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PubMed2004

Effect of simulated weightlessness on osteoprogenitor cell number and proliferation in young and adult rats.

Experiments with rats flown in space or hind limb unloaded (HU) indicate that bone loss in both conditions is associated with a decrease in bone volume and osteoblast surface in cancellous and cortical bone. We hypothesize that the decrease in osteoblastic bone formation and osteoblast surface is related to a decrease in the number of osteoprogenitors and/or decreased proliferation of their progeny. We tested this hypothesis by evaluating the effect of 14 days of HU on the number of osteoprogenitors (osteoblast colony forming units; CFU-O), fibroblastic colony forming units (CFU-F), and alkaline phosphatase-positive CFU (CFU-AP) in cell populations derived from the proximal femur (unloaded) and the proximal humerus (normally loaded) in 6-week-old and 6-month-old rats. To confirm the effect of unloading on bone volume and structure, static histomorphometric parameters were measured in the proximal tibial metaphysis. Effects of HU on proliferation of osteoprogenitors were evaluated by measuring the size of CFU-O. HU did not affect the total number of progenitors (CFU-F) in young or adult rats in any of the cell populations. In femoral populations of young rats, HU decreased CFU-O by 71.0% and mean colony size was reduced by 20%. HU decreased CFU-AP by 31.3%. As expected, no changes in CFU-O or CFU-AP were seen in cell populations from the humerus. In femoral cell populations of adult rats, HU decreased CFU-O and CFU-AP by 16.6% and 36.6%, respectively. Again, no effects were seen in cell populations from the humerus. In 6-week-old rats, there was a greater decrease in bone volume, osteoblast number, and osteoblast surface in the proximal tibial metaphysis than that observed in adult rats. Both trabecular thickness and trabecular number were decreased in young rats but remained unaffected in adults. Neither osteoclast number nor surface was affected by unloading. Our results show that the HU-induced decrease in the number of osteoprogenitors observed in vitro parallels the effects of HU on bone volume and osteoblast number in young and old rats in vivo, suggesting that the two may be interdependent. HU also reduced CFU-O colony size in femoral populations indicating a diminished proliferative capacity of osteoblastic colonies.

Animals↗
PubMed1994

Neuromuscular adaptation to actual and simulated weightlessness.

The chronic "unloading" of the neuromuscular system during spaceflight has detrimental functional and morphological effects. Changes in the metabolic and mechanical properties of the musculature can be attributed largely to the loss of muscle protein and the alteration in the relative proportion of the proteins in skeletal muscle, particularly in the muscles that have an antigravity function under normal loading conditions. These adaptations could result in decrements in the performance of routine or specialized motor tasks, both of which may be critical for survival in an altered gravitational field, i.e., during spaceflight and during return to 1 G. For example, the loss in extensor muscle mass requires a higher percentage of recruitment of the motor pools for any specific motor task. Thus, a faster rate of fatigue will occur in the activated muscles. These consequences emphasize the importance of developing techniques for minimizing muscle loss during spaceflight, at least in preparation for the return to 1 G after spaceflight. New insights into the complexity and the interactive elements that contribute to the neuromuscular adaptations to space have been gained from studies of the role of exercise and/or growth factors as countermeasures of atrophy. The present chapter illustrates the inevitable interactive effects of neural and muscular systems in adapting to space. It also describes the considerable progress that has been made toward the goal of minimizing the functional impact of the stimuli that induce the neuromuscular adaptations to space.

Adaptation, Physiological↗
PubMed2000

Effects of spaceflight and simulated weightlessness on longitudinal bone growth.

Indirect measurements have suggested that spaceflight impairs bone elongation in rats. To test this possibility, our laboratory measured, by the fluorochrome labeling technique, bone elongation that occurred during a spaceflight experiment. The longitudinal growth rate (LGR) in the tibia of rats in spaceflight experiments (Physiological Space Experiments 1, 3, and 4 and Physiological-Anatomical Rodent Experiment 3) and in two models of skeletal unloading (hind-limb elevation and unilateral sciatic neurotomy) were calculated. The effects of an 11 day spaceflight on gene expression of cartilage matrix proteins in rat growth plates were also determined by northern analysis and are reported for the first time in this study. Measurements of longitudinal growth indicate that skeletal unloading generally did not affect LGR, regardless of age, strain, gender, duration of unloading, or method of unloading. There was, however, one exception with 34% suppression in LGR detected in slow-growing, ovariectomized rats skeletally unloaded for 8 days by hind-limb elevation. This detection of reduced LGR by hind-limb elevation is consistent with changes in steady-state mRNA levels for type II collagen (-33%) and for aggrecan (-53%) that were detected in rats unloaded by an 11 day spaceflight. The changes detected in gene expression raise concern that spaceflight may result in changes in the composition of extracellular matrix, which could have a negative impact on conversion of growth-plate cartilage into normal cancellous bone by endochondral ossification.

