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At least 577 records · Page 32

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NASA NTRS1993

Absence of a growth hormone effect on rat soleus atrophy during a 4-day spaceflight

The effect of a 4-day-long spaceflight on the size and the enzyme properties of soleus fibers of rats and the effects of exogenous growth hormone (GH) on the atrophic response of the soleus muscle were investigated in four groups of rats: (1) control, (2) control plus GH treatment, (3) flight, and (4) flight plus GH treatment. Results showed that the fiber size and the type of myosin heavy chain expressed fibers (but not the metabolic properties) of the soleus were affected by four days of weightlessness and that the effects were not ameliorated by the administration of growth hormone.

Jiang, Bian↗

NASA NTRS1985

Selection of dietary protein and carbohydrate by rats: Changes with maturation

Weaning (21-day-old; 40-50 g) male rats given simultaneous access to foods, containing 18 percent casein and 15 or 70 percent carbohydrate (dextrin), tended to consume only 29-35 percent as much protein as carbohydrate (i.e., protein/carbohydrate ratios were 0.29-0.35). With maturation, when animals weighed 100 g or more, about half continued this pattern of nutrient choice, but the others abruptly began to consume considerably larger proportions of protein, exhibiting protein/carbohydrate ratios as high as 0.80-1.00. Each adult animal's protein/carbohydrate ratio tended to vary only slightly (s.e. = 3 percent of means). Adult protein/carbohydrate ratios were not correlated with fasting brain 5-HT or 5-HIAA levels. These marked differences among rats in eating behavior would not be observed when--as is usually the case--animals are given access to only one diet.

Yokogoshi, Hidehiko↗

NASA NTRS1991

Effects of systemic carbidopa on dopamine synthesis in rat hypothalamus and striatum

Significant concentrations of carbidopa (CD) were found in rat hypothalamus, striatum, and in striatal microdialysis efflux after intraperitoneal administration of the drug. Efflux levels peaked one hour after administration of 100 mg/kg at 0.37 microg/kg or about 2 percent of serum levels. Concurrent CD levels in hypothalamus and striatum were about 2.5 percent and 1.5 percent, respectively, of corresponding serum levels. Levels of dopamine and its principal metabolites in striatal efflux were unaffected. The removal of the brain blood by saline perfusion decreased the striatal and hypothalamic CD concentrations only by 33 percent and 16 percent, respectively. In other rats receiving both CD and levodopa (LD), brain L-dopa, dopamine, and 3,4-dihydroxyphenvlacetic acid (DOPAC) levels after one hour tended to be proportionate to LD dose. When the LD dose remained constant, increasing the CD dose dose-dependently enhanced L-dopa levels in the hypothalamus and striatum. However, dopamine levels did not increase but, in contrast, decreased dose-dependently (although significantly only in the hypothalamus). CD also caused dose-dependent decrease in striatal 3-O-methyldopa (3-OMD) and in striatal and hypothalamic homovanillic acid (HVA), when the LD dose was 50 mg/kg. We conclude that, at doses exceedimg 50 mg/kg, sufficient quantities of CD enter the brain to inhibit dopamine formation, especially in the hypothalamus. Moreover, high doses of LD/CD, both of which are themselves catechols, can inhibit the O-methylation of brain catecholamines formed from the LD.

Kaakkola, S.↗

NASA NTRS1988

Role of the area postrema in three putative measures of motion sickness in the rat

After thermal cauterization of the area postrema in rats, the absence of conditioned taste aversion of sucrose paired with lithium chloride (0.15M, 3.3 ml/kg) was used as a pharmacologic/behavioral index of area postrema damage. In a subsequent experiment the effects of area postrema lesions on three measures proposed as species-relevant measures of motion sickness were studied, using off-vertical rotation at 150 deg/s for either 30 or 90 min. Lesions of area postrema did not alter postrotational suppression of drinking or amount of defecation during motion. The initial acquisition of conditioned taste aversion to a novel cider vinegar solution paired with motion was not affected by lesioning of the area postrema, but these taste aversions extinguished more slowly in lesioned rats than in sham-operates or intact controls. Results are discussed in terms of proposed humoral factors which may induce motion sickness and in light of recent data on the role of the area postrema in similar measures in species possessing the complete emetic reflex.

