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Dystrophic Muscle (dystrophic + muscle)

Distribution by Scientific Domains
Medical Sciences83%

Selected Abstracts

Nerve-terminal and Schwann-cell response after nerve injury in the absence of nitric oxide

MUSCLE AND NERVE, Issue 2 2006
Maria Julia Marques PhD
Abstract Dystrophic muscles show alterations in the dystrophin,glycoprotein complex and a lack of neuronal nitric oxide (NO) synthase. In mdx mice, presynaptic expression of neuronal NO synthase is decreased, suggesting that presynaptic signaling may be altered in dystrophic muscle. In this study, we examined the nerve-terminal and Schwann-cell responses after a crush lesion in control and NO-deficient mice. Seven days after nerve crush, 24% of control neuromuscular junctions (n = 200) showed ultraterminal sprouts, whereas in NO-deficient mice this frequency was 28.5% (n = 217; P > 0.05 compared to controls; chi-square test). Schwann-cell response did not change in the absence of NO, after a nerve lesion of 7-day duration. Fourteen days after the lesion, nerve terminals sprouted and Schwann cells showed an extensive network of processes away from the synaptic site in controls. In the absence of NO, there was a dramatic decrease in nerve-terminal sprouting and Schwann-cell processes failed to extend away from the endplate. These results show that NO is involved in the nerve-terminal and Schwann-cell response to nerve injury. They also suggest that presynaptic molecular signaling may be impaired in dystrophic muscles, and this could influence the innervation and survival of newly formed myofibers generated by cell-mediated therapies. Muscle Nerve, 2006 [source]

SKELETAL MUSCLE FUNCTION: ROLE OF IONIC CHANGES IN FATIGUE, DAMAGE AND DISEASE

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2004
DG Allen
SUMMARY 1.,Repeated activity of skeletal muscle causes a variety of changes in its properties: muscles become weaker with intense use (fatigue), may feel sore and weak after repeated contractions involving stretch and can degenerate in some disease conditions. The present review considers the role of early ionic changes in the development of each of these conditions. 2.,Single fibre preparations of mouse muscle were used to measure ionic changes following activity induced changes in function. Single fibres were dissected with intact tendons and stimulated to produce force. Fluorescent indicators were microinjected into the fibres to allow simultaneous ionic measurements with determination of mechanical performance. 3.,One theory to explain muscle fatigue is that fatigue is caused by the accumulation of lactic acid, producing an intracellular acidosis that inhibits the myofibrillar proteins. In contrast, we found that during repeated tetani there was little or no pH change, but that failure of calcium release was a major contributor to fatigue. Currently, it is proposed that precipitation of calcium and phosphate in the sarcoplasmic reticulum contributes to the failure of calcium release. 4.,Muscles can be used to shorten and produce force or they can be used to de-accelerate loads (stretched or eccentric contractions). One day after intense exercise involving stretched contractions, muscles are weak, sore and tender, and this damage can take a week to recover. In this condition, sarcomeres are disorganized and there are increases in resting intracellular Ca2+ and Na+. Recently, we demonstrated that the elevation of Na+ occurs through a stretch-activated channel that can be blocked by either gadolinium or streptomycin. Preventing the increase in [Na+]i with gadolinium also prevented part of the muscle weakness after stretched contractions. 5.,Duchenne muscular dystrophy is a lethal degenerative disease of muscles in which the protein dystrophin is absent. Dystrophic muscles are more susceptible to stretch-induced muscle damage and the stretch-activated channel seems to be one pathway for the increases in intracellular Ca2+ and Na+ that are a feature of this disease. We have shown recently that blockers of the stretch-activated channel can minimize some of the short-term damage in muscles from the mdx mouse, which also lacks dystrophin. Currently, we are testing whether blockers of the stretch-activated channels given systemically to mdx mice can protect against some features of the disease. [source]

Nerve-terminal and Schwann-cell response after nerve injury in the absence of nitric oxide

MUSCLE AND NERVE, Issue 2 2006
Maria Julia Marques PhD
Abstract Dystrophic muscles show alterations in the dystrophin,glycoprotein complex and a lack of neuronal nitric oxide (NO) synthase. In mdx mice, presynaptic expression of neuronal NO synthase is decreased, suggesting that presynaptic signaling may be altered in dystrophic muscle. In this study, we examined the nerve-terminal and Schwann-cell responses after a crush lesion in control and NO-deficient mice. Seven days after nerve crush, 24% of control neuromuscular junctions (n = 200) showed ultraterminal sprouts, whereas in NO-deficient mice this frequency was 28.5% (n = 217; P > 0.05 compared to controls; chi-square test). Schwann-cell response did not change in the absence of NO, after a nerve lesion of 7-day duration. Fourteen days after the lesion, nerve terminals sprouted and Schwann cells showed an extensive network of processes away from the synaptic site in controls. In the absence of NO, there was a dramatic decrease in nerve-terminal sprouting and Schwann-cell processes failed to extend away from the endplate. These results show that NO is involved in the nerve-terminal and Schwann-cell response to nerve injury. They also suggest that presynaptic molecular signaling may be impaired in dystrophic muscles, and this could influence the innervation and survival of newly formed myofibers generated by cell-mediated therapies. Muscle Nerve, 2006 [source]

The prion protein in human neuromuscular diseases

THE JOURNAL OF PATHOLOGY, Issue 3 2004
Gábor G Kovács
Abstract The basis of human prion diseases affecting the nervous system is accumulation of a disease-associated conformer (PrPSc) of the normal cellular prion protein (PrPC). Earlier studies demonstrated increased expression of PrPC in inclusion body myositis (IBM), dermato-, and polymyositis, as well as neurogenic muscle atrophy. To define the spectrum and reliability of PrPC immunoreactivity, its expression was examined systematically in a series of pathologically characterized muscular disorders by means of immunohistochemistry, confocal laser microscopy, and immunogold electron microscopy. Anti-PrPC immunolabelling of rimmed vacuoles was observed in IBM, inclusions of myofibrillary myopathy, targets, regenerating, and atrophic fibres, mononuclear cells, in addition to ragged red fibres in mitochondrial myopathies, and focal sarcolemmal immunostaining in non-diseased controls. Quantitative analysis demonstrated that, in neurogenic muscle lesions, anti-PrPC staining detects a significantly broader spectrum of fibres than anti-vimentin or anti-NCAM. In dystrophic muscle, PrPC expression was mainly restricted to regenerating fibres. In IBM, PrPC expression was not confined to rimmed vacuoles or vacuolated fibres and only a small percentage (7.1%) of rimmed vacuoles were PrPC positive. Ultrastructurally, PrPC was observed in the cytoplasm of lymphocytes, in the myofibrillar network of targets, and in rimmed vacuoles. Knowledge of disease circumstances with altered expression of PrPC is important in the setting of a potentially increased chance for extraneural PrPC,PrPSc conversion. In addition, our observations suggest that PrPC may have a general stress,response effect in various neuromuscular disorders. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Mechanisms of stretch-induced muscle damage in normal and dystrophic muscle: role of ionic changes

THE JOURNAL OF PHYSIOLOGY, Issue 3 2005
D. G. Allen
Muscle damage, characterized by prolonged weakness and delayed onset of stiffness and soreness, is common following contractions in which the muscles are stretched. Stretch-induced damage of this sort is more pronounced in the muscular dystrophies and the profound muscle damage observed in these conditions may involve similar pathways. It has been known for many years that damaged muscles accumulate calcium and that elevating calcium in normal muscles simulates many aspects of muscle damage. The changes in intracellular calcium, sodium and pH following stretched contractions are reviewed and the various pathways which have been proposed to allow ion entry are discussed. One possibility is that TRPC1 (transient receptor potential, canonical), a protein which seems to form both a stretch-activated channel and a store-operated channel, is the main source of Ca2+ entry. The mechanisms by which the changes in intracellular ions contribute to reduced force production, to increased protein breakdown and to increased membrane permeability are considered. A hypothetical scheme for muscle damage which incorporates these ideas is presented. [source]

Nerve-terminal and Schwann-cell response after nerve injury in the absence of nitric oxide

MUSCLE AND NERVE, Issue 2 2006
Maria Julia Marques PhD
Abstract Dystrophic muscles show alterations in the dystrophin,glycoprotein complex and a lack of neuronal nitric oxide (NO) synthase. In mdx mice, presynaptic expression of neuronal NO synthase is decreased, suggesting that presynaptic signaling may be altered in dystrophic muscle. In this study, we examined the nerve-terminal and Schwann-cell responses after a crush lesion in control and NO-deficient mice. Seven days after nerve crush, 24% of control neuromuscular junctions (n = 200) showed ultraterminal sprouts, whereas in NO-deficient mice this frequency was 28.5% (n = 217; P > 0.05 compared to controls; chi-square test). Schwann-cell response did not change in the absence of NO, after a nerve lesion of 7-day duration. Fourteen days after the lesion, nerve terminals sprouted and Schwann cells showed an extensive network of processes away from the synaptic site in controls. In the absence of NO, there was a dramatic decrease in nerve-terminal sprouting and Schwann-cell processes failed to extend away from the endplate. These results show that NO is involved in the nerve-terminal and Schwann-cell response to nerve injury. They also suggest that presynaptic molecular signaling may be impaired in dystrophic muscles, and this could influence the innervation and survival of newly formed myofibers generated by cell-mediated therapies. Muscle Nerve, 2006 [source]