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Results for “Muscle atrophy”

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At least 19 recordsLinked to original sources
PubMed1979

Elevated levels of a calcium-activated muscle protease in rapidly atrophying muscles from vitamin E-deficient rabbits.

A Ca2+-activated proteolytic enzyme that partially degrades myofibrils was isolated from hind limb muscles of normal rabbits and rabbits undergoing rapid muscle atrophy as a result of vitamin E deficiency. Extractable Ca2+-activated protease activity was 3.6 times higher in muscle tissue from vitamin E-deficient rabbits than from muscle tissue of control rabbits. Ultrastructural studies of muscle from vitamin E-deficient rabbits showed that the Z disk was the first myofibrillar structure to show degradative changes in atrophying muscle. Myofibrils prepared from muscles from vitamin E-deficient rabbits showed partial or complete loss of Z-disk density. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that the amount of troponin-T (37 000 daltons) and alpha-actinin (96 000 daltons) was reduced in myofibrils from atrophying muscle as compared to myofibrils prepared from control muscle. In vitro treatment of purified myofibrils with purified Ca2+-activated proteolytic enzyme produced alterations in myofibrillar ultrastructure that were identical to the initial alterations occurring in myofibrils from atrophying muscle (i.e. weakening and subsequent removal of Z disks). Additonally the electrophoretic banding pattern of Ca2+-activated proteolytic enzyme-treated myofibrils is very similar to that of myofibrils prepared from muscles atrophying as a result of nutritional vitamin E deficiency. The possible role of Ca2+-activated proteolytic enzyme in disassembly and degradation of the myofibril is discussed.

Animals↗
PubMed1977

Do hormonal (stress) and vascular (ischaemia) factors contribute to reflex muscle atrophy induced by chronic nociceptive stimulation in rats?

1. Reflex muscle atrophy was induced in rats by fracturing the metatarsal bones of one hind paw and injecting 0.02 ml turpentine oil into the planta under shortlasting ether anaesthesia. The atrophy thus evoked in the soleus and extensor digitorum longus (EDL) was compared with the contralateral muscles. 2. There was a twelvefold increase of plasma corticosteroid levels one hour after application of the above nociceptive stimulus and the levels were still somewhat enhanced at 3 days. Neither bilateral adrenalectomy nor administration of corticosteroid hormones or cold stress affected the development of reflex atrophy. 3. Restriction of the arterial blood supply (ligature of the common iliac artery) led to a slowly progressing atrophy with a maximum 10 days after the ligature. Reflex atrophy introduced at different times after ligature was not enhanced. 4. These results are interpreted as evidence that neither general stress (and the effect of catabolic hormones) nor local restriction of muscle blood flow (by reflex vasospasm, for example) are likely to play any appreciable role in the mechanism of reflex muscle atrophy.

Adrenal Cortex Hormones↗
PubMed2026

C9orf72-associated poly-GR in skeletal muscle leads to neuromuscular junction deficits and muscle atrophy.

Hexanucleotide repeat expansions in C9orf72 produce dipeptide repeat (DPR) proteins that are widely expressed, including in the nervous system and skeletal muscle. Among these DPRs, arginine-containing proteins, poly-GR and poly-PR, are toxic in the nervous system, but whether DPRs in skeletal muscle contribute to amyotrophic lateral sclerosis (ALS) pathogenesis is unclear. Here, we show that muscle-restricted expression of poly-GR drives motor deficits in mice, including muscle atrophy and neuromuscular junction (NMJ) deficits. Poly-GR in muscle interacted with the NMJ key organizer MuSK and promoted MuSK degradation, disrupting postsynaptic structure and impairing neuromuscular transmission. Importantly, a MuSK agonist antibody (X-17) stabilized NMJs and rescued neuromuscular transmission. Moreover, poly-GR in muscle activated the integrated stress response (ISR), elevating eIF2α phosphorylation and broadly suppressing protein translation. ISR inhibition with ISRIB restored translation and MuSK protein levels and ameliorated both muscle atrophy and NMJ deficits. These findings demonstrate that skeletal muscle actively contributes to C9orf72-ALS pathology. Targeting muscle with ISRIB offers a therapeutic strategy to preserve motor function in C9orf72-ALS.

Animals↗
PubMed2026

The miR-206-3p/Cpeb1 axis delays acetylcholine receptor degradation and preserves neuromuscular junction stability in denervation-induced muscle atrophy.

Peripheral nerve injury leads to progressive neuromuscular junction (NMJ) destabilization and acetylcholine receptor (AChR) degradation, which are critical drivers of denervation-induced muscle atrophy and impaired motor recovery. However, the post-transcriptional mechanisms regulating AChR stability during denervation remain poorly understood. Here, we investigated the role of miR-206-3p in NMJ maintenance and muscle preservation after denervation, with a focus on its interaction with the RNA-binding protein cytoplasmic polyadenylation element binding protein 1 (Cpeb1). Using C2C12 myoblasts and a sciatic nerve transection mouse model, we demonstrate that miR-206-3p promotes myogenic differentiation, enhances AChR clustering, and preserves postsynaptic AChR morphology. miR-206-3p directly targets the 3' untranslated region of Cpeb1, suppressing its expression, as confirmed by dual-luciferase reporter assays. In vivo, adeno-associated virus-mediated overexpression of miR-206-3p delayed denervation-induced AChR fragmentation, attenuated muscle atrophy, and significantly improved motor function recovery. Conversely, Cpeb1 overexpression accelerated AChR degradation and muscle wasting, whereas co-overexpression of miR-206-3p mitigated these detrimental effects, indicating that Cpeb1 is a key downstream effector of miR-206-3p. Collectively, our findings identify the miR-206-3p/Cpeb1 axis as a previously unrecognized regulator of NMJ stability and muscle integrity after denervation, providing mechanistic insight and a potential therapeutic target for preserving neuromuscular function during prolonged denervation.

Animals↗
PubMed2022

Lipid hydroperoxides and oxylipins are mediators of denervation induced muscle atrophy.

Loss of innervation is a key driver of age associated muscle atrophy and weakness (sarcopenia). Our laboratory has previously shown that denervation induced atrophy is associated with the generation of mitochondrial hydroperoxides and lipid mediators produced downstream of cPLA2 and 12/15 lipoxygenase (12/15-LOX). To define the pathological impact of lipid hydroperoxides generated in denervation-induced atrophy in vivo, we treated mice with liproxstatin-1, a lipid hydroperoxide scavenger. We treated adult male mice with 5 mg/kg liproxstain-1 or vehicle one day prior to sciatic nerve transection and daily for 7 days post-denervation before tissue analysis. Liproxstatin-1 treatment protected gastrocnemius mass and fiber cross sectional area (∼40% less atrophy post-denervation in treated versus untreated mice). Mitochondrial hydroperoxide generation was reduced 80% in vitro and by over 65% in vivo by liproxstatin-1 treatment in denervated permeabilized muscle fibers and decreased the content of 4-HNE by ∼25% post-denervation. Lipidomic analysis revealed detectable levels of 25 oxylipins in denervated gastrocnemius muscle and significantly increased levels for eight oxylipins that are generated by metabolism of fatty acids through 12/15-LOX. Liproxstatin-1 treatment reduced the level of three of the eight denervation-induced oxylipins, specifically 15-HEPE, 13-HOTrE and 17-HDOHE. Denervation elevated protein degradation rates in muscle and treatment with liproxstatin-1 reduced rates of protein breakdown in denervated muscle. In contrast, protein synthesis rates were unchanged by denervation. Targeted proteomics revealed a number of proteins with altered expression after denervation but no effect of liproxstain-1. Transcriptomic analysis revealed 203 differentially expressed genes in denervated muscle from vehicle or liproxstatin-1 treated mice, including ER stress, nitric oxide signaling, Gαi signaling, glucocorticoid receptor signaling, and other pathways. Overall, these data suggest lipid hydroperoxides and oxylipins are key drivers of increased protein breakdown and muscle loss associated with denervation induced atrophy and a potential target for sarcopenia intervention.

Male↗
PubMed1979

Central vestibular involvement in peroneal muscle atrophy: a preliminary report.

A family is presented in which 6 out of 8 members were found to have peroneal muscle atrophy. Neurophysiological and histopathological evidence for the hypertrophic form of this disease was obtained in 3 patients. Three patients with peroneal muscle atrophy and 1 unaffected family member had abnormal differential caloric tests. This is the first report of an apparently hereditary dysfunction of the central vestibular system associated with a hereditary neuropathy.

Caloric Tests↗
PubMed1979

Localization of non-specific esterase and acid phosphatase in human fibroblast from skeletal muscle atrophy.

The intracellular localization of non-specific esterase and acid phosphatase was investigated in human fibroblast cells from skeletal muscle atrophy. Non-specific esterase and acid phosphatase positive sites were visualized ultrastructurally in the fibroblast. Electron microscopy for the cytochemistry of these enzyme was performed in human atrophic skeletal muscle by using thiol acetate esterase method and GOMORI'S method. Lipofuscin pigment granules in fibroblast cells contain dense pigment, granular matrix and lipid droplet. Reaction products of non-specific esterase are seen in the pigment and granular matrix, and they may therefore be called residual bodies. Reaction products of acid phosphatase and non-specific esterase were found to be located in lysosomes.

Acid Phosphatase↗
PubMed1979

A patient with Cronkhite-Canada syndrome, myxedema and muscle atrophy.

A case of Cronkhite-Canada syndrome is presented. The patient had alopecia, onychodystrophy and gastrointestinal polyposis, mainly in the stomach and duodenum, with transient diarrhea and hypoproteinemia. Marked atrophy and weakness of the shoulder girdle muscles due to myopathy were also present. In addition she had primary hypothyroidism. The outcome of the disease is usually fatal within months, but so far our patient is alive four years after the onset of symptoms. The pathological changes, pathophysiology, symptoms, course and treatment of this rare disorder of unknown etiology are discussed.

Aged↗
PubMed1979

Muscle atrophy in rats following denervation, casting, inflammation, and tenotomy.

One week after unilateral denervation, tenotomy, casting, or joint inflammation, skeletal muscles of adult female Wistar rats were studied to determine the effect of these processes on muscle weights and fiber diameters of the soleus, the red and white regions of the plantaris, plus muscle weights and protein content of the gastrocnemius. All atrophic processes caused greater weight loss of the soleus than of the plantaris or gastrocnemiums. Within the soleus and plantaris muscles, the type-I fiber atrophy was equal to the type-II fiber atrophy except for the white region of the plantaris following tenotomy, where the wasting of the type-I fiber was greater than that of type II. This study also demonstrated that denervation, tenotomy, casting, and inflammation resulted in a greater loss of myofibrillar proteins (content and absolute amounts) than of sarcoplasmic and stromal proteins. Denervation generally was found to have the greatest effect on the parameters evaluated. The findings are consistent with the hypothesis that slow muscle is more dependent than fast muscle on neuronal control, and that nerve controls muscle through the dual role of impulse activity and axoplasmic flow.

Animals↗
PubMed1979

Work capacity, contractile protein and quantitative electromyogram (EMG) changes following exercise or nandrolone decanoate treatment in experimentally induced muscle disuse atrophy in rats.

Anabolic steroid administration and planned exercise have been the two main methods applied to improve the function and morphology of atrophied muscle tissue. The effects of these two factors-specifically nandrolone decanoate administration and exercise by swimming on muscle weight, EMG activity, work capacity and on contractile protein content of rat gastrocnemius muscle, following experimentally induced atrophy by immobilization, were investigated. The results appear to support the conclusion that although both types of treatment obtain significant positive results exercise acts more effectively than the anabolic steroid in this respect.

Actomyosin↗
PubMed1978

Regrowth of atrophied skeletal muscle in adult rats after ending immobilization.

The recovery time course of muscle atrophied by immobilization was followed after removal of hindlimb casts from adult female rats. Increases of only 9% in body weight, 4% in gastrocnemius weight, and 10% in soleus weight occurred in controls during the 78-day duration of the experiment. There were no increases in the amounts of total protein or of citrate synthase activities in gastrocnemius or soleus during the first 3 days after removal of hindlimb casts; thereafter, there were increases in these paramters. Citrate synthase activities per mg of gastrocnemius protein were significantly higher at the 16th and 50th day of recovery. No significant differences for citrate synthase activity per mg of soleus occurred during recovery. Until the 50th day of recovery, no significant differences for total protein in soleus and for total protein and wet weight of gastrocnemius were observed between control and recovery values. However, the wet weight of the soleus returned rapidly during recovery and was not significantly different from control during recovery.

Aging↗
PubMed1979

Sulphur and phosphorus content in relation to fibre composition and atrophy of skeletal muscle in patients with Parkinson's disease.

Seventeen patients with Parkinson's disease have been compared with 8 normal individuals by biopsy of either the biceps brachii or quadriceps femoris muscles. All biopsies were investigated by enzyme histochemistry. With 13 patients, as well as all controls, scanning electron microscopy with X-ray microanalysis was employed on cryo-sections adjacent to those prepared for light microscopy. Thus, the elemental composition of single muscle fibres was obtained and could be related to histochemical fibre types. Fibre type analysis on the diseased material, based on differential stainability for alkali- and acid-stable ATPase, showed a normal type I and type IIA fibre frequency. A mild type IIB dominance at the expense of type IIA fibres was regarded as a significant deviation from normal. A slight to moderate muscle atrophy affected type IIB fibres almost exclusively. Normal content of sulphur and phosphorus was detected in type I and type IIA Fibres but a lowered sulphur content was obvious in type IIB fibres, especially in the atrophic ones, which also exhibited an increase in phosphorus content. The shift in fibre composition from IIA to IIB, the type IIB fibre atrophy and the change in sulphur and phosphorus content of type IIB fibres are interpreted as signs of a disuse which preferentially affects fast twitch type IIB motor units. These presumably have the highest threshold for activation under pathological conditions characterized by increased muscular tone and difficulties in the performance of rapid and strong voluntary movements.

Adenosine Triphosphatases↗
PubMed1979

Gyrate atrophy of the choroid and retina with hyperornithinemia: tubular aggregates and type 2 fiber atrophy in muscle.

We studied 21 patients with gyrate atrophy of the choroid and retina and hyperornithinemia. Although the patients were not weak, type 2 muscle fibers were almost universally atrophic and had tubular aggregates. Gyrate atrophy is the first disease in which females are shown to have tubular aggregates; the sexes were affected equally. In gyrate atrophy the number of type 2 fibers decreases with age. The muscle and eye changes are probably related to abnormal creatine synthesis, caused, in gyrate atrophy, by the increased body pool of ornithine; muscle abnormalities may also be present in other tapetoretinal dystrophies.

Adolescent↗
PubMedDate not supplied

Fine structure of muscle in human disuse atrophy: significance of proximal muscle involvement in muscle disorders.

The universal occurrence of weakness of skeletal musculature on disuse, however produced, and the paucity of published reports on the fine structural changes in human disuse atrophy, prompted the present investigation. The quadriceps muscle of a leg immobilized in plaster cast (for fracture) and of the opposite non-immobilized limb was biopsied in four adult males, after periods of immobilization from 50 to 75 days. These 8 muscle specimens were examined for histopathological changes, and muscle fibre diameters were measured by micrometry from paraffin sections. The histograms revealed a larger proportion of small fibres (less than 20 micron) and a smaller proportion of large fibres (greater than 40 micron) in the immobilized limb compared to the opposite. Thus, light microscopy showed only atrophic changes. This was confirmed by electronmicroscopy, where atrophy of few to several muscle fibres was seen in the form of loss of myofibrils, collapse and folding of the basement membrane and prominence of glycogen or muscle nuclei. The atrophic change was more severe in the immobilized limbs, but it was also noticeable in all the non-immobilized limbs. Degenerative changes, especially disorganization and breakdown of myofibrils, and fragmentation of plasma membrane, were also seen in occasional atrophied muscle fibres, again more frequently in the immobilized limb. Lipofuscin was often found accumulated in muscle fibres and occasionally in endothelial cells of intramuscular blood vessels; the latter showed prominent pinocytotic vesicles or thickened basement membrane. It is concluded that both atrophy and degeneration of fibres of proximal muscles can occur as non-specific consequences of disuse of the limb in man, that degeneration is a latter and more severe change, that muscles even of the non-immobilized leg are subjected to disuse atrophy during bed-rest, and that the proximal muscles in man seem to have a natural susceptibility to atrophy and degeneration in any muscular disorders.

Adult↗