Richard L Sutton↗

NASA NTRS1994

A metabolic cage for the hindlimb suspended rat

Hindlimb suspension has been successfully used to simulate the effects of microgravity in rats. The cage and suspension system developed by E. R. Holton is designed to produce a headward shift of fluid and unload the hindlimbs in rodents, causing changes in bone and muscle similar to those in animals and humans exposed to spaceflight. While the Holton suspension system simulates many of the conditions observed in the spaceflight animal, it does not provide for the collection of urine and feces needed to monitor some metabolic activities. As a result, only limited information has been gathered on the nutritional status, and the gastrointestinal and renal function of animals using that model. Although commercial metabolic cages are available, they are usually cylindrical and require a centrally located suspension system and thus, do not readily permit movement of the rats. The limited floor space of commercial cages may affect comparisons with studies using the Holton model which has more than twice the living space of most commercially available cages. To take advantage of the extra living space and extensive data base that has been developed with the Holton model, Holton's cage was modified to make urine and fecal collections possible.

Evans, J.↗

NASA NTRS1994

Biotelemetry implant volume and weight in rats: A pilot study report

This paper reports the results of a pilot study in which a 240-gram rat was implanted for 41 days with biotelemetry devices weighing a total of 36 gm (18 cc). The implanted animal showed no differences in weight gain, food and water consumption, and postnecropsy organ weights when compared to both an unoperated control animal and an animal that underwent surgery but did not receive an implant. The implanted animal also had temperature and activity rhythms similar to those reported using much smaller implants. Thus, this pilot study showed that a 240-gm rat could be implanted with biotelemetry devices weighing nearly 15 percent of body weight without significant changes in health or behavior. A larger study involving more animals and similar implant sizes is recommended.

Somps, Chris J.↗

NASA NTRS1993

The regulation of rat activity following exposure to hyperdynamic fields

The microgravity of space flight and the hyperdynamic fields produced via centrifugation have allowed researchers to examine the effect of altered gravitational environments on the regulation of physiological systems. In this study, a high frequency light/dark cycle was provided for 24 hours as an environmental challenge to assess the recovery of homeostatic and circadian components of physiological regulation in rats. For example, the nocturnal rat exhibited a homeostatic increase in body temperature during the dark periods and a decrease during the light periods. In addition, the magnitude of the body temperature response exhibits a time of day variation demonstrating the effect on circadian regulation.

Fuller, Charles A.↗

NASA NTRS1995

Effects of 30 day simulated microgravity and recovery on fluid homeostasis and renal function in the rat

Transition from a normal gravitational environment to that of microgravity eventually results in decreased plasma and blood volumes, increasing with duration of exposure to microgravity. This loss of vascular fluid is presumably due to negative fluid and electrolyte balance and most likely contributes to the orthostatic intolerance associated with the return to gravity. The decrease in plasma volume is presumed to be a reflection of a concurrent decrease in extracellular fluid volume with maintenance of normal plasma-interstitial fluid balance. In addition, the specific alterations in renal function contributing to these changes in fluid and electrolyte homeostasis are potentially responding to neuro-humoral signals that are not consistent with systemic fluid volume status. We have previously demonstrated an early increase in both glomerular filtration rate and extracellular fluid volume and that this decreases towards control values by 7 days of simulated microgravity. However, longer duration studies relating these changes to plasma volume alterations and the response to return to orthostasis have not been fully addressed. Male Wistar rats were chronically cannulated, submitted to 30 days heat-down tilt (HDT) and followed for 7 days after return to orthostasis from HDT. Measurements of renal function and extracellular and blood volumes were performed in the awake rat.

