scenarios) and are not corrected until response end. Our findings further confirm the absence of cognitive slowing in simple-choice reaction tasks under shallow-water immersion conditions.

Effects of simulated weightlessness on fish otolith growth: Clinostat versus Rotating-Wall Vessel

Stimulus dependence is a general feature of developing sensory systems. It has been shown earlier that the growth of inner ear heavy stones (otoliths) of late-stage Cichlid fish ( Oreochromis mossambicus) and Zebrafish ( Danio rerio) is slowed down by hypergravity, whereas microgravity during space flight yields an opposite effect, i.e. larger than 1 g otoliths, in Swordtail ( Xiphophorus helleri) and in Cichlid fish late-stage embryos. These and related studies proposed that otolith growth is actively adjusted via a feedback mechanism to produce a test mass of the appropriate physical capacity. Using ground-based techniques to apply simulated weightlessness, long-term clinorotation (CR; exposure on a fast-rotating Clinostat with one axis of rotation) led to larger than 1 g otoliths in late-stage Cichlid fish. Larger than normal otoliths were also found in early-staged Zebrafish embryos after short-term Wall Vessel Rotation (WVR; also regarded as a method to simulate weightlessness). These results are basically in line with the results obtained on Swordtails from space flight. Thus, the growth of fish inner ear otoliths seems to be an appropriate parameter to assess the quality of “simulated weightlessness” provided by a particular simulation device. Since CR and WVR are in worldwide use to simulate weightlessness conditions on ground using small-sized specimens, we were prompted to directly compare the effects of CR and WVR on otolith growth using developing Cichlids as model organism. Animals were simultaneously subjected to CR and WVR from a point of time when otolith primordia had begun to calcify both within the utricle (gravity perception) and the saccule (hearing); the respective otoliths are the lapilli and the sagittae. Three such runs were subsequently carried out, using three different batches of fish. The runs were discontinued when the animals began to hatch. In the course of all three runs performed, CR led to larger than normal lapilli, whereas WVR had no effect on the growth of these otoliths. Regarding sagittae, CR resulted in larger than normal stones in one of the three runs. The other CR runs and all WVR runs had no effect on sagittal growth. These results clearly indicate that CR rather than WVR can be regarded as a device to simulate weightlessness using the Cichlid as model organism. Since WVR has earlier been shown to affect otolith growth in Zebrafish, the lifestyle of an animal (mouth-breeding versus egg-laying) seems to be of considerable importance. Further studies using a variety of simulation techniques (including, e.g. magnetic levitation and random positioning) and various species are needed in order to identify the most appropriate technique to simulate weightlessness regarding a particular model organism.

Effects of simulated weightlessness on tight junction protein occludin and Zonula Occluden-1 expression levels in the intestinal mucosa of rats

This study investigated the tight junction (TJ) protein expression of the intestinal mucosa in a rat tail-suspension model under simulated weightlessness. Twenty-four Wistar rats were randomly divided into three groups: CON group (n=8), control; SUS-14 d group (n=8), tail-suspension for 14 days; SUS-21 d group (n=8), tail-suspension for 21 days. Occludin and Zonula Occluden-1 (ZO-1) expression levels were determined by immunohistochemical analysis and mRNA fluorescent quantitative PCR. Plasma levels of diamine oxidase (DAO) and d-lactate were determined using enzymatic spectrophotometry. Immunohistochemical results for occludin and ZO-1 showed disruption of the TJs in the intestinal mucosa in SUS-14 d and SUS-21 d groups. The expression levels of occludin and ZO-1 in SUS-21 d group were lower than those in SUS-14 d group, and significantly lower than those in CON group (Occldin: 0.86±0.02 vs 1.01±0.03 vs 1.63±0.03 and ZO-1: 0.82±0.01 vs 1.00±0.02 vs 1.55±0.01, P<0.01). Moreover, the levels of plasma DAO and d-lactate in SUS-21 d group were higher than those in SUS-14 d group, and significantly higher than those in CON group (DAO: 27.58±0.49 vs 20.74±0.49 vs 12.94±0.21 and d-lactate: 37.86±0.74 vs 28.26±1.01 vs 17.76±0.91, P<0.01). There were significant negative correlations between occludin or ZO-1 expression levels and DAO (r (2)=0.9014, r (2)=0.9355, P<0.01) or d-lactate levels (r (2)=0.8989, r (2)=0.9331, P<0.01). Occludin and Zo-1 were reduced in intestinal mucosa both in mRNA and protein levels in the rat tail-suspension model. The significant negative correlations between expression levels of TJs and plasma levels of DAO or d-lactate support the hypothesis that intestinal permeability is increased due to a decrease in TJ protein expression during tail-suspension from 14 days to 21 days.

