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At least 73 records · Page 4

Skeletal muscle atrophy in response to 14 days of weightlessness - Vastus medialis

The vastus medialis (VM) response from rats after 14 days of microgravity on Cosmos 2044 (F) have been studied by comparing it with VM from tail-suspended hindlimb-unloaded rats (T) and ground controls. The experimental approaches encompassed a histochemical evaluation of microscopic morphology, including fibers and capillaries; an assessment of biochemical composition including protein, DNA, and RNA concentrations; and an estimation of metabolic capacity. It is concluded that some significant changes were observed in the VM in rats exposed to weightlessness for 14 days. There is a loss in weight compared with the vivarium controls but not in comparison with synchronous and basal controls. Although there were minimal muscle weight differences between groups, muscle weight may be a less sensitive measure of change or atrophy than fiber area measurements. It is suggested that the nonload-bearing muscles, including the VM, show measurable responses to weightless flight.

Musacchia, X. J.↗

The nature of the autonomic dysfunction in multiple system atrophy

The concept that multiple system atrophy (MSA, Shy-Drager syndrome) is a disorder of the autonomic nervous system is several decades old. While there has been renewed interest in the movement disorder associated with MSA, two recent consensus statements confirm the centrality of the autonomic disorder to the diagnosis. Here, we reexamine the autonomic pathophysiology in MSA. Whereas MSA is often thought of as "autonomic failure", new evidence indicates substantial persistence of functioning sympathetic and parasympathetic nerves even in clinically advanced disease. These findings help explain some of the previously poorly understood features of MSA. Recognition that MSA entails persistent, constitutive autonomic tone requires a significant revision of our concepts of its diagnosis and therapy. We will review recent evidence bearing on autonomic tone in MSA and discuss their therapeutic implications, particularly in terms of the possible development of a bionic baroreflex for better control of blood pressure.

NASA Discipline Regulatory Physiology↗

Skeletal muscle calcineurin: influence of phenotype adaptation and atrophy

Calcineurin (CaN) has been implicated as a signaling molecule that can transduce physiological stimuli (e.g., contractile activity) into molecular signals that initiate slow-fiber phenotypic gene expression and muscle growth. To determine the influence of muscle phenotype and atrophy on CaN levels in muscle, the levels of soluble CaN in rat muscles of varying phenotype, as assessed by myosin heavy chain (MHC)-isoform proportions, were determined by Western blotting. CaN levels were significantly greater in the plantaris muscle containing predominantly fast (IIx and IIb) MHC isoforms, compared with the soleus (predominantly type I MHC) or vastus intermedius (VI, contains all 4 adult MHC isoforms). Three months after a complete spinal cord transection (ST), the CaN levels in the VI muscle were significantly reduced, despite a significant increase in fast MHC isoforms. Surprisingly, the levels of CaN in the VI were highly correlated with muscle mass but not MHC isoform proportions in ST and control rats. These data demonstrate that CaN levels in skeletal muscle are highly correlated to muscle mass and that the normal relationship with phenotype is lost after ST.

NASA Discipline Musculoskeletal↗

Depletion of catecholaminergic neurons of the rostral ventrolateral medulla in multiple systems atrophy with autonomic failure

The ventrolateral portion of the intermediate reticular formation of the medulla (ventrolateral medulla, VLM), including the C1/A1 groups of catecholaminergic neurons, is thought to be involved in control of sympathetic cardiovascular outflow, cardiorespiratory interactions, and reflex control of vasopressin release. As all these functions are affected in patients with multiple systems atrophy (MSA) with autonomic failure, we sought to test the hypothesis that catecholaminergic (tyrosine hydroxylase [TH]-positive) neurons of the VLM are depleted in these patients. Medullas were obtained at autopsy from 4 patients with MSA with prominent autonomic failure and 5 patients with no neurological disease. Patients with MSA had laboratory evidence of severe adrenergic sudomotor and cardiovagal failure. Tissue was immersion fixed in 2% paraformaldehyde at 4 degrees C for 24 hours and cut into 1-cm blocks in the coronal plane from throughout the medulla. Serial 50-microm sections were collected and one section every 300 microm was stained for TH. There was a pronounced depletion of TH neurons in the rostral VLM in all cases of MSA. There was also significant reduction of TH neurons in the caudal VLM in 3 MSA patients compared with 3 control subjects. In 2 MSA cases and in 2 control subjects, the thoracic spinal cord was available for study. There was also depletion of TH fibers and sympathetic preganglionic neurons (SPNs) in the 2 MSA cases examined. Thus, depletion of catecholaminergic neurons in the VLM may provide a substrate for some of the autonomic and endocrine manifestations of MSA.