Tucker, Bryan J.↗

NASA NTRS1995

Mineral distribution in rat skeletons after exposure to a microgravity model

Exposure to space flight models induces changes in the distribution of bone mineral in the human skeleton that has the features of a gravitational gradient. Regional bone mineral measurements with dual energy x-ray absorptiometry (DEXA) in male adults exposed to head-down tilt bed rest for 30 days shown non-significant decrements in the pelvis and legs with 10% increases in the head region. Horizontal bed rest for 17 weeks reveals losses of bone mineral ranging from 2.2 to 10.4% from the lumbar spine to the calcaneus and an increase of 3.4% in the skull. Investigation of this phenomena would be most definitively carried out in an animal model. One candidate is the flight simulation model in the rat which removes body weight from the hind limbs and induces a cephalad fluid shift by suspending the animal by the tail. Weanling rats exposed to this model showed bone mineral to be lower in the hind limbs and higher in the skull after 3 weeks. These finds are similar in older 200 g animals after 2 weeks tail suspension. The purpose of this study was to determine the effect of age on the distribution of skeletal mineral in this model.

Arnaud, Sara B.↗

NASA NTRS1993

Anabolic Responses of an Adult Cancellous Bone Site to Prostaglandin E2 in the Rat

The objects of this study were to determine: (1) the response of a non-growing cancellous bone site to daily prostaglandin E2 (PGE2) administration; and (2) the differences in the effects of daily PGE2, administration in growing (proximal tibial metaphysis, PTM) and non-growing cancellous bone sites (distal tibial metaphysis, DTM). Seven-month-old male Sprague-Dawley rats were given daily subcutaneous injections of 0, 1, 3 and 6 mg PGE2/kg per day for 60, 120 and 180 days. The static and dynamic histomorphometric analyses were performed on double-fluorescent labeled undecalcified distal tibial metaphyses (DTM). No age-related changes were found in static and dynamic histomorphometry of DTM cancellous bone between 7 and 13 months of age. The DTM of 7-month-old (basal controls) rats consisted of a 24.5 +/- 7.61%-metaphyseal cancellous bone mass, and a thick trabeculae (92 +/- 12 micro-m). It also had a very low tissue-base bone formation rate (3.0 +/- 7.31%/year). Exogenous PGE2 administration produced the following transient changes in a dose-response manner between zero and 60 days: (1) increased trabecular bone mass and improved architecture (increased trabecular bone area, width and number, and decreased trabecular separation); (2) increased trabecular interconnections: (3) increased bone formation parameters; and (4) decreased eroded perimeter. A new steady state with more cancellous bone mass and higher bone turnover was observed from day 60 onward, The elevated bone mass induced by the first 60 days of PGE2 treatment was maintained by another 60 and 120 days with continuous daily PGE2 treatment. When these findings were compared to those previously reported for the PTM, we found that the DTM was much more responsive to PGE2 treatment than the PTM. Percent trabecular bone area and tissue based bone formation rate increased significantly more in DTM as compared to PTM after the 60 days of 6 mg PGE2 treatment. These observations indicate that a non-growing cancellous bone site is more responsive than growing bone site to long-term daily administration of PGE2.

Ito, Hiroshi↗

NASA NTRS1992

Adaptation of Cancellous Bone to Aging and Immobilization in Growing Rats

Two-and-a half month-old female rats were subjected to right hindlimb immobilization or served as controls for 0, 1, 2, 8, 14, and 20 weeks. The right hindlimb was immobilized by bandaging it against the abdomen, thus unloading it. Cancellous bone histomorphometry was performed on microradiographs and double-fluorescent labeled 20 micron sections of the distal femoral metaphyses. Primary spongiosa bone loss occurred rapidly by 2 weeks, and secondary spongiosa bone loss occurred rapidly by 8 weeks of immobilization, and then equilibrated at 60% less bone mass than age-related controls. The negative bone balance induced by immobilization was caused by transient increase in bone resorption, decrease in bone formation, and longitudinal bone growth. The dynamic data of secondary spongiosa cancellous bone showed that percent eroded perimeter was transiently elevated by 55% to 82% between 1 and 8 weeks, percent labeled perimeter was transiently depressed by 32% to 50% between 1 and 14 weeks, mineral apposition rate was depressed by 23% and 19% at 1 and 2 weeks, and bone formation rate-bone area referent was transiently depressed by 35% and 59%c at 1 and 2 weeks. All the above parameters were at age-related control levels by 20 weeks of immobilization. However, bone formation rate-tissue area referent was depressed (-65%) throughout the study. Immobilization depressed completely longitudinal bone growth by 2 weeks and remained so. Only 0.65 mm of new metaphysis was generated in the immobilized versus 2.1 mm in controls during the study period. The immobilization induced an early cancellous bone loss which equilibrated at a new steady state with less bone and a normal (age-related control) bone turnover rate. When these findings were compared to an earlier study of 9 month-old virgin females subjected to right hindlimb immobilization up to 26 weeks, we found the adaptive responses of the cancellous bone were identical except that they occurred earlier and equilibrated sooner in younger rats.

Chen, Meng Meng↗

NASA NTRS1994

Effects of Prostaglandin E2 and Risedronate Administration on Cancellous Bone in Older Female Rats

The effects of Prostaglandin E2 (PGE2) and Risedronate (Ris) both separately and in combination (PGE2 + Ris) were studied on the intact aged female rat skeleton to determine whether the combination of PGE2 with an antiresorptive agent is more effective anabolically than PGE2 alone. Nine month-old Sprague-Dawley rats were injected subcutaneously either with vehicle, 6 mg PGE2/kg per day, 1 or 5 microgram Ris/kg twice a week, or 6 mg PGE2/kg per day plus 1 or 5 microgram Ris/kg twice a week (PGE2 + 1 Ris or PGE2 + 5 Ris) for 60 days. After the treatment, we determined the longitudinal bone growth rate, the qualitative appearance of the primary spongiosa (PS), and the static and dynamic bone histomorphometry of the secondary spongiosa (SS) of the proximal tibial metaphysis (PTM) by examining undecalcified longitudinal sections after double fluorescent labeling. The relative effects of these treatments on longitudinal bone growth were ranked as follows: PGE2 + 5 Ris greater than PGE2 + 1 Ris = basal greater than PGE2 greater than 1 microgram Ris = 5 microgram Ris = aging. The density of the PS was ranked as follows: PGE2 + 5 Ris greater than PGE2 + 1 Ris = PGE2 = 5 microgram Ris = 1 microgram Ris greater than basal = aging. The increase in density of the PS was the result of stimulated longitudinal growth and the action of bisphosphonate. Bone mass in the SS was ranked as follows: PGE2 + 5 Ris = PGE2 + 1 Ris = PGE2 greater than 5 microgram Ris = 1 microgram Ris = aging = basal. However, PGE2 alone and its cotreatment with Ris accumulated bone by different tissue mechanisms. PGE2 alone created new bone by increasing activation frequency 8.3-fold and the formation to resorption ratio 1.3-fold from the controls. The combination of PGE2 and Ris depressed activation frequency (-54% to -74%), and bone formation rate (tissue-based -31%, and bone-based -42%) and eroded surface (-79% to -81%), so as to increase the formation to resorption ratio (three- to four-fold) over PGE2 alone. The increased ratio was due primarily to a greater decrease in eroded perimeter than in labeled perimeter. The major finding of this study is that the combination of PGE2 and a bisphosphonate (Ris) is more anabolic than PGE2 or Ris alone when endochondral ossification is active, but PGE2 + Ris is no more anabolic than PGE2 alone in old bone without endochondral ossification. However, the tissue mechanisms by which PGE2 alone and PGE2 + Ris treatments accumulated bone differed in that the latter allowed the same bone mass to accumulate with lower levels of cell recruitment and activity.

