RESUMO
Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain accompanied by fatigue and muscle atrophy. Although its etiology is not known, studies have shown that FM patients exhibit altered function of the sympathetic nervous system (SNS), which regulates nociception and muscle plasticity. Nevertheless, the precise SNS-mediated mechanisms governing hyperalgesia and skeletal muscle atrophy in FM remain unclear. Thus, we employed two distinct FM-like pain models, involving intramuscular injections of acidic saline (pH 4.0) or carrageenan in prepubertal female rats, and evaluated the catecholamine content, adrenergic signaling and overall muscle proteolysis. Subsequently, we assessed the contribution of the SNS to the development of hyperalgesia and muscle atrophy in acidic saline-injected rats treated with clenbuterol (a selective ß2-adrenergic receptor agonist) and in animals maintained under baseline conditions and subjected to epinephrine depletion through adrenodemedullation (ADM). Seven days after inducing an FM-like model with acidic saline or carrageenan, we observed widespread mechanical hyperalgesia along with loss of strength and/or muscle mass. These changes were associated with reduced catecholamine content, suggesting a common underlying mechanism. Notably, treatment with a ß2-agonist alleviated hyperalgesia and prevented muscle atrophy in acidic saline-induced FM-like pain, while epinephrine depletion induced mechanical hyperalgesia and increased muscle proteolysis in animals under baseline conditions. Together, the results suggest that reduced sympathetic activity is involved in the development of pain and muscle atrophy in the murine model of FM analyzed.
Assuntos
Clembuterol , Modelos Animais de Doenças , Fibromialgia , Hiperalgesia , Atrofia Muscular , Sistema Nervoso Simpático , Animais , Feminino , Fibromialgia/patologia , Fibromialgia/fisiopatologia , Atrofia Muscular/patologia , Atrofia Muscular/fisiopatologia , Hiperalgesia/fisiopatologia , Hiperalgesia/patologia , Sistema Nervoso Simpático/fisiopatologia , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/patologia , Clembuterol/farmacologia , Ratos , Carragenina/toxicidade , Ratos Sprague-Dawley , Dor/patologia , Dor/fisiopatologia , Epinefrina , Músculo Esquelético/patologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiopatologia , Catecolaminas/metabolismo , Agonistas Adrenérgicos beta/farmacologiaRESUMO
Physical exercise has profound effects on quality of life and susceptibility to chronic disease; however, the regulation of skeletal muscle function at the molecular level after exercise remains unclear. We tested the hypothesis that the benefits of exercise on muscle function are linked partly to microtraumatic events that result in accumulation of circulating heme. Effective metabolism of heme is controlled by Heme Oxygenase-1 (HO-1, Hmox1), and we find that mouse skeletal muscle-specific HO-1 deletion (Tam-Cre-HSA-Hmox1fl/fl) shifts the proportion of muscle fibers from type IIA to type IIB concomitant with a disruption in mitochondrial content and function. In addition to a significant impairment in running performance and response to exercise training, Tam-Cre-HSA-Hmox1fl/fl mice show remarkable muscle atrophy compared to Hmox1fl/fl controls. Collectively, these data define a role for heme and HO-1 as central regulators in the physiologic response of skeletal muscle to exercise.
Assuntos
Heme Oxigenase-1/genética , Heme/metabolismo , Proteínas de Membrana/genética , Fibras Musculares Esqueléticas/metabolismo , Atrofia Muscular/genética , Condicionamento Físico Animal/fisiologia , 5-Aminolevulinato Sintetase/genética , 5-Aminolevulinato Sintetase/metabolismo , Animais , Ferroquelatase/genética , Ferroquelatase/metabolismo , Regulação da Expressão Gênica , Heme Oxigenase-1/deficiência , Isoenzimas/genética , Isoenzimas/metabolismo , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Masculino , Proteínas de Membrana/deficiência , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Atrofia Muscular/metabolismo , Atrofia Muscular/fisiopatologia , Proteína MyoD/genética , Proteína MyoD/metabolismo , Fator de Transcrição PAX7/genética , Fator de Transcrição PAX7/metabolismo , Transdução de Sinais , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Cerebellofaciodental syndrome is characterized by facial dysmorphisms, intellectual disability, cerebellar hypoplasia, and dental anomalies. It is an autosomal-recessive condition described in 2015 caused by pathogenic variants in BRF1. Here, we report a Brazilian patient who faced a diagnostic challenge beginning at 11 months of age. Fortunately, whole-exome sequencing (WES) was performed, detecting the BRF1 variants NM_001519.3:c.1649delG:p.(Gly550Alafs*36) and c.421C>T:p.(Arg141Cys) in compound heterozygosity, thus finally achieving a diagnosis of cerebellofaciodental syndrome. The patient is currently 25 years old and is the oldest patient yet reported. The clinical report and a review of published cases are presented. Atlanto-occipital fusion, a reduced foramen magnum and basilar invagination leading to compression of the medulla-spinal cord transition are skeletal findings not reported in previous cases. The description of syndromes with dental findings shows that such anomalies can be an important clue to relevant differential diagnoses. The cooperation of groups from different international centers made possible the resolution of this and other cases and is one of the strategies to bring medical advances to developing countries, where many patients with rare diseases are difficult to diagnose definitively.