Effects of simulated weightlessness on liver Hsp70 and Hsp70mRNA expression in rats

Objective To investigate HspT0 expressing features of rat liver under simulated weightlessness.Methods Forty-eight male Wistar rats weighing (300±20)g were randomized into 6 experimental groups:suspended for 6 hours,12 hours,24 hours,48 hours,96 hours and 0 hours (control).Tail-suspension was used to simulate the weightlessness animal model.Hsp70 protein and its mRNA expression was then detected by using Western blot analysis and RT-PCR,respectively.Results Six and 12 hrs of the tail-suspension significantly increased Hsp70 expression at both protein and mRNA levels in rats,which persisted until 96 hours with except that Hsp70 decreased to the similar level as the control.Conclusion The simulated weightlessness acts as a kind of stress to elevate liver Hsp70 expression at both protein and mRNA levels. Key words: Genes; Hsp70; Simulated weightlessness; Rat; Liver; RT-PCR; Western blot

Effects of simulated weightlessness on apoptosis of cell line SGC-7901 and HFE-145

Effects of simulated weightlessness on apoptosis of cell line SGC-7901 and HFE-145

Energy expenditure and blood flows in thermoregulatory organs during microgravity simulation in rat. Emphasis on the importance of the control group

Rat tail suspension is commonly used to mimic human physiology in space. However, energy metabolism adaptation and related autonomic responses are unknown. To give new insights in energy homeostasis, we determined total energy expenditure (TEE) and blood flow redistribution in thermoregulatory organs during suspension using two control groups of animals widely accepted in the literature: the individually housed (isolated) and restraint rats (horizontally attached to the suspension device). Rats ( n=33) were randomly assigned during 14-days to three experimental groups: isolated, suspended, or attached. TEE was assessed by a doubly labeled water method throughout the 14 days, and regional blood flow by radiolabeled microsphere procedure at the end of the protocol. Attachment vs. suspension resulted in a significant decrease in TEE (25%), skin (54%), adrenal (55%) and kidney (42%) blood flows, cardiac index (33%), and plasma corticosterone (50%), whereas total peripheral resistances increased (50%). Isolation vs. attachment triggered an inverse response, of similar amplitude, for all above variables. By comparing isolation and suspension, no overall effect was observed. The striking conclusion of this study is that no clear conclusion can be drawn. The choice of the isolated or attached animals as control profoundly influences the outcome results regarding the effects of simulated weightlessness. Further studies are needed but we favor the attached group as the true control since, from a theoretical point of view, a suspended rat is attached plus suspended. In such conditions, TEE decreases to the same extent in rat and humans during simulated microgravity. When reviewing published experiments, we recommend special attention to the control group used rather than on the effects of suspension as compared to an undefined control.

Effects of simulated weightlessness on the migration of osteoblast precursor cells relative to blood vessels in rat periodontal ligament utilizing 3H-thymidine label : Sydney Seeauer Philadelphia, Pennsylvania: Temple University, 1989

Effects of simulated weightlessness on the migration of osteoblast precursor cells relative to blood vessels in rat periodontal ligament utilizing 3H-thymidine label : Sydney Seeauer Philadelphia, Pennsylvania: Temple University, 1989

Effects of simulated weightlessness on bone properties in rats

This paper addresses two questions: (1) are reductions in bone apposition rate during disuse due to increased periods of ‘resting’ during bone formation? and (2) are diaphyseal strength changes due to disuse caused by changes in the quality as well as the quantity of the bone matrix? These problems were studied using the tail-suspended rat model. Seventy 210 g female Sprague-Dawley rats were divided into control and suspended groups and studied for 1 or 2 weeks. Tetracycline labels at varying intervals were used to measure bone formation rates and to assess the duration of rest periods. The mechanical properties of the femoral midshaft, neck, and distal metaphysis, and of the proximal tibia, were studied. The composition of the entire femur and the geometry of the femoral midshaft were also analyzed, and beam theory was used to compare changes in these variables with those in bending strength. Contrary to previous findings in the tibia, suspension did not result in a decrease in the mean mineral apposition rate at the femur midshaft. Neither was there an effect on rest periods, so the answer to the first question was no, at least for the femur. Femur composition, cross-sectional geometry, and strength were significantly altered by disuse after 2 weeks, but not after 1 week. Femur mineralization was affected by time, but not by suspension, and bending yield stress was affected by suspension but not by time. Thus, the answer to the second question remains unclear, but is probably yes.

Effect of simulated weightlessness on the response characteristics of human brain.

In order to systematically investigate the effects of simulated weightlessness on the function state of human brain, 15 degrees head-down tilt (HDT) was used to simulate weightlessness, and the response changes of event-related EEG power spectra, medium-frequency synchronous potentials and slow-waves were examined in the present study. It was found that HDT had characteristic effects on the above EEG responses, suggesting that the effects mainly occurred in the brain's regulatory system, therefore, resulting in changes of the brain function state.

Effects of simulated weightlessness on rat osteocalcin and bone calcium.

Some of the musculoskeletal changes that occur in growing rats during spaceflight are simulated by a model that selectively unloads the hindlimbs while maintaining normal weight bearing on the forelimbs. Using this model we studied the response of mineral and the mineral-binding protein osteocalcin (OC) in the third lumbar vertebra (L3) and the femoral midshaft to periods of unweighting from 2 to 28 days. Serum OC decreased by 25%, consistent with a decreased rate of bone growth, during the first week of suspension and returned toward control values after 15 days. The L3 and femur weighed 20% less than control bones after 10-28 days. OC content of L3 and femur diaphysis were lower after 7 days of suspension and returned to normal levels at 28 days, whereas Ca content rose slightly at 5 days then decreased sharply. OC:Ca ratio was also affected. The data suggest that unweighting affects formation and deposition of OC and Ca differently depending on bone location and duration of unweighting. Both serum and bone OC are highly sensitive indicators of disruption of osteoblast activity by altered skeletal loading.

Simulated weightlessness and bone metabolism: decrease of alkaline phosphatase activity in the femoral diaphysis of rats.

The effect of simulated weightlessness on bone metabolism was investigated in the skeletal unloading for up to 9 days. The skeletal unloading was designed by using the model of hindlimb hang in rats. The food ingestion of rats with the skeletal unloading was not altered in comparison to that of normal rats. Calcium concentration in the serum was not significantly altered by the skeletal unloading for 9 days, while the serum inorganic phosphorus concentration was significantly decreased at 6 and 9 days. Calcium content in the femoral diaphysis was not altered by the skeletal unloading for 9 days. However, the activities of alkaline and acid phosphatases in the femoral diaphysis were markedly decreased by the skeletal unloading. The decrease in bone alkaline phosphatase activity was seen at 2 days with the skeletal unloading. The present results demonstrate that the skeletal unloading with hindlimb hang can induce the disorder of bone metabolism. This model is useful for studying the effects of simulated weightlessness on bone metabolism.

Effects of Simulated Weightlessness on Rabbit's Ear Microcirculation

Effects of Simulated Weightlessness on Rabbit's Ear Microcirculation

The effects of simulated weightlessness on bone biomechanical and biochemical properties in the maturing rat

Histomorphometric and biomechanical changes in bone resulting from hypogravity (simulated weightlessness) were examined in this study. Using a head-down hindlimb suspension model, three groups of six male rats underwent simulated weightlessness for periods of one, two and three weeks while a fourth recovery group was suspended for two weeks followed by two weeks of normal activity. Biomechanical data were collected during static and dynamic bending and torsion tests on intact femora. Histomorphometric values were determined from midshaft bone cross sections and material properties were obtained using ash and calcium assays. The experimental groups exhibited significantly lower geometric and material properties than the controls, resulting in structural hypotrophy; geometric and material changes contributed equally to the structural changes. Recovery following a return to normal activity was indicated, although full recovery may take longer than the weightlessness period. In the rat, altered maturation and reduced bone strength were the sequelae of weightlessness.

The effects of simulated weightlessness on bone maturation.

In earlier studies we showed that elevating the hind limbs of growing rats for up to 2 weeks results in a temporary cessation of bone growth in the hind limbs and a transient fall in the serum levels of 1,25-dihydroxyvitamin D. To determine whether such skeletal unloading also retards the maturation of bone, as seen in vitamin D-deprived animals, we fractionated by density the tibiae from rats whose hind limbs had been elevated for up to 15 days. These fractions were analyzed for dry weight, calcium content, and calcium and proline uptake. The most dense fraction (fraction 4) had the highest degree of mineralization (ratio of calcium to dry weight) and comprised 82% of the total dry weight of the control tibiae. The total incorporation of [3H]proline administered in vivo 24 h before removing the tibiae was evenly distributed among all of the fractions, although it was highest in the least dense fraction (fraction 1) when normalized to dry weight. Total incorporation of 45Ca was highest in fraction 4, although when normalized to dry weight it was highest in fraction 3. With skeletal unloading, the proportions of bone and 45Ca incorporation in fraction 4 decreased, while the proportions in less dense fractions increased. [3H]Proline incorporation fell in all fractions. These effects were maximal after 10 days of unloading and returned toward the control values after that time. We conclude that skeletal unloading transiently reduced bone formation and retarded mineralization in the growing rat, which resulted in a decrease in mature bone.

Effects of simulated weightlessness on bone mineral metabolism.

Space flight and bedrest result in a negative calcium balance and osteopenia. The mechanisms underlying these events are not well understood. In particular, it is not clear whether systemic or local factors are preeminent in mediating the effects of gravity on bone mineral content. Using a rat model that unweights only the hindlimbs, we determined whether the osteopenia induced in these rats was generalized or restricted to the unweighted limbs, and whether changes in intestinal calcium transport contributed to the alterations in bone calcium content. In this model, the hindquarters were elevated using the tail at an approximately 40 degrees angle for up to 15 days. The tibia and lumbar vertebra from experimental rats contained substantially less calcium than the same bones from pair-fed controls; at 15 days, the tibia was 86.2 +/- 2.5% of the control value (mean +/- SE), and the vertebra was 75.5 +/- 3.5% of control value (mean +/- SE). However, these differences were found only for the unweighted bones; the mandible and humerus showed no differences between experimental and pair-fed control rats. When calcium uptake by bone was evaluated after 45Ca administration, we observed an initial decrease in uptake at 5 days only in the tibia [percentage of control value, 60.5 +/- 5.5, (mean +/- SE)] and vertebra (percentage of control value, 74.3 +/- 3.7) when experimental animals were compared to pair-fed controls; there was no decrease in the humerus and mandible. However, after 10 days of unweighting , calcium uptake in the tibia and vertebra of experimental animals returned to control levels and by 15 days exceeded control levels (the tibia was 125.8 +/- 5.8% of the control value and the vertebra was 136.2 +/- 9.6% of the control value) despite the progressive decrease in total bone calcium compared to that in pair-fed controls. At no time could we demonstrate a difference in duodenal calcium transport between experimental and control animals. These data suggest that in this model, which simulates certain aspects of weightlessness, changes in local factors within the unweighted bones may have a greater impact on bone mass and turnover than changes in systemic factors that regulate overall bone mineral homeostasis.