Lin, B. Y.↗

NASA NTRS1992

Adaptation of Cancellous Bone to Aging and Immobilization in Growing Rats

Two-and-half-month-old female rats were subjected to right hindlimb immobilization or served as controls for 0, 1, 2, 8, 14, and 20 weeks. The right hindlimb was immobilized by bandaging it against the abdomen, thus unloading it. Cancellous bone histomorphometry was performed on microradiographs and double-fluorescent labeled 20 tLm sections of the distal femoral metaphyses. Primary spongiosa bone loss occurred rapidly by 2 weeks, and secondary spongiosa bone loss occurred rapidly by 8 weeks of immobilization, and then equilibrated at 60% less bone mass than age-related controls. The negative bone balance induced by immobilization was caused by transient increase in bone resorption, decrease in bone formation, and longitudinal bone growth. The dynamic data of secondary spongiosa cancellous bone showed that percent eroded perimeter was transiently elevated by 55 to 82% between 1 and 8 weeks, percent labeled perimeter was transiently depressed by 32% to 50% between 1 and 14 weeks, mineral apposition rate was depressed by 23% and 19% at I and 2 weeks, and bone formation rate-bone area referent was transiently depressed by 35% and 59% at 1 and 2 weeks. All the above parameters were at age-related control levels by 20 weeks of immobiliza- tion. However, bone formation rate-tissue area referent was depressed (-65%) throughout the study. Immobilization depressed completely longitudinal bone growth by 2 weeks and remained so. Only 0.65 mm of new metaphysis was generated in the immobilized versus 2.1 mm in controls during the study period. The immobilization induced an early cancellous bone loss which equilibrated at a new steady state with less bone and a normal (age-related control) bone turnover rate. When these findings were compared to an earlier study of 9-month-old virgin females subjected to right hindlimb immobilization up to 26 weeks, we found the adaptive responses of the cancellous bone were identical except that they occurred earlier and equilibrated sooner in younger rats.

Chen, Meng-Meng↗

NASA NTRS1994

Metabolic Cage for a Space Flight Model in the Rat

The new cage facilitates the collection of 24-h specimens of separated urine and feces apparently uncontaminated by food, as required for precise nutritional and metabolic studies, while maintaining the large floor area and suspension method of Holton's design (3). Although the cage was evaluated, using 6-month-old rats weighing 408 to 488 g, it can be easily adjusted for smaller rats. It also was successfully used to collect post-flight urine after the recent Spacelab Life Sciences-2 space shuttle flight. With its flexibility and ease of use, this new cage design adds a new tool to study the physiologic effects of simulated space flight and other disuse conditions.

Jennifer S Harper↗

NASA NTRS1993

Morphological Changes in Rat Vestibular System Following Weightlessness

Mammalian gravity receptors (maculas) are morphologically organized for weighted, parallel distributed processing of information. There are two basic circuits: 1) highly channeled, type I cell to calyx; and 2) distributed modifying, type II cells to calyces and processes. The latter circuit should be the more adaptable since it modifies final output. To test this hypothesis, rats were flown in microgravity for 9 days aboard a space shuttle and euthanized shortly after landing. Hair cells and ribbon synapses from maculas of 3 flight and 3 ground control rats were studied ultrastructurally in blocks of 50 serial sections. Synapses increased by approximately 41% in type I cells and by approximately 55% in type II cells in flight animals. There was a shift toward the spherular form of ribbon synapse in both types of hair cells in flight animals. Current findings tend to support the stated hypothesis and indicate that mature utricular hair cells retain synaptic plasticity, permitting adaptation to an altered gravitational environment.

Ross, Muriel D.↗

NASA NTRS1984

Effect of Intracerebroventricularly Administered Octopamines and Synephrines on Angiotensin 2-Induced Water Intake in Rats

Recent studies from this laboratory showed that l-m-synephrine (phenylephrine), a metabolite of l-m-octapamine, inhibited the drinking response of rats to peripherally administered angiotensin 2. The objective of this investigation was to determine whether the isomers ofboth octapamine and synephrine could inhibit angiotensin 2-induced dipsogenesis in the rat. Of the isomers tested, only d,l-m-octopamine and l-m-synephrine blocked the dipsogenic response to administration of angiotensin 2 (200 micrograms/kg, SC). The antidipsogenic effect of both d,l-m-octopamine and l-m-synephrine could be blocked by concurrent administration of yohimbine (300 micrograms/kg, IP), an alpha(sub 2)-adrenoceptor antagonist. The results indicate that m-octopamine and m-synephrine exert their antidipsogenic effect via alpha(sub 2)-adrenoceptors. These studies add to a growing body of data suggesting that activation of alpha(sub 2)-adrenoceptors inhibits, while blockade of these receptors enhances, angiotensin 2-induced drinking.

Fregly, Melvin J.↗

NASA NTRS1984

A Role for Presynaptic alpha(sub 2)-Adrenoceptors in Angiotensin 2-Induced Drinking in Rats

Studies from this laboratory have shown that either central or peripheral administration of clonidine, the alpha(sub 2)-adrenoceptor agonist, can attenuate a variety of dipsogenic stimuli in rats. Further, yohimbine and tolazoline, alpha(sub 2)-adrenoceptor antagonists, augment the drinking response to both peripherally administered isoproterenol and angiotensin 2. Studies reported here establish a dose-inhibition relationship between the dose of clonidine administered (2 to 32 micrograms/kg) intracerebroventricularly (IVT) and inhibition of the drinking response to peripherally administered angiotensin 2 (200 micrograms/kg, SC). DI(sub 50) was approximately 4 micrograms/kg. Yohimbine (300 micrograms/kg, SC) reversed the antidipsogenic effect of centrally administered clonidine (32 micrograms/kg, IVT) on angiotensin 2-induced (200 micrograms/kg, SC) water intake. Phenylephrine, an alpha(sub 2)-adrenoceptor agonist, administered IVT (40 and 80 micrograms/kg) also inhibited angiotensin 2-induced drinking in a dose-related fashion. The antidipsogenic effect of phenylephfine (80 micrograms/kg) was blocked by administration of yohimbine (100 micrograms/kg, SC). Thus, this effect of phenylephrine most likely occurs by way of alpha(sub 2)- adrenoceptors. These results support a role for the pre-synaptic alpha(sub 2)-adrenoceptor in the mediation of drinking in rats. Activation of alpha(sub 2)-adrenoceptors is accompanied by reduced water intake while inhibition of these receptors enhances water intake.

Fregly, Melvin J.↗

NASA NTRS1996

Experimental Modification of Rat Pituitary Growth Hormone Cell Function During and After Spaceflight

Space-flown rats show a number of flight-induced changes in the structure and function of pituitary Growth Hormone (GH) cells after in vitro postflight testing. To evaluate the possible effects of microgravity on GH cells themselves, freshly dispersed rat anterior pituitary gland cells were seeded into vials containing serum +/- 1 micron HydroCortisone (HC) before flight. Five different cell preparations were used: the entire mixed-cell population of various hormone-producing cell types, cells of density less than 1.071 g/sq cm (band 1), cells of density greater than 1.071 g/sq cm (band 2), and cells prepared from either the dorsal or ventral part of the gland. Relative to ground control samples, bioactive GH released from dense cells during flight was reduced in HC-free medium but was increased in HC-containing medium. Band I and mixed cells usually showed opposite HC-dependent responses. Release of bioactive GH from ventral flight cells was lower; postflight responses to GH-releasing hormone challenge were reduced, and the cytoplasmic area occupied by GH in the dense cells was greater. Collectively, the data show that the chemistry and cellular makeup of the culture system modifies the response of GH cells to microgravity. As such, these cells offer a system to identify gravisensing mechanisms in secretory cells in future microgravity research.

Hymer, W. C.↗