Assuntos
Anormalidades Múltiplas/genética , Cerebelo/anormalidades , Anormalidades Craniofaciais/genética , Deficiência Intelectual/genética , Atrofia Muscular/genética , Malformações do Sistema Nervoso/genética , Fatores Associados à Proteína de Ligação a TATA/genética , Anormalidades Dentárias/genética , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/fisiopatologia , Adulto , Brasil/epidemiologia , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Criança , Pré-Escolar , Anormalidades Craniofaciais/diagnóstico por imagem , Anormalidades Craniofaciais/fisiopatologia , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/fisiopatologia , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/fisiopatologia , Masculino , Atrofia Muscular/diagnóstico por imagem , Atrofia Muscular/fisiopatologia , Malformações do Sistema Nervoso/diagnóstico por imagem , Malformações do Sistema Nervoso/fisiopatologia , Anormalidades Dentárias/diagnóstico por imagem , Anormalidades Dentárias/fisiopatologia , Sequenciamento do ExomaRESUMO
Sarcopenia is a condition of muscle dysfunction, commonly associated with chronic liver disease (CLD), characterized by a decline in muscle strength, the activation of the ubiquitin-proteasome system (UPS), and oxidative stress. We recently described a murine model of CLD-induced sarcopenia by intake of hepatotoxin 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), which presents an increase in plasma bile acids (BA). BA induced skeletal muscle atrophy through a mechanism dependent on the Takeda G protein-coupled receptor 5 (TGR5) receptor. In the present study, we evaluated the role of TGR5 signaling in the development of sarcopenia using a model of DDC-induced CLD in C57BL6 wild-type (WT) mice and mice deficient in TGR5 expression (TGR5-/- mice). The results indicate that the decline in muscle function and contractibility induced by the DDC diet is dependent on TGR5 expression. TGR5 dependence was also observed for the decrease in fiber diameter and sarcomeric proteins, as well as for the fast-to-slow shift in muscle fiber type. UPS overactivation, indicated by increased atrogin-1/MAFbx (atrogin-1) and muscle RING-finger protein-1 (MuRF-1) protein levels and oxidative stress, was abolished in tibialis anterior muscles from TGR5-/- mice. Our results collectively suggest that all sarcopenia features induced by the DDC-supplemented diet in mice are dependent on TGR5 receptor expression.
Assuntos
Ácidos e Sais Biliares/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Sarcopenia/metabolismo , Animais , Ácidos e Sais Biliares/sangue , Doença Hepática Induzida por Substâncias e Drogas/complicações , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Crônica , Expressão Gênica , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora/fisiologia , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Atrofia Muscular/genética , Atrofia Muscular/metabolismo , Atrofia Muscular/fisiopatologia , Piridinas , Receptores Acoplados a Proteínas G/genética , Sarcopenia/induzido quimicamente , Sarcopenia/complicaçõesRESUMO
Therapeutic immobilization is a common treatment for the locomotor system; however, it causes loss of muscle due to disuse, leading to protein degradation and generating atrophy of muscle cells, ultimately changing functionality. In this sense, it is important for remobilization to be initiated early and performed with appropriate therapeutic strategies that enable tissue and functional recovery. One method of remobilization is physical exercise, among which whole body vibration (WBV) has been highlighted and mainly applied in people with reduced mobility. However, there are gaps on the morphological effects WBV has on muscle tissue, so in this study we analyzed the histomorphometry of the tibialis anterior muscle (TA) of Wistar rats remobilized using WBV. For the experiment, 32 male Wistar rats were used and divided into four groups (n = 8/group). Groups consisted of: control (CG), immobilized (IG), immobilized and remobilized freely (FG), and immobilized and remobilized with WBV (WG). After the experimental period, the TA was collected and processed for analysis in light microscopy. When compared to the control group, significant morphological changes were observed, which characterize muscle atrophy and reduction of all histomorphometric parameters of the TA of the immobilized animals. Remobilized animals showed improvement in all parameters, and the WBV was not different from the free remobilization, except for the reduction of central nuclei, which can be related to acceleration of the process of tissue regeneration. Thus, we can conclude that the WBV can have an impact on the acceleration of the muscle regenerative process, and may be beneficial in people with reduced mobility.
Assuntos
Imobilização/efeitos adversos , Músculo Esquelético/fisiopatologia , Atrofia Muscular/terapia , Recuperação de Função Fisiológica/fisiologia , Vibração/uso terapêutico , Animais , Eletromiografia , Masculino , Atrofia Muscular/etiologia , Atrofia Muscular/fisiopatologia , Ratos , Ratos WistarRESUMO
OBJECTIVE: The aim of this study was to evaluate whether low skeletal muscle mass index (SMI) and low phase angle (PhA) are associated with demographic, clinical, lifestyle, and nutritional status in patients dependent on alcohol and other substances. METHODS: We prospectively included 63 individuals dependent on alcohol and other substances and 71 age- and sex-matched healthy controls. Body composition was assessed by bioelectrical impedance analysis. Subjective global assessment was used to evaluate malnutrition. All included participants underwent a psychiatric evaