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At least 307 records · Page 17
All sourcesNASA NTRSDOE OSTI
NASA NTRS1996

Crustaceans as a model for microgravity-induced muscle atrophy

Atrophy of skeletal muscles is a serious problem in a microgravity environment. It is hypothesized that the unloading of postural muscles, which no longer must resist gravity force, causes an accelerated breakdown of contractile proteins, resulting in reduction in muscle mass and strength. A crustacean model using the land crab, Gecarcinus lateralis, to assess the effects of spaceflight on protein meatabolism is presented. The model is compared to a developmentally-regulated atrophy in which a premolt reduction in muscle mass allows the withdrawal of the large claws at molt. The biochemical mechanisms underlying protein breakdown involves both Ca2(+) -dependent and multicatalytic proteolytic enzymes. Crustacean claw muscle can be used to determine the interactions between shortening and unloading at the molecular level.

Mykles, D. L.↗
NASA NTRS1994

Interactive effects of growth hormone and exercise on muscle mass in suspended rats

Measures to attenuate muscle atrophy in rats in response to simulated microgravity (hindlimb suspension (HS)) have been only partially successful. In the present study, hypophysectomized rats were in HS for 7 days, and the effects of recombinant human growth hormone (GH), exercise (Ex), or GH+Ex on the weights, protein concentrations, and fiber cross-sectional areas (CSAs) of hindlimb muscles were determined. The weights of four extensor muscles, i.e., the soleus (Sol), medial (MG) and lateral (LG) gastrocnemius, and plantaris (Plt), and one adductor, i.e., the adductor longus (AL), were decreased by 10-22% after HS. Fiber CSAs were decreased by 34% in the Sol and by 1 17% in the MG after HS. In contrast, two flexors, i.e., the tibialis anterior (TA) and extensor digitorum longus (EDL), did not atrophy. In HS rats, GH treatment alone maintained the weights of the fast extensors (MG, LG, Plt) and flexors (TA, EDL) at or above those of control rats. This effect was not observed in the slow extensor (Sol) or AL. Exercise had no significant effect on the weight of any muscle in HS rats. A combination of GH and Ex treatments yielded a significant increase in the weights of the fast extensors and in the CSA of both fast and slow fibers of the MG and significantly increased Sol weight and CSA of the slow fibers of the Sol. The AL was not responsive to either GH or Ex treatments. Protein concentrations of the Sol and MG were higher only in the Sol of Ex and GH+Ex rats. These results suggest that while GH treatment or intermittent high intensity exercise alone have a minimal effect in maintaining the mass of unloaded muscle, there is a strong interactive effect of these two treatments.

Grindeland, Richard E.↗
NASA NTRS1995

Adaptations of human skeletal muscle fibers to spaceflight

Human skeletal muscle fibers seem to share most of the same interrelationships among myosin ATPase activity, myosin heavy chain (MHC) phenotype, mitochondrial enzyme activities, glycolytic enzyme activities, and cross-sectional area (CSA) as found in rat, cat, and other species. One difference seems to be that fast fibers with high mitochrondrial content occur less frequently in humans than in the rat or cat. Recently, we have reported that the type of MHC expressed and the size of the muscle fibers in humans that have spent 11 days in space change significantly. Specifically, about 8% more fibers express fast MHCs and all phenotypes atrophy in the vastus lateralis (VL) post compared to preflight. In the present paper we examine the relationships among the population of myonuclei, MHC type, and CSA of single human muscle fibers before and after spaceflight. These are the first data that define the relationship among the types of MHC expressed, myonuclei number, and myonuclei domain of single fibers in human muscle. We then compare these data to similar measures in the cat. In addition, the maximal torque that can be generated by the knee extensors and their fatigability before and after spaceflight are examined. These data provide some indication of the potential physiologica consequences of the muscle adaptations that occur in humans in response to spaceflight.

M. Kathleen Day↗
NASA NTRS1989

Alterations of the In Vivo Torque-Velocity Relationship of Human Skeletal Muscle Following 30 Days Exposure to Simulated Microgravity

The purpose of this study was to examine the effect of 30 d of 6 deg headdown bedrest (BR) on the in vivo strength of skeletal muscle. Peak angle specific (0.78 rad below horizontal) torque of the knee extensor (KE) and flexor (KF) muscle groups of both limbs was assessed during unilateral efforts at four speeds (0.52, 1.74, 2.97 and 4.19 rad/s) during concentric and at three speeds (0.52, 1.74 and 2.97 rad/s) during eccentric actions. The average decrease (P less than 0.05) of peak angle specific torque directly post-BR for the KE across speeds of concentric and eccentric actions was about 19% (n = 7). Recovery for 30 d following BR markedly improved strength to about 92% (P greater than 0.05) of 'normal'. Strength of the KF was not altered (P greater than 0.05) by BR (about a 6% decrease independent of speed and type of muscle action). Changes of strength were not affected by the type or speed of muscle action. The results indicate that strength of ex-tensor more than of flexor muscle groups of the lower limb is decreased by 30 d of bedrest and that this response does not alter the nature of the in vivo torque-velocity relation.

Dudley, Gary A.↗
NASA NTRS1996

Receptor Expression in Rat Skeletal Muscle Cell Cultures

One on the most persistent problems with long-term space flight is atrophy of skeletal muscles. Skeletal muscle is unique as a tissue in the body in that its ability to undergo atrophy or hypertrophy is controlled exclusively by cues from the extracellular environment. The mechanism of communication between muscle cells and their environment is through a group of membrane-bound and soluble receptors, each of which carries out unique, but often interrelated, functions. The primary receptors include acetyl choline receptors, beta-adrenergic receptors, glucocorticoid receptors, insulin receptors, growth hormone (i.e., somatotropin) receptors, insulin-like growth factor receptors, and steroid receptors. This project has been initiated to develop an integrated approach toward muscle atrophy and hypertrophy that takes into account information on the populations of the entire group of receptors (and their respective hormone concentrations), and it is hypothesized that this information can form the basis for a predictive computer model for muscle atrophy and hypertrophy. The conceptual basis for this project is illustrated in the figure below. The individual receptors are shown as membrane-bound, with the exception of the glucocorticoid receptor which is a soluble intracellular receptor. Each of these receptors has an extracellular signalling component (e.g., innervation, glucocorticoids, epinephrine, etc.), and following the interaction of the extracellular component with the receptor itself, an intracellular signal is generated. Each of these intracellular signals is unique in its own way; however, they are often interrelated.

Young, Ronald B.↗
NASA NTRS1998

Investigations of the Effects of Altered Vestibular System Function on Hindlimb Anti-Gravity Muscles

Exposure to different gravitational environments, both the microgravity of spaceflight and the hypergravity of centrifugation, result in altered vestibulo-spinal function which can be reversed by reacclimation to earth gravity (2). Control of orientation, posture, and locomotion are functions of the vestibular system which are altered by changes in gravitational environment. Not only is the vestibular system involved with coordination and proprioception, but the gravity sensing portion of the vestibular system also plays a major role in maintaining muscle tone through projections to spinal cord motoneurons that control anti-gravity muscles. I have been involved with investigations of several aspects of the link between vestibular inputs and muscle morphology and function during my work with Dr. Nancy Daunton this summer and the previous summer. We have prepared a manuscript for submission (4) to Aviation, Space, and Environmental Medicine based on work that I performed last summer in Dr. Daunton's lab. Techniques developed for that project will be utilized in subsequent experiments begun in the summer of 1998. I have been involved with the development of a pilot project to test the effects of vestibular galvanic stimulation (VGS) on anti-gravity muscles and in another project testing the effects of the ototoxic drug streptomycin on the otolith-spinal reflex and anti-gravity muscle morphology.

Lowery, Mary Sue↗
NASA NTRS1998

Variability in Beta-Adrenergic Receptor Population in Cultured Chicken Muscle Cells

Investigations into expression of the beta-adrenergic receptor (bAR) in chicken skeletal muscle cells in culture were initiated because several beta-adrenergic receptor agonists are known to increase skeletal muscle protein deposition in avian and mammalian species. During initial attempts to study the bAR population on the surface of chicken skeletal muscle cells, we observed a high degree of variability that was later found to be the result of using different batches of horse serum in the cell culture media. The separation between total binding and nonspecific binding in cells grown in two serum samples was approximately two-fold The number of nuclei within multinucleated myotubes was not significantly different in cells grown in the two serum samples. To investigate whether these two sera had an effect on coupling efficiency between bAR population and cAMP production, the ability of these cells to synthesize cAMP was also assessed. Despite the two-fold difference in receptor population, the ability of these cells to synthesize cAMP was not significantly different. Because of the possible link between bAR population and muscle protein, we also determined if the quantity of the major skeletal muscle protein, myosin, was affected by conditions that so drastically affected the bAR population. The quantity of myosin heavy chain was not significantly different.

Young, Ronald B↗
NASA NTRS2000

Effect of beta-ADrenergic Agonist on Cyclic AMP Synthesis in Chicken Skeletal Muscle Cells in Culture

Several beta-adrenergic receptor (bAR) agonists are known to cause hypertrophy of skeletal muscle tissue. Because it seems logical that these agonists exert their action on muscle through stimulation of cAMP synthesis, five bAR agonists encompassing a range in activity from strong to weak were evaluated for their ability to stimulate cAMP accumulation in embryonic chicken skeletal muscle cells in culture. Two strong agonists (epinephrine and isoproterenol), one moderate agonist (albuterol), and two weak agonists known to cause hypertrophy in animals (clenbuterol and cimaterol) were studied. Dose response curves were determined over six orders of magnitude in concentration for each agonist, and values were determined for their maximum stimulation of cAMP synthesis rate (Bmax) and the agonist concentration at which 50% stimulation of cAMP synthesis (EC50) occurred. Bmax values decreased in the following order: isoproterenol, epinephrine, albuterol, cimaterol, clenbuterol. Cimaterol and clenbuterol at their Bmax levels were approximately 15-fold weaker than isoproterenol in stimulating the rate of cAMP synthesis. In addition, the EC50 values for isoproterenol, cimaterol, clenbuterol, epinephrine, and albuterol were 360 nM, 630 nM, 900 nM, 2,470 nM, and 3,650 nM, respectively. Finally, dose response curves show that the concentrations of cimaterol and clenbuterol in culture media at concentrations known to cause significant muscle hypertrophy in animals had no detectable effect on stimulation of CAMP accumulation in chicken skeletal muscle cells.

Young, R. B.↗
NASA NTRS2000

Development of Sensory Receptors in Skeletal Muscle

There were two major goals for my project. One was to examine the hindlimb walking pattern of offspring from the Flight dams as compared with offspring of the ground control groups from initiation of walking up to two months thereafter. This initial goal was subsequently modified so that additional developmental measures were taken (e.g. body weight, eye opening) as the progeny developed, and the study period was lengthened to eighty days. Also videotapes taken shortly after the pregnant Flight dams returned to Earth were scored for locomotor activity and compared to those for the Synchronous control dams at the same stage of pregnancy. The second goal was to examine skeletal muscle. Selected hindlimb skeletal muscles were to be identified, weighed, and examined for the presence and integrity of muscle receptors, (both muscle spindles and tendon organs), at the level of the light and electron microscope. Muscles were examined from rats that were at fetal (G20), newborn (postnatal day 1 or P1, where P1 = day of birth), and young adult (approx. P100) stages. At the present time data from only the last group of rats (i.e. P100) has been completely examined.

DeSantis, Mark↗
NASA NTRS2000

Antigraviceptive neck muscle responses to "moving up and moving down" in human

The responses of neck muscle to sudden transit from one 'g' to hyper 'g', work to support the head and remain the relative position of head on trunk as common observed: i.e. in sudden acceleration or deceleration by car or ejection of pilot from aircraft. Accordingly it is highly possible that the neck muscle responses to moving up may be important to prevent the neck injury due to sudden linear acceleration such as moving up against gravity. However little is known about the evaluation of mechanism of this reflex. Therefore the present study was conducted with two aims. The first aim was to investigate the neck muscle responses to vertical linear acceleration bv 0.4 g produced with an electro-hydraulic servo-system. We chose the vertical linear acceleration because it activates mainly sacculus, from which afferents have been demonstrated to be connected directly to sternocleidomastoid muscle in animals and human. The second aim was to determine whether there is a difference of neck muscle response to moving down and moving up.

Vestibule/physiology↗
NASA NTRS2001

Role of the medial medullary reticular formation in relaying vestibular signals to the diaphragm and abdominal muscles

Changes in posture can affect the resting length of respiratory muscles, requiring alterations in the activity of these muscles if ventilation is to be unaffected. Recent studies have shown that the vestibular system contributes to altering respiratory muscle activity during movement and changes in posture. Furthermore, anatomical studies have demonstrated that many bulbospinal neurons in the medial medullary reticular formation (MRF) provide inputs to phrenic and abdominal motoneurons; because this region of the reticular formation receives substantial vestibular and other movement-related input, it seems likely that medial medullary reticulospinal neurons could adjust the activity of respiratory motoneurons during postural alterations. The objective of the present study was to determine whether functional lesions of the MRF affect inspiratory and expiratory muscle responses to activation of the vestibular system. Lidocaine or muscimol injections into the MRF produced a large increase in diaphragm and abdominal muscle responses to vestibular stimulation. These vestibulo-respiratory responses were eliminated following subsequent chemical blockade of descending pathways in the lateral medulla. However, inactivation of pathways coursing through the lateral medulla eliminated excitatory, but not inhibitory, components of vestibulo-respiratory responses. The simplest explanation for these data is that MRF neurons that receive input from the vestibular nuclei make inhibitory connections with diaphragm and abdominal motoneurons, whereas a pathway that courses laterally in the caudal medulla provides excitatory vestibular inputs to these motoneurons.

Non-NASA Center↗
NASA NTRS1994

Skeletal muscle satellite cells

Evidence now suggests that satellite cells constitute a class of myogenic cells that differ distinctly from other embryonic myoblasts. Satellite cells arise from somites and first appear as a distinct myoblast type well before birth. Satellite cells from different muscles cannot be functionally distinguished from one another and are able to provide nuclei to all fibers without regard to phenotype. Thus, it is difficult to ascribe any significant function to establishing or stabilizing fiber type, even during regeneration. Within a muscle, satellite cells exhibit marked heterogeneity with respect to their proliferative behavior. The satellite cell population on a fiber can be partitioned into those that function as stem cells and those which are readily available for fusion. Recent studies have shown that the cells are not simply spindle shaped, but are very diverse in their morphology and have multiple branches emanating from the poles of the cells. This finding is consistent with other studies indicating that the cells have the capacity for extensive migration within, and perhaps between, muscles. Complexity of cell shape usually reflects increased cytoplasmic volume and organelles including a well developed Golgi, and is usually associated with growing postnatal muscle or muscles undergoing some form of induced adaptive change or repair. The appearance of activated satellite cells suggests some function of the cells in the adaptive process through elaboration and secretion of a product. Significant advances have been made in determining the potential secretion products that satellite cells make. The manner in which satellite cell proliferative and fusion behavior is controlled has also been studied. There seems to be little doubt that cellcell coupling is not how satellite cells and myofibers communicate. Rather satellite cell regulation is through a number of potential growth factors that arise from a number of sources. Critical to the understanding of this form of control is to determine which of the many growth factors that can alter satellite cell behavior in vitro are at work in vivo. Little work has been done to determine what controls are at work after a regeneration response has been initiated. It seems likely that, after injury, growth factors are liberated through proteolytic activity and initiate an activation process whereby cells enter into a proliferative phase. After myofibers are formed, it also seems likely that satellite cell behavior is regulated through diffusible factors arising from the fibers rather than continuous control by circulating factors.(ABSTRACT TRUNCATED AT 400 WORDS).

NASA Program Space Biology↗
NASA NTRS1993

The origin of biexponential T2 relaxation in muscle water

Two theories have been proposed to explain the multiexponential transverse relaxation of muscle water protons: "anatomical" and "chemical" compartmentation. In an attempt to obtain evidence to support one or the other of these two theories, interstitial and intracellular macromolecular preparations were studied and compared with rat muscle tissue by proton NMR transverse relaxation (T2) measurements. All macromolecule preparations displayed monoexponential T2 decay. Membrane alteration with DMSO/glycerin did not eliminate the biexponential T2 decay of muscle tissue. Maceration converted biexponential T2 decay of muscle tissue to single exponential decay. It is concluded that the observed two component exponential T2 decay of muscle represents anatomical compartmentation of tissue water, probably intracellular versus extracellular.

NASA Discipline Musculoskeletal↗
NASA NTRS1992

Effects of prior exercise on the action of insulin-like growth factor I in skeletal muscle

Prior exercise increases insulin sensitivity for glucose and system A neutral amino acid transport activities in skeletal muscle. Insulin-like growth factor I (IGF-I) also activates these transport processes in resting muscle. It is not known, however, whether prior exercise increases IGF-I action in muscle. Therefore we determined the effect of a single exhausting bout of swim exercise on IGF-I-stimulated glucose transport activity [assessed by 2-deoxy-D-glucose (2-DG) uptake] and system A activity [assessed by alpha-(methylamino)isobutyric acid (MeAIB) uptake] in the isolated rat epitrochlearis muscle. When measured 3.5 h after exercise, the responses to a submaximal concentration (0.2 nM), but not a maximal concentration (13.3 nM), of insulin for activation of 2-DG uptake and MeAIB uptake were enhanced. In contrast, prior exercise increased markedly both the submaximal (5 nM) and maximal (20 nM) responses to IGF-I for activation of 2-DG uptake, whereas only the submaximal response to IGF-I (3 nM) for MeAIB uptake was enhanced after exercise. We conclude that 1) prior exercise significantly enhances the response to a submaximal concentration of IGF-I for activation of the glucose transport and system A neutral amino acid transport systems in skeletal muscle and 2) the enhanced maximal response for IGF-I action after exercise is restricted to the signaling pathway for activation of the glucose transport system.

Non-NASA Center↗
NASA NTRS1992

Role of O2 in regulating tissue respiration in dog muscle working in situ

This study was designed to investigate the role of tissue oxygenation in some of the factors that are thought to regulate muscle respiration and metabolism. Tissue oxygenation was altered by reductions in O2 delivery (muscle blood flow x arterial O2 content), induced by decreases in arterial PO2 (PaO2). O2 uptake (VO2) was measured in isolated in situ canine gastrocnemius at rest and while working at two stimulation intensities (isometric tetanic contractions at 0.5 and 1 contractions/s) on three separate occasions, with only the level of PaO2 (78, 30, and 21 Torr) being different for each occasion. Muscle blood flow was held constant (pump perfusion) at each work intensity for the three different levels of PaO2. Muscle biopsies were obtained at the end of each rest and work period. Muscle VO2 was significantly less (P less than 0.05) at both stimulation intensities for the hypoxemic conditions, whereas [ATP] was reduced only during the highest work intensity during both hypoxemic conditions (31% reduction at 21 Torr PaO2 and 17% at 30 Torr). For each level of PaO2, the relationships between the changes that occurred in VO2 and levels of phosphocreatine, ADP, and ATP/ADP.P(i) as the stimulation intensity was increased were significantly correlated; however, the slopes and intercepts of these lines were significantly different for each PaO2. Thus a greater change in any of the proposed regulators of tissue respiration (e.g., phosphocreatine, ADP) was required to achieve a given VO2 as PaO2 was decreased.(ABSTRACT TRUNCATED AT 250 WORDS).

NASA Discipline Musculoskeletal↗
NASA NTRS1992

AMP deaminase histochemical activity and immunofluorescent isozyme localization in rat skeletal muscle

The cellular distribution of AMP deaminase (AMPda) isozymes was documented for rat soleus and plantaris muscles, utilizing immunofluorescence microscopy and immunoprecipitation methods. AMPda is a ubiquitous enzyme existing as three distinct isozymes, A, B and C, which were initially purified from skeletal muscle, liver (and kidney), and heart, respectively. AMPda-A is primarily concentrated subsarcolemmally and intermyofibrillarly within muscle cells, while isozymes B and C are concentrated within non-myofiber elements of muscle tissue. AMPda-B is principally associated with connective tissues surrounding neural elements and the muscle spindle capsule, and AMPda-C is predominantly associated with circulatory elements, such as arterial and venous walls, capillary endothelium, and red blood cells. These specific localizations, combined with documented differences in kinetic properties, suggest multiple functional roles for the AMPda isozymes or temporal segregation of similar AMPda functions. Linkage of the AMPda substrate with adenosine production pathways at the AMP level and the localization of isozyme-C in vascular tissue suggest a regulatory role in the microcirculation.

Non-NASA Center↗
NASA NTRS1992

Fatigue mechanisms in patients with cancer: effects of tumor necrosis factor and exercise on skeletal muscle

Fatigue is a common adverse effect of cancer and its therapy. However, the specific mechanisms underlying cancer fatigue are unclear. One physiologic mechanism may involve changes in skeletal muscle protein stores or metabolite concentration. A reduction in skeletal muscle protein stores may result from endogenous tumor necrosis factor (TNF) or from TNF administered as antineoplastic therapy. This muscle wasting would require patients to exert an unusually high amount of effort to generate adequate contractile force during exercise performance or during extended periods of sitting or standing. This additional effort could result in the onset of fatigue. Additionally, cancer fatigue may develop or become exacerbated during exercise as a consequence of changes in the concentration of skeletal muscle metabolites. These biochemical alterations may interfere with force that is produced by the muscle contractile proteins. These physiologic changes may play a role in the decision to include exercise in the rehabilitation plans of patients with cancer. They also may affect ideas about fatigue.

Review, Tutorial↗
NASA NTRS1992

Changes in skeletal muscle gene expression consequent to altered weight bearing

Skeletal muscle is a dynamic organ that adapts to alterations in weight bearing. This brief review examines changes in muscle gene expression resulting from the removal of weight bearing by hindlimb suspension and from increased weight bearing due to eccentric exercise. Acute (less than or equal to 2 days) non-weight bearing of adult rat soleus muscle alters only the translational control of muscle gene expression, while chronic (greater than or equal to 7 days) removal of weight bearing appears to influence pretranslational, translational, and posttranslational mechanisms of control. Acute and chronic eccentric exercise are associated with alterations of translational and posttranslational control, while chronic eccentric training also alters the pretranslational control of muscle gene expression. Thus alterations in weight bearing influence multiple sites of gene regulation.

NASA Discipline Musculoskeletal↗