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At least 37 records · Page 2

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NASA NTRS1997

Interaction of thyroid state and denervation on skeletal myosin heavy chain expression

The goal of this study was to examine the effects of altered thyroid state and denervation (Den) on skeletal myosin heavy chain (MHC) expression in the plantaris and soleus muscles. Rats were subjected to unilateral denervation (Den) and randomly assigned to one of three groups: (1) euthyroid; (2) hyperthyroid; (3) and hypothyroid. Denervation caused severe muscle atrophy and muscle-type specific MHC transformation. Denervation transformed the soleus to a faster muscle, and its effects required the presence of circulating thyroid hormone. In contrast, denervation transformed the plantaris to a slower muscle independently of thyroid state. Furthermore, thyroid hormone effects did not depend upon innervation status in the soleus, while they required the presence of the nerve in the plantaris. Collectively, these findings suggest that both thyroid hormone and intact nerve (a) differentially affect MHC transformations in fast and slow muscle; and (b) are important factors in regulating the optimal expression of both type I and IIB MHC genes. This research suggests that for patients with nerve damage and/or paralysis, both muscle mass and biochemical properties can also be affected by the thyroid state.

NASA Discipline Musculoskeletal↗

NASA NTRS1995

Adaptive responses of GLUT-4 and citrate synthase in fast-twitch muscle of voluntary running rats

Glucose transporter (GLUT-4) protein, hexokinase, and citrate synthase (proteins involved in oxidative energy production from blood glucose catabolism) increase in response to chronically elevated neuromuscular activity. It is currently unclear whether these proteins increase in a coordinated manner in response to this stimulus. Therefore, voluntary wheel running (WR) was used to chronically overload the fast-twitch rat plantaris muscle and the myocardium, and the early time courses of adaptative responses of GLUT-4 protein and the activities of hexokinase and citrate synthase were characterized and compared. Plantaris hexokinase activity increased 51% after just 1 wk of WR, whereas GLUT-4 and citrate synthase were increased by 51 and 40%, respectively, only after 2 wk of WR. All three variables remained comparably elevated (+50-64%) through 4 wk of WR. Despite the overload of the myocardium with this protocol, no substantial elevations in these variables were observed. These findings are consistent with a coordinated upregulation of GLUT-4 and citrate synthase in the fast-twitch plantaris, but not in the myocardium, in response to this increased neuromuscular activity. Regulation of hexokinase in fast-twitch muscle appears to be uncoupled from regulation of GLUT-4 and citrate synthase, as increases in the former are detectable well before increases in the latter.

Non-NASA Center↗

NASA NTRS1980

Effects of chronic centrifugation on skeletal muscle fibers in young developing rats

Three groups of 30-d old male and female rats were centrifuged for 2, 4, 8, and 16 weeks, after which their soleus and plantaris muscles were analysed for changes in proportions of muscle fiber types. The groups were: earth control, maintained at earth gravity without rotation; rotation control, subjected to a gravitational force of 1.05 G and 28 rpm; and rotation experimental, subjected to a gravitational force of 2 G and 28 rpm. Muscle fibers were classified into four fiber types on the basis of actomyosin ATPase activity as slow oxidative, fast oxidative glycolytic and either fast glycolytic (plantaris) or intermediate (soleus). Hypergravity resulted in an increase in slow oxidative fibers in soleus relative to the earth control, but not of females treated similarly. The relationship of body weight to the changes in proportion of slow oxidative fibers is discussed.

Martin, W. D.↗

NASA NTRS1983

Rat hindlimb muscle responses to suspension hypokinesia/hypodynamia

Hypokinetic/hyupodynamic (H/H) whole body suspension of rats eliminates hindlimb load bearing functions while permitting continued use of the forelimbs. Responses of hindlimb muscles were assessed in terms of absolute and relative weights during 1 and 2 weeks of H/H suspension. Muscle mass loss was in the order soleus greater than gastrocnemius equal to plantaris greater than extensor digitorum longus (EDL). The soleus, a postural antigravity muscle composed mainly of slow twitch fibers, was most sensitive, losing 35 and 45 percent of its weight during the first and second weeks, respectively. The gastrocnemius and plantaris showed losses during the first week but no significant loss during the second wee. The EDL showed little or no weight loss. During post suspension recovery all muscles showed a weight gain. H/H suspended rats failed to grow; following removal from suspension they gained weight linearly, comparable to controls. Products of muscle metabolism including urea, ammonia, and 3-methylhistidine increased in the urine during H/H suspension and were significantly reduced approaching control levels during recovery. This suspension model offers considerable promise for comparison with H/H responses during weightlessness.

Musacchia, X. J.↗

NASA NTRS1984

No effect of sex steroids on compensatory muscle hypertrophy

The effects of orchiectomy and/or subcutaneously implanted testosterone propionate (TP) on the hypertrophic response of rat plantaris muscles to functional overload (induced by bilateral removal of gastrocnemius and soleus muscles) are investigated experimentally. Muscle wet weight, metabolic substrate oxidation, and cytosolic androgen-receptor binding are measured, and the results are presented in tables. Eight weeks after surgery, the plantaris muscle weight as a percentage of body weight is found to be about twice that in rats without muscle overload, regardless of the sex-hormone status. Overloading causes decreased ability to oxidize glucose and pyruvate, decreased succinate dehydrogenase specific activity, and no change in the ability to oxidize beta-hydroxybutyrate or in androgen-receptor binding. The oxidative response is unaffected by orchiectomy or TP or both. It is argued that the actions of sex hormones and functional overload are not synergistic.

Max, S. R.↗

NASA NTRS1986

Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles

The regulation of glutamine synthetase by glucocorticoids in rat skeletal muscles was studied. Administration of dexamethasone strikingly enhanced glutamine synthetase activity in plantaris and soleus muscles. The dexamethasone-mediated induction of glutamine synthetase activity was blocked to a significant extent by orally administered RU38486, a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves dramatically increased levels of glutamine synthetase mRNA. The induction of glutamine synthetase was selective in that glutaminase activity of soleus and plantaris muscles was not increased by dexamethasone. Furthermore, dexamethasone treatment resulted in only a small increase in glutamine synthetase activity in the heart. Accordingly, there was only a slight change in glutamine synthetase mRNA level in this tissue. Thus, glucocorticoids regulate glutamine synthetase gene expression in rat muscles at the transcriptional level via interaction with intracellular glutamine production by muscle and to mechanisms underlying glucocorticoid-induced muscle atrophy.

Max, Stephen R.↗

NASA NTRS1988

Problems in analysis of data from muscles of rats flow in space

Comparison of hind-limb muscles of rats flown on Spacelab-3 or tail-traction-suspended showed that 11-17 h reloading postflight might have altered the results. Soleus atrophied; plantaris, gastrocnemius, and extensor digitorum longus grew slower; and tibialis anteiror grew normally. In both flight and simulated soleus and plantaris, higher tyrosine and greater glutamine/glutamate ratio indicated negative protein balance and increased glutamine production, respectively, relative to controls. Aspartate was lower in these muscles. Reloading generally decreased tyrosine, but increased aspartate and glutamine/glutamate. These data showed that 12 h of reloading after flight is characterized by reversal, to varying extents, of the effects of unloading.

Tischler, Marc E.↗

NASA NTRS1988

Effects of immobilization on rat hind limb muscles under non-weight-bearing conditions

The effect of stretched and unstretched immobilization of a hind limb on the concentration and the metabolism of proteins in the hind-limb muscles of rats was investigated. The animals were divided into three groups: (1) weight-bearing controls, (2) tail-cast-suspended, and (3) suspended, with one hind limb immobilized with the ankle in dorsiflexion (30-40 deg angle) and the other freely moving. It was found that unloading the hind limbs for 6 days by tail cast suspension caused soleus to atrophy and reduced growth of the gastrocnemius and plantaris muscles; unloading resulted in a higher degradation rate and lower synthesis rate in both in vitro and in vivo. Chronic stretch of the unloaded soleus not only prevented its atrophy but led to significant hypertrophy, relative to weight-bearing controls, with increases in both the sarcoplasmic and myofibrillar protein fractions. Immobilizing one ankle in dorsiflexion prevented the inhibition of growth in the plantaris and gastrocnemius muscles due to unloading.

Jaspers, Stephen R.↗

NASA NTRS2002

Gravitational unloading effects on muscle fiber size, phenotype and myonuclear number

The effects of gravitational unloading with or without intact neural activity and/or tension development on myosin heavy chain (MHC) composition, cross-sectional area (CSA), number of myonuclei, and myonuclear domain (cytoplasmic volume per myonucleus ratio) in single fibers of both slow and fast muscles of rat hindlimbs are reviewed briefly. The atrophic response to unloading is generally graded as follows: slow extensors > fast extensors > fast flexors. Reduction of CSA is usually greater in the most predominant fiber type of that muscle. The percentage of fibers expressing fast MHC isoforms increases in unloaded slow but not fast muscles. Myonuclear number per mm of fiber length and myonuclear domain is decreased in the fibers of the unloaded predominantly slow soleus muscle, but not in the predominantly fast plantaris. Decreases in myonuclear number and domain, however, are observed in plantaris fibers when tenotomy, denervation, or both are combined with hindlimb unloading. All of these results are consistent with the view that a major factor for fiber atrophy is an inhibition or reduction of loading of the hindlimbs. These data also indicate that predominantly slow muscles are more responsive to unloading than predominantly fast muscles. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Review, Tutorial↗

NASA NTRS2001

Time course of the MAPK and PI3-kinase response within 24 h of skeletal muscle overload

Knowledge of the molecular mechanisms by which skeletal muscle hypertrophies in response to increased mechanical loading may lead to the discovery of novel treatment strategies for muscle wasting and frailty. To gain insight into potential early signaling mechanisms associated with skeletal muscle hypertrophy, the temporal pattern of mitogen-activated protein kinase (MAPK) phosphorylation and phosphatidylinositol 3-kinase (PI3-kinase) activity during the first 24 h of muscle overload was determined in the rat slow-twitch soleus and fast-twitch plantaris muscles after ablation of the gastrocnemius muscle. p38alpha MAPK phosphorylation was elevated for the entire 24-h overload period in both muscles. In contrast, Erk 2 and p54 JNK phosphorylation were transiently increased by overload, returning to the levels of sham-operated controls by 24 h. PI3-kinase activity was increased by muscle overload only at 12 h of overload and only in the plantaris muscle. In summary, sustained elevation of p38alpha MAPK phosphorylation occurred early in response to muscle overload, identifying this pathway as a potential candidate for mediating early hypertrophic signals in response to skeletal muscle overload.

Non-NASA Center↗

NASA NTRS1988

Problems in analysis of data from muscles of rats flown in space

Comparison of hindlimb muscles of rats flown on Spacelab-3 or tail-traction-suspended showed that 11-17 h reloading post-flight might have altered the results. Soleus atrophied, plantaris, gastrocnemius and extensor digitorum longus grew slower, and tibialis anterior grew normally. In both flight and simulated soleus and plantaris, higher tyrosine and greater glutamine/glutamate ratio indicated negative protein balance and increased glutamine production, respectively, relative to controls. Aspartate was lower in these muscles. Reloading generally decreased tyrosine, but increased aspartate and glutamine/glutamate. These data showed that at 12 h of reloading after flight is characterized by reversal to varying extents of effects of unloading.

Non-NASA Center↗

NASA NTRS2000

Single-fiber myosin heavy chain polymorphism during postnatal development: modulation by hypothyroidism

The primary objective of this study was to follow the developmental time course of myosin heavy chain (MHC) isoform transitions in single fibers of the rodent plantaris muscle. Hypothyroidism was used in conjunction with single-fiber analyses to better describe a possible linkage between the neonatal and fast type IIB MHC isoforms during development. In contrast to the general concept that developmental MHC isoform transitions give rise to muscle fibers that express only a single MHC isoform, the single-fiber analyses revealed a very high degree of MHC polymorphism throughout postnatal development. In the adult state, MHC polymorphism was so pervasive that the rodent plantaris muscles contained approximately 12-15 different pools of fibers (i.e., fiber types). The degree of polymorphism observed at the single-fiber level made it difficult to determine specific developmental schemes analogous to those observed previously for the rodent soleus muscle. However, hypothyroidism was useful in that it confirmed a possible link between the developmental regulation of the neonatal and fast type IIB MHC isoforms.

NASA Program Biomedical Research and Countermeasur↗

NASA NTRS1992

Influence of exercise training on the oxidative capacity of rat abdominal muscles

Our purpose was to determine if endurance exercise training would increase the oxidative capacity of the abdominal expiratory muscles of the rat. Accordingly, 9 male rats were subjected to an endurance training protocol (1 h/day, 6 days/week, 9 weeks) and 9 litter-mates served as controls. Citrate synthase (CS) activity was used as an index of oxidative capacity, and was determined in the following muscles: soleus, plantaris, costal diaphragm, crural diaphragm, and in all four abdominal muscles: rectus abdominis, transversus abdominis, external oblique, and internal oblique. Compared to their non-trained litter-mates, the trained rats had higher peak whole body oxygen consumption rates (+ 16%) and CS activities in plantaris (+34%) and soleus (+36%) muscles. Thus, the training program caused substantial systemic and locomotor muscle adaptations. The CS activity of costal diaphragm was 20% greater in the trained animals, but no difference was observed in crural diaphragm. The CS activity in the abdominal muscles was less than one-half of that in locomotor and diaphragm muscles, and there were no significant changes with training except in the rectus abdominis where a 26% increase was observed. The increase in rectus abdominis CS activity may reflect its role in postural support and/or locomotion, as none of the primary expiratory pumping muscles adapted to the training protocol. The relatively low levels of CS activity in the abdominal muscles suggests that they are not recruited frequently at rest, and the lack of an increase with training indicates that these muscles do not contribute significantly to the increased ventilatory activity accompanying exercise in the rat.

Non-NASA Center↗

NASA NTRS1992

Adaptability of the oxidative capacity of motoneurons

Previous studies have demonstrated that a chronic change in neuronal activation can produce a change in soma oxidative capacity, suggesting that: (i) these 2 variables are directly related in neurons and (ii) ion pumping is an important energy requiring activity of a neuron. Most of these studies, however, have focused on reduced activation levels of sensory systems. In the present study the effect of a chronic increase or decrease in motoneuronal activity on motoneuron oxidative capacity and soma size was studied. In addition, the effect of chronic axotomy was studied as an indicator of whether cytoplasmic volume may also be related to the oxidative capacity of motoneurons. A quantitative histochemical assay for succinate dehydrogenase activity was used as a measure of motoneuron oxidative capacity in experimental models in which chronic electromyography has been used to verify neuronal activity levels. Spinal transection reduced, and spinal isolation virtually eliminated lumbar motoneuron electrical activity. Functional overload of the plantaris by removal of its major synergists was used to chronically increase neural activity of the plantaris motor pool. No change in oxidative capacity or soma size resulted from either a chronic increase or decrease in neuronal activity level. These data indicate that the chronic modulation of ionic transport and neurotransmitter turnover associated with action potentials do not induce compensatory metabolic responses in the metabolic capacity of the soma of lumbar motoneurons. Soma oxidative capacity was reduced in the axotomized motoneurons, suggesting that a combination of axoplasmic transport, intracellular biosynthesis and perhaps neurotransmitter turnover represent the major energy demands on a motoneuron. While soma oxidative capacity may be closely related to neural activity in some neural systems, e.g. visual and auditory, lumbar motoneurons appear to be much less sensitive to modulations in chronic activity levels.

NASA Discipline Musculoskeletal↗

DOE OSTI2025

Markers of mitochondrial function and oxidative metabolism in skeletal muscle do not display intrinsic circadian regulation in female mice

Mitochondria are key regulators of metabolism and ATP supply in skeletal muscle, while circadian rhythms influence many physiological processes. However, whether mitochondrial function is intrinsically regulated in a circadian manner in mouse skeletal muscle is inadequately understood. Accordingly, we measured postabsorptive transcript abundance of markers of mitochondrial autophagy, dynamics, and metabolism [extensor digitorum longus (EDL), soleus, gastrocnemius], protein abundance of electron transport chain complexes (EDL and soleus), enzymatic activity of succinate dehydrogenase (tibialis anterior and plantaris), and maximal mitochondrial respiration (tibialis anterior) in different skeletal muscles from female C57BL/6NJ mice at four zeitgeber times: 1, 7, 13, and 19. Our findings demonstrate that markers of mitochondrial function and oxidative metabolism do not display intrinsic time-of-day regulation at the gene, protein, enzymatic, or functional level. The core-clock genes Bmal1 and Dbp exhibited intrinsic circadian rhythmicity in skeletal muscle (i.e., EDL, soleus, gastrocnemius) and circadian amplitude varied by muscle type. These findings demonstrate that female mouse skeletal muscle does not display circadian regulation of markers of mitochondrial function or oxidative metabolism over 24 h.

Circadian Biology↗

NASA NTRS1981

Experiment K-308: Automatic analysis of muscle fibers from rats subjected to spaceflight

The morphology of histochemically prepared muscle sections from the gastrocnemius and plantaris muscles of flight and vivarium control rats was studied quantitatively. Both fast-twitch and slow-twitch fibers were significantly smaller in flight groups than in control groups. Fibers in group 4F were somewhat larger than in 1F, presumably due to growth after recovery. Fibers in 4V were slightly larger than in 1V, presumably due to age. The slow fibers showed more spaceflight induced size loss than fast fibers, suggesting they suffered more from hypogravity. The proportion of slow fibers was also lower in the flight groups, suggesting spaceflight induced fiber type conversion from slow to fast.

Castleman, K. R.↗

NASA NTRS1982

Suspension restraint - Induced hypokinesia and antiorthostasis as a simulation of weightlessness

Muscle, renal, fluid and electrolyte responses were measured in suspended rats; the hind limbs are non-load bearing and the front limbs can be used for feeding and grooming. Hind limb hypokinesia reverses after removal from the suspension harness. This suspension system is adjustable for a head-down tilt to produce antiorthostatic responses which are also reversible. Responses to hypokinesia or antiorthostatic hypokinesia for up to 14 days were measured, e.g., muscle atrophy: soleus greater than gastrocnemius equals plantaris greater than extensor digitorum longus, kaliuresis, and increased excretion of urea, NH3, and 3 methylhistidine. Muscle protein loss, a response to a reduction in RNA, is also reversible. A head-down tilt for 7-14 days results in diuresis and natriuresis. These changes are reversed within 24 hours after removal from the restraint harness. Physiological effects of suspension restraint can be used to simulate and predict responses to microgravity exposure.

Musacchia, X. J.↗

NASA NTRS1984

Metabolic alterations caused by suspension hypokinesia in leg muscles of rats

Metabolic changes on hypokinetic rats were measured. Two groups of animals were studied: (1) weight bearing control which were tail casted but allowed to walk on all four limbs, and (2) hypokinetic with no load bearing of the hindlimbs. The control and hypokinetic rats gained weight at a steady and similar rate over 6 days. Hypokinesia for 6 days led to significantly lower relative weights of the soleus, gastrocnemius and plantaris muscles. Hypokinesia did not effect the relative mass of the anterior tibialis or extensor digitorum longus (EDL) muscles.

Tischler, M. E.↗