Non-NASA Center↗

Mechanical Vibrations Reduce the Intervertebral Disc Swelling and Muscle Atrophy from Bed Rest

Loss of functional weight bearing, such as experienced during space flight or bed rest (BR), distorts intervertebral disc (IVD) and muscle morphology. IVDs are avascular structures consisting of cells that may derive their nutrition and waste removal from the load induced fluid flow into and out of the disc. A diurnal cycle is produced by forces related to weight bearing and muscular activity, and comprised of a supine and erect posture over a 24 hr period. A diurnal cycle will include a disc volume change of approx. 10-13%. However, in space there are little or no diurnal changes because of the microgravity, which removes the gravitational load and compressive forces to the back muscles. The BR model and the etiology of the disc swelling and muscle atrophy could provide insight into those subjects confined to bed for chronic disease/injury and aging. We hypothesize that extremely low-magnitude, high frequency mechanical vibrations will abate the disc degeneration and muscle loss associated with long-term BR.

Holguin, Nilsson↗

A Ground-Based Comparison of the Muscle Atrophy Research and Exercise System (MARES) and a Standard Isokinetic Dynamometer

PURPOSE: 1) To compare the test-to-test reliability of Muscle Atrophy Research and Exercise System (MARES) with a standard laboratory isokinetic dynamometer (ISOK DYN) and; 2) to determine if measures of peak torque and total work differ between devices. METHODS: Ten subjects (6M, 4F) completed two trials on both MARES and an ISOK DYN in a counterbalanced order. Peak torque values at 60 deg & 180 deg / s were obtained from five maximal repetitions of knee extension (KE) and knee flexion (KF). Total work at 180 deg / s was determined from the area under the torque vs. displacement curve during twenty maximal repetitions of KE and KF. Reliability of measures within devices was interpreted from the intraclass correlation coefficient (ICC) and compared between devices using the ratio of the within-device standard deviations. Indicators of agreement for the two devices were evaluated from: 1) a calculation of concordance (rho) and; 2) the correlation between the mean of measures versus the delta difference between measures (m u vs delta). RESULTS: For all outcome measures ICCs were high for both the ISOK DYN (0.95-0.99) and MARES (0.90-0.99). However, ratios of the within-device standard deviation were 1.3 to 4.3 times higher on MARES. On average, a wide range (3.3 to 1054 Nm) of differences existed between the values obtained. Only KE peak torque measured at 60 deg & 180 deg / s showed similarities between devices (rho = 0.91 & 0.87; Pearson's r for m u vs delta = -0.22 & -0.37, respectively). CONCLUSION: Although MARES was designed for use in microgravity it was quite reliable during ground-based testing. However, MARES was consistently more variable than an ISOK DYN. Future longitudinal studies evaluating a change in isokinetic peak torque or total work should be limited within one device.

Hackney, K. J.↗

Atypical form of Alzheimer's disease with prominent posterior cortical atrophy: a review of lesion distribution and circuit disconnection in cortical visual pathways

In recent years, the existence of visual variants of Alzheimer's disease characterized by atypical clinical presentation at onset has been increasingly recognized. In many of these cases post-mortem neuropathological assessment revealed that correlations could be established between clinical symptoms and the distribution of neurodegenerative lesions. We have analyzed a series of Alzheimer's disease patients presenting with prominent visual symptomatology as a cardinal sign of the disease. In these cases, a shift in the distribution of pathological lesions was observed such that the primary visual areas and certain visual association areas within the occipito-parieto-temporal junction and posterior cingulate cortex had very high densities of lesions, whereas the prefrontal cortex had fewer lesions than usually observed in Alzheimer's disease. Previous quantitative analyses have demonstrated that in Alzheimer's disease, primary sensory and motor cortical areas are less damaged than the multimodal association areas of the frontal and temporal lobes, as indicated by the laminar and regional distribution patterns of neurofibrillary tangles and senile plaques. The distribution of pathological lesions in the cerebral cortex of Alzheimer's disease cases with visual symptomatology revealed that specific visual association pathways were disrupted, whereas these particular connections are likely to be affected to a less severe degree in the more common form of Alzheimer's disease. These data suggest that in some cases with visual variants of Alzheimer's disease, the neurological symptomatology may be related to the loss of certain components of the cortical visual pathways, as reflected by the particular distribution of the neuropathological markers of the disease.

Review↗

The influence of exercise on bone atrophy

The relationship between the skeletal system, the muscular system, and exercise in bed rest studies are described. The regime of exercises performed, the mineral balance data derived, and the bone densitometric data obtained are discussed. A brief review of some of the histological results are also given.

Source record↗

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.↗

Alterations in skeletal muscle with disuse atrophy

Progress is reported in the following areas: (1) microgel electrophoresis identification of single fibers; (2) skinned fiber preparation; and (3) microbiochemical techniques for assaying important enzymes and substrates in single fibers.

Fitts, R. H.↗

Constant Fiber Number During Skeletal Muscle Atrophy and Modified Arachidonate Metabolism During Hypertrophy

A previously documented shift from Type I to IIA predominance of the soleus muscle during rat suspension was further investigated to determine if this shift was by selective reduction of a single fiber type, simultaneous reduction and formation of fibers with different fiber types, or a transformation of fiber type by individual fibers. By partial acid digestion and dissection, average total soleus fiber number was found to be 3022 + or - 80 (SE) and 3008 + or - 64 before and after four-week suspension (n=12). Another area of current research was based on previous studies which indicate that prostaglandins are biosynthesized by skeletal muscle and evoke protein synthesis and degradation.

Templeton, G.↗

Effects of Muscle Atrophy on Motor Control: Cage-size Effects

Two populations of male Sprague-Dawley rats were raised either in conventional minimum-specification cages or in a larger cage. When the animals were mature (125 to 150 d), the physiological status of the soleus (SOL) and extensor digitorum longus (EDL) muscles of the small- and large-cage animals were compared. Analysis of whole-muscle properties including the performance of the test muscle during a standardized fatigue test in which the nerve to the test muscle was subjected to supramaximal intermittent stimulation shows: (1) the amplitude, area, mean amplitude, and peak-to-peak rate of the compound muscle action potential decreased per the course of the fatigue test; (2) cage size did not affect the profile of changes for any of the action-potential measurements; (3) changes exhibited in the compound muscle action potential by SOL and EDL were substantially different; and (4) except for SOL of the large-cage rats, there was a high correlation between all four measures of the compound muscle action potential and the peak tetanic force during the fatigue test; i.e., either the electrical activity largely etermines the force profile during the fatigue test or else contractile-related activity substantially affects the compound muscle action potential.

Stuart, D. G.↗

Role of carbonic anhydrase in bone - Partial inhibition of disuse atrophy of bone by parenteral acetazolamide

The effectiveness of orally and subcutaneously administered acetazolamide sodium in preventing denervation-induced bone loss in rats is examined. Male Sprague-Dawley rats were treated with acetazolamide either orally by incorporation of 0.2, 0.5, or 1.5 percent concentrations in their diet for 15 days, or subcutaneously by either injection of 0.5 ml/rat of a solution containing either 20 or 100 mg/ml of the drug twice daily for 15 days or by continuous infusion of 5, 50, 500, or 1000 mg/ml of acetazolamide sodium for 8 days using an osmotic minipump. The effects of acetazolamide on body weight, food consumption, and plasma calcium content are evaluated. It is observed that parenteral administration is equally effective as oral administration in partially preventing denervation-induced bone mass changes. The data reveal that approximately 50 percent protection occurs with daily doses of 1094, 129, and 8 mg/kg body weight for the oral, subcutaneous injection, and subcutaneous infusion methods, respectively.

Kenny, A. D.↗

Disuse atrophy, plasma corticosterone, and muscle glucocorticoid receptor levels

The effect of whole-body suspension on the time course and the extent of plasma corticosterone changes and the tissue sensitivity to glucocorticoids were investigated in rats subjected to seven days of whole-body suspension. Plasma corticosterone increased significantly on the first and the third days of suspension, but returned to control levels by day seven. Muscle glucocorticoid receptors exhibited a characteristic hormonal specificity (evaluated in competitive-displacement experiments). In controls, receptor site concentration in the slow-twitch soleus was comparable to that in the fast-twitch gastrocnemius and plantaris, but was significantly less than in the extensor; seven days of suspension resulted in significant differential effects on muscle receptor levels. The largest increase in receptor concentration was observed in the soleus in which it remained elevated after the receptor levels in other muscles returned to normal.

Steffen, J. M.↗

Clenbuterol, a beta(2)-agonist, retards atrophy in denervated muscles

The effects of a beta(2) agonist, clenbuterol, on the protein content as well as on the contractile strength and the muscle fiber cross-sectional area of various denervated muscles from rats were investigated. It was found that denervated soleus, anterior tibialis, and gastrocnemius muscles, but not the extensor digitorum longus, of rats treated for 2-3 weeks with clenbuterol contained 95-110 percent more protein than denervated controls. The twofold difference in the protein content of denervated solei was paralleled by similar changes in contractile strength and muscle fiber cross-sectional area.

Zeman, Richard J.↗

Atrophy of the soleus muscle by hindlimb unweighting

This paper reviews data derived from the animal hindlimb unweighting model. The review presents the following information about the unweighted soleus muscle: electromyogram activity, the amount and type of protein lost, capillarization, oxidative capacity, glycolytic enzyme activities, fiber cross section, contractile properties, glucose uptake, sensitivity to insulin, the rates of protein synthesis and degradation, the glucocorticoid receptor numbers, the responses of specific mRNAs, and changes in metabolic concentrations. Data of all these studies show that the stress response of the animal to hindlimb suspension is transient and minimal in magnitude (though somewhat variable) and that, after one week of unweighting, the animal exhibits no chronic signs of stress.

Thomason, Donald B.↗