Animals↗
PubMed1990

Bone growth and calcium balance during simulated weightlessness in the rat.

Rats, age 28 days, experiencing tail suspension in modified metabolic cages for 1, 2, and 3 wk were compared with littermate controls. Food and water consumption, urinary and fecal Ca excretion, and serum Ca were measured; hearts, fore- and hindlimb bones, skulls, and mandibles were removed for determination of wet, dry, and ash weights and Ca concentration and for histological examination. Weight gain and Ca intake and excretion were the same for both groups; both displayed net Ca gain. Suspended rats had significantly lower wet, dry, and ash weights of femora and tibiae. Dry weights of the humeri and radii/ulnae were moderately higher, and the skull and mandible dry and ash weights were significantly higher in suspended than in control rats. Cortical thickness of the femur, but not humerus, was less in suspended rats. The data are consistent with the hypothesis that bone growth is influenced by the cardiovascular changes associated with tail suspension.

Animals↗
PubMed1990

Influence of single hindlimb support during simulated weightlessness in the rat.

Mature male rats (n = 16) were assigned to either 14 days of head-down suspension with one hindlimb supported (HDS) or to control cages (C) of similar dimensions. Hindlimb support during HDS preserved the muscle mass-to-body mass ratio (mg/100g) compared with C conditions for the soleus (48.3 +/- 1.0 to 41.7 +/- 1.0), plantaris (98.4 +/- 3.4 to 103.3 +/- 4.1), and gastrocnemius (484.7 +/- 18.5 to 507.2 +/- 13.9). However, the muscle mass-to-body mass ratio was significantly lower for the soleus (28.9 +/- 1.5), plantaris (83.9 +/- 3.6), and gastrocnemius (411.9 +/- 24.2) muscles from the freely hanging hindlimbs compared with the contralateral muscles from the supported hindlimbs or muscles from C animals. Citrate synthase activity (mumol.g-1.min-1) was significantly lower in soleus muscles from HDS rats in both the supported (19.4 +/- 2.3) and freely hanging (20.0 +/- 1.6) hindlimbs compared with C (28.5 +/- 3.1), whereas soleus muscle glycogen concentration (mg/g) was significantly higher in the freely hanging limbs from HDS rats (5.90 +/- 0.31) but not in the supported limbs (3.80 +/- 0.61) compared with C (4.34 +/- 0.50). Doppler flow probes were used to determine that iliac blood flow to freely hanging hindlimbs was significantly decreased after 48 (-19 +/- 5%) and 72 (-20 +/- 6%)h of HDS compared with presuspension values. In addition, iliac vascular resistance was significantly elevated at most time points during the 72 h of HDS in the freely hanging limbs but not the supported hindlimbs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

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.

Aging↗
PubMed1998

Energy and water metabolism, body composition, and hormonal changes induced by 42 days of enforced inactivity and simulated weightlessness.

Inactivity causes profound deleterious changes. We investigated in eight healthy men the impact of a 42-day head-down bed rest (HDBR) on energy and water metabolism and their interrelationships with body composition (BC) and catabolic and anabolic hormones. Total energy expenditure (TEE), total body water, water turnover, and metabolic water formation were assessed by the doubly labeled water method 15 days before and for the last 15 days of HDBR. Resting energy expenditure was determined by indirect calorimetry, and BC was determined by dual energy x-ray absorptiometry. Urinary excretion of cortisol, GH, normetanephrine, metanephrine, urea, and creatinine were measured daily. HDBR resulted in significant reductions in body weight (2%), total body water (5%), metabolic water (17%), and lean body mass (LBM; 4%), but fat mass and water turnover did not change. Segmental BC showed a decreased LBM in legs and trunk, whereas fat mass increased, no significant changes were noted in the arms. The hydration of LBM was unchanged. TEE and energy intake decreased significantly (20% and 13%), whereas resting energy expenditure was maintained. Expenditure for physical activity dropped by 39%. Subjects were in energy balance during HDBR, whereas it was negative during the control period (-1.5 MJ/day). There were decreases in urinary normetanephrine (23%) and metanephrine (23%), but urinary cortisol (28%; weeks 2 and 3), GH (75%; weeks 2-4), and urea (15%; weeks 3 and 4) increased. It was concluded that during prolonged HDBR no relevant modifications in water metabolism were triggered. BC changes occurred in the nonexercised body segments, and the reduction in TEE was due to inactivity, not to LBM loss. Moreover, body weight alone does not accurately reflect the subject's energy state, and energy balance alone could not explain the body weight loss, which involves a transient metabolic stress.

Absorptiometry, Photon↗
PubMed2002

[Orthostatic tolerance after spaceflight or simulated weightlessness by head-down bed-rest].

Cardiovascular modifications, specially orthostatic intolerance (OI) are well known after spaceflight or long duration head-down bed-rest (HDBR) There is no agreement about their mechanisms. The aim of the study was to compare OI after a 42 day HDBR (n = 7) and after a 90 to 198 day spaceflight (n = 10). The studies were made during a stand test of 10 minutes for HDBR following 10 min in supine position and 5 min in sitting position. In both groups the variables measured were blood pressure (BP by transcutaneous plethysmography, Finapres) and ECG for RR interval (RRi) determination which allowed us to calculate autonomic indexes by spectral analysis of RRi and to determine spontaneous baroreflex sensitivity. In the cosmonaut group, 1 subject experienced a vaso-vagal syncope and 2 asked to stop the test without a decrease in BP. In HDBR, 4 subjects out of 7 did not perform the whole stand test (1 vaso-vagal syncope, 1 tachycardia and 2 hypotensions). Cosmonauts or HDBR subjects had common profiles: tachycardia and a decrease in parasympathetic index and baroreflex sensitivity. Both groups have an OI (30% of the subjects). However the mechanisms are different even if they have a common postural orthostatic tachycardia syndrome (POTS). The spaceflight duration was not determinant and we have no indice to predict OI which was one of the aims of the study.

Adult↗
PubMed2002

Fluid volume changes and LBNP response after simulated weightlessness with varied oral sodium supply.

There is evidence on body fluid volume effects of head-down tilt bed rest and altered oral sodium supply, but the combined impact of both has not been investigated in detail. We therefore studied circulatory adaptation to 8 days -6 degrees head down bed rest (HDBR) with different levels (-140 to -430 mM/d) of oral sodium load (SL). We expected decreased extracellular volume and increased aldosterone and PRA levels with low sodium load, and hypothesized that these effects get exaggerated with additional HDBR, also influencing lower body suction (LBNP) responses. Variations in sodium status seem to influence plasma but not interstitial volume, confirming recent results of another group who used different experimental conditions.

Journal Article↗
PubMed2004

Brief communication: Effects of soy-protein diet on elevated brain lipid peroxide levels induced by simulated weightlessness.

The influence of soy-protein diet on brain lipid peroxidation in female rats was studied using a tail-suspension model of weightlessness. The study tested the efficacy of diets containing 0% or 11.1% soy-protein in 4 groups of female Sprague Dawley rats that were maintained with or without tail-suspension for a period of 3 weeks. At term, the whole brain was removed, segmented, and analyzed for malondialdehyde (MDA) as an index of lipid peroxidation. Brain levels of MDA were significantly higher in both tail-suspended groups than in the non-suspended control groups on the same diet, (p<0.05). The high soy-protein diet decreased MDA levels significantly, compared to the 0% soy-protein groups (p<0.05). Furthermore, MDA levels were significantly lower in the tail-suspended group on high soy-protein diet, compared to the corresponding 0% soy-protein group. In conjunction with previous findings in male rats, these data indicate that tail-suspension increases brain MDA levels in rats regardless of gender, and that a diet rich in soy-protein decreases the brain MDA level in both the non-suspended and tail-suspended groups. These observations imply that the soy-protein diet has a protective antioxidant effect during both the basal condition and the stressful condition.

Animal Feed↗