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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 379 records · Page 21
All sourcesNASA NTRSDOE OSTI
NASA NTRS1997

Growth hormone, IGF-I, and exercise effects on non-weight-bearing fast muscles of hypophysectomized rats

The effects of growth hormone (GH) or insulin-like growth factor I (IGF-I) with or without exercise (ladder climbing) in countering the effects of unweighting on fast muscles of hypophysectomized rats during 10 days of hindlimb suspension were determined. Compared with untreated suspended rats, muscle weights were 16-29% larger in GH-treated and 5-15% larger in IGF-I-treated suspended rats. Exercise alone had no effect on muscle weights. Compared with ambulatory control, the medial gastrocnemius weight in suspended, exercised rats was larger after GH treatment and maintained with IGF-I treatment. The combination of GH or IGF-I plus exercise in suspended rats resulted in an increase in size of each predominant fiber type, i.e., types I, I + IIa and IIa + IIx, in the medial gastrocnemius compared with untreated suspended rats. Normal ambulation or exercise during suspension increased the proportion of fibers expressing embryonic myosin heavy chain in hypophysectomized rats. The phenotype of the medial gastrocnemius was minimally affected by GH, IGF-I, and/or exercise. These results show that there is an IGF-I, as well as a GH, and exercise interactive effect in maintaining medial gastrocnemius fiber size in suspended hypophysectomized rats.

NASA Center ARC↗
DOE OSTI2022

Elamipretide effects on the skeletal muscle phosphoproteome in aged female mice

The age-related decline in skeletal muscle mass and function is known as sarcopenia. Sarcopenia progresses based on complex processes involving protein dynamics, cell signaling, oxidative stress, and repair. We have previously found that 8-week treatment with elamipretide improves skeletal muscle function, reverses redox stress, and restores protein S-glutathionylation changes in aged female mice. This study tested whether 8-week treatment with elamipretide also affects global phosphorylation in skeletal muscle consistent with functional improvements and S-glutathionylation. Using female 6–7-month-old mice and 28–29-month-old mice, we found that phosphorylation changes did not relate to S-glutathionylation modifications, but that treatment with elamipretide did partially reverse age-related changes in protein phosphorylation in mouse skeletal muscle.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

The impact of bilateral injuries on the pathophysiology and functional outcomes of volumetric muscle loss

Volumetric muscle loss (VML)—defined as the irrecoverable loss of skeletal muscle tissue with associated persistent functional deficits—is among the most common and highly debilitating combat-related extremity injuries. This is particularly true in cases of severe polytrauma wherein multiple extremities may be involved as a result of high energy wounding mechanisms. As such, significant investment and effort has been made toward developing a clinically viable intervention capable of restoring the form and function of the affected musculature. While these investigations conducted to date have varied with respect to the species, breed, and sex of the chosen pre-clinical in-vivo model system, the majority of these studies have been performed in unilateral injury models, an aspect which may not fully exemplify the clinical representation of the multiply injured patient. Furthermore, while various components of the basal pathophysiology of VML (e.g., fibrosis and inflammation) have been investigated, relatively little effort has focused on how the pathophysiology and efficacy of pro-regenerative technologies is altered when there are multiple VML injuries. Thus, the purpose of this study was two-fold: (1) to investigate if/how the pathophysiology of unilateral VML injuries differs from bilateral VML injuries and (2) to interrogate the effect of bilateral VML injuries on the efficacy of a well-characterized regenerative therapy, minced muscle autograft (MMG). In contrast to our hypothesis, we show that bilateral VML injuries exhibit a similar systemic inflammatory response and improved muscle functional recovery, compared to unilateral injured animals. Furthermore, MMG treatment was found to only be effective at promoting an increase in functional outcomes in unilateral VML injuries. The findings presented herein add to the growing knowledge base of the pathophysiology of VML, and, importantly, reiterate the importance of comprehensively characterizing preclinical models which are utilized for early-stage screening of putative therapies as they can directly influence the translational research pipeline.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

Ampk alpha2 T172 activation dictates exercise performance and energy transduction in skeletal muscle

Adenosine 5′-monophosphate–activated protein kinase (AMPK) is an energetic sensor for metabolic regulation and integration. Here, we used CRISPR-Cas9 to generate nonactivatable Ampkα knock-in (KI) mice with mutation of threonine-172 phosphorylation site to alanine (T172A), circumventing the limitations of previous genetic interventions that disrupt the protein stoichiometry. KI mice of Ampkα2, but not Ampkα1, demonstrated phenotypic changes with increased fat-to-lean mass, impaired endurance exercise capacity, and diminished mitochondrial maximal respiration and conductance in skeletal muscle. Integrated temporal multiomics analysis (proteomics/phosphoproteomics/metabolomics) in skeletal muscle at rest and during exercise establishes a pleiotropic yet imperative role of Ampkα2 T172 activation for glycolytic and oxidative metabolism, mitochondrial respiration, and contractile function. There is a substantial overlap of skeletal muscle proteomic changes in Ampkα2 T172A KI mice with that of patients with type 2 diabetes. Our findings suggest that Ampkα2 T172 activation is critical for exercise performance and energy transduction in skeletal muscle and may serve as a therapeutic target for type 2 diabetes.

Bioenergetics↗
DOE OSTI2023

Neck Muscle Coactivation Response to Varied Levels of Mental Workload During Simulated Flight Tasks

Objective To evaluate neck muscle coactivation across different levels of mental workload during simulated flight tasks. Background Neck pain (NP) is highly prevalent among military aviators. Given the complex nature within the flight environment, mental workload may be a risk factor for NP. This may induce higher levels of neck muscle coactivity, which over time may accelerate fatigue, increase neck discomfort, and affect flight task performance. Method Three counterbalanced mental workload conditions represented by simulated flight tasks modulated by interstimulus frequency and complexity were investigated using the Modifiable Multitasking Environment (ModME). The primary measure was a neck coactivation index to describe the neuromuscular effort of the neck muscles as a system. Additional measures included perceived workload (NASA TLX), subjective discomfort, and task performance. Participants ( n = 60; 30M, 30F) performed three test conditions over 1 hr each while seated in a simulated seating environment. Results Neck coactivation indices (CoA) and subjective neck discomfort corresponded with increasing level of mental workload. Average CoAs for low, medium, and high workloads were: .0278(SD = .0232), .0286(SD = .0231), and .0295(SD = .0228), respectively. NASA TLX mental, temporal, effort, and overall scores also increased with the level of mental workload assigned. For ModME task performance, the overall performance score, monitoring accuracy, and resource management accuracy decreased while reaction times increased with the increasing level of mental workload. Communication accuracy was lowest with the low mental workload but had higher reaction times relative to increasing workload. Conclusion Mental workload affects neck muscle coactivation during combinations of simulated flight tasks within a simulated helicopter seating environment. Application The results of this study provide insights into the physical response to mental workload. With increasing multisensory modalities within the work environment, these insights may assist the consideration of physical effects from cognitive factors.

Behavioral Sciences↗
DOE OSTI2021

Dietary vitamin E reaches the mitochondria in the flight muscle of zebra finches but only if they exercise

Whether dietary antioxidants are effective for alleviating oxidative costs associated with energy-demanding life events first requires they are successfully absorbed in the digestive tract and transported to sites associated with reactive species production (e.g. the mitochondria). Flying birds are under high energy and oxidative demands, and although birds commonly ingest dietary antioxidants in the wild, the bioavailability of these consumed antioxidants is poorly understood. We show for the first time that an ingested lipophilic antioxidant, α-tocopherol, reached the mitochondria in the flight muscles of a songbird but only if they regularly exercise (60 min of perch-to-perch flights two times in a day or 8.5 km day -1 ). Deuterated α-tocopherol was found in the blood of exercise-trained zebra finches within 6.5 hrs and in isolated mitochondria from pectoral muscle within 22.5 hrs, but never reached the mitochondria in caged sedentary control birds. This rapid pace (within a day) and extent of metabolic routing of a dietary antioxidant to muscle mitochondria means that daily consumption of such dietary sources can help to pay the inevitable oxidative costs of flight muscle metabolism, but only when combined with regular exercise.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1980

Hypodynamic and hypokinetic condition of skeletal muscles

Data are presented in regard to the effect of unilateral brachial amputation on the physiological characteristics of two functionally different muscles, the brachial muscle (flexor of the brachium) and the medial head of the brachial triceps muscle (extensor of the brachium), which in rats represents a separate muscle. Hypokinesia and hypodynamia were studied.

Katinas, G. S.↗
NASA NTRS1981

Protein synthesis rates in atrophied gastrocnemius muscles after limb immobilization

Noting that protein synthesis declines in the gastrocnemius 6 hr after immobilization, the study sought to detect an increase of protein synthesis when the limb was freed, and to examine the effects of exercise on the rate of increase. Rats were used as subjects, with their hind legs in plaster of Paris in plantar flexion to eliminate strain on the gastrocnemius. Periods of immobilization were varied and samples of blood from the muscle were taken to track protein synthesis rates for different groups in immobilization and exercise regimens (running and weightlifting). Synthesis rates declined 3.6% during time in the cast, then increased 6.3%/day after the casts were removed. Both running and weightlifting were found to increase the fractional rate of protein formation in the gastrocnemius muscle when compared with contralateral muscles that were not exercised and were used as controls, suggesting that the mechanism controlling protein synthesis in skeletal muscles is rapidly responsive to changes in muscular contractile activity.

Tucker, K. R.↗
NASA NTRS1981

Enhanced skeletal muscle insulin sensitivity in year-old rats adapted to hypergravity

Rats induced into a hypermetabolic state by exposure to chronic (7 mo) centrifugation at 4.15 g exhibited increased glucose uptake at lower plasma insulin levels than weight-matched control animals following oral glucose administration. In order to determine the insulin sensitivity of specific tissues, the effect of exogenous insulin on glucose uptake by isolated perfused livers and hindlim skeletal muscle from rats adapted to chronic centrifugation for one year was compared with perfused tissue from 2.5 mo-old noncentrifuged control animals of equal body weight. Metabolic glucose clearance by skeletal muscle from hypergravic rats did not prove significantly greater than control muscle when perfused in the absence of insulin (10.6 vs 8.1 microliters/min-g-muscle), but was twice as fast (23.0 vs 9.5) at perfusate insulin levels of 35 micro-U/ml. Conversely, glucose uptake by hypergravic livers was significantly decreased (P is less than 0.001) compared with control livers (10.3 vs 27.8) at perfusate insulin levels of 40 micro-U/ml. Results suggest that skeletal muscle rather than liver is primarily responsible for the enhanced sensitivity to insulin and the increased energy expenditure observed in rats subjected to hypergravity.

Mondon, C. E.↗
NASA NTRS1982

Morphometric analysis of rat muscle fibers following space flight and hypogravity

The effect of hypogravity on striate muscles, containing both fast twitch glycolytic and slow twitch oxidative fibers, was studied in rats aboard two Cosmos biosatellites. Results of a computer-assisted image analysis of extensor digitorum muscles from five rats, exposed to 18.5 days of hypogravity and processed for the alkaline ATPase reaction, showed a reduction of the mean fiber diameter (41.32 + or - 0.55 microns), compared to synchronous (46.32 + or - 0.55 microns) and vivarium (49 + or - 0.5 microns) controls. A further experiment studied the ratio of fast to slow twitch fibers in 25 rats exposed to 18.5 days of hypogravity and analyzed at four different periods of recovery following the space flight. Using the previous techniques, the gastrocnemius muscle showed a reduction of the total muscle fiber area in square microns and a reduction in the percentage of slow fibers of flight animals compared to the control animals.

Chui, L. A.↗
NASA NTRS1982

Atrophy of rat skeletal muscles in simulated weightlessness

A hypokinetic rat model was used for elucidation of the mechanism of skeletal muscle wasting which occurs in weightlessness. Rats were suspended from a back-harness with the head tilted downward and the hind limbs totally unloaded. A progressive decrease in the size of the soleus muscle from suspended rats was observed as a function of time. The rate of protein degradation of the homogenates from the soleus muscles of suspended and control animals was not significantly different. The rate of cell-free protein synthesis was severely repressed in the atrophied muscle. An initial rise in the levels of plasma glucose and corticosterone was observed on the second day of suspension, but they subsequently returned to normal values.

Feller, D. D.↗
NASA NTRS1983

Effect of hindlimb immobilization on the fatigability of skeletal muscle

The effect of 6 weeks of disuse atrophy produced by hindlimb immobilization was studied in situ (33.5 C) in the soleus and extensor digitorum longus muscles of rats. The results indicate that disuse causes preferential alterations in the isometric contractile properties of slow-twitch, as opposed to fast-twitch, skeletal muscles. During continuous contractile activity, atrophied muscles were found to have lower ATP levels and an apparent increase in their dependence on anaerobic metabolism, as reflected by the more extensive depletion of glycogen and enhanced lactate formation. Although the atrophied muscles were determined to have fewer cross bridges and thus generated lower tension, the pattern of decline in active cross-bridge formation and tetanic tension during contractile activity was found to proceed in a manner similar to controls.

Witzmann, F. A.↗
NASA NTRS1983

Androgens enhance in vivo 2-deoxyglucose uptake by rat striated muscle

It is shown that testosterone propionate (TP) causes a striking increase in the in vivo uptake of 2-deoxyglucose (2-DG) by the levator ani muscle of immature male rats, which was found to be uniformly distributed over the entire muscle. After a single subcutaneous injection of TP, no enhancement of 2-DG was observed before 3.5 hr, at which time uptake was increased 2-fold; maximum enhancement (4-fold) was attained at 12 hr. At 72 hr, 2-DG uptake remained elevated at twice the control value. It was determined that the effect of TP probably is mediated by specific androgen receptors. In addition, it was found that the effect of TP was blocked by the simultaneous administration of an androgen antagonist, cyproterone acetate. TP also was found to enhance the uptake of 2-DG in the bulbocavernosus (253 percent over control) and extensor digitorum longus muscles (150 percent over control), but not in the biceps brachii or soleus. It is suggested that the increased uptake of glucose may be an important early step in the anabolic response of muscle to androgens.

Max, S. R.↗
NASA NTRS1984

Physiological changes in fast and slow muscle with simulated weightlessness

A rat hindlimb suspension model of simulated weightlessness was used to examine the physiological characteristics of skeletal muscle. The physiological sequelae of hindlimb suspension were compared to those of spinal cord section, denervation by sciatic nerve crush, and control. Muscle examined were the predominantly slow (Type 1) soleus (SOL) and the predominantly fast (Type 2) extensor digitorum longus (EDL). Two procedures which alter motor unit activity, hindlimb suspension and spinal cord section, produce changes in characteristics of skeletal muscles that are dependent upon fiber type. The SOL develops characteristics more representative of a fast muscle, including smaller Type 1 fiber proportion and higher AChE activity. The EDL, which is already predominantly fast, loses most of its few Type 1 fibers, thus also becoming faster. These data are in agreement with the studies in which rats experienced actual weightlessness.

Dettbarn, W. D.↗
NASA NTRS1984

Research opportunities in muscle atrophy

Muscle atrophy in a weightless environment is studied. Topics of investigation include physiological factors of muscle atrophy in space flight, biochemistry, countermeasures, modelling of atrophied muscle tissue, and various methods of measurement of muscle strength and endurance. A review of the current literature and suggestions for future research are included.

Herbison, G. J.↗
NASA NTRS1983

Contractile properties of rat fast-twitch skeletal muscle during reinnervation - Effects of testosterone and castration

The peroneal nerve of subject rats were crushed 1 cm from the muscle in order to examine the isometric contractile properties of skeletal muscle in the recovery sequency during reinnervation of normal, castrated, and testosterone-treated rats. The particular muscle studied was the extensor digitorum longus, with functional reinnervation first observed 8-9 days after nerve crush. No evidence was found that either castration or testosterone injections altered the process of reinnervation after the nerve crush, with the conclusion being valid at the 0.05 p level. The most reliable index of reinnervation was found to be the twitch:tetanus ratio, a factor of use in future studies of the reinnervation of skeletal muscle.

Yeagle, S. P.↗
NASA NTRS1983

Glucocorticoid sensitivity, disuse, and the regulation of muscle mass

A new noninvasive immobilization procedure to be used on rats has been developed to study immobilization-induced muscle hypersensitivity to normal glucocorticoid concentration, subsequent muscle atrophy, and atrophy recovery. The immobilization procedure involves encasing the hind limb in a light-weight plasticlike cast (10 percent the usual plaster weight), completely resistant to animal gnawing. The effects of right-angle immobilization of the ankle on the slow fiber soleus, and the fast fiber extensor digitorum longus, resemble the effects of weightlessness. The increased concentration of glucocorticoid receptor sites in immobilized and denervated muscle is discussed, along with the chronic loss of muscle mass that occurs in practically all dystrophies. It is concluded that lack of mechanical work in a zero gravity environment is a major cause of glucocorticoid hypersensitivity in the body's musculature.

Almon, R. R.↗
NASA NTRS1983

Muscle and the physiology of locomotion

NASA's past, current, and planned research on muscle deterioration at zero gravity and development of countermeasures are reviewed; Soviet studies are discussed as well. A definition of muscle mass and strength regulation factors, and improved measurement methods of muscle atrophy are needed. Investigations of tissue growth factors and their receptors, endogenous and exogenous anabolic protein synthesis stimulation, and a potential neurotropic factor are among the projects in progress or planned. At present, vigorous physical exercise during spaceflight is recommended as the most effective countermeasure against skeletal muscle atrophy.

Rambaut, P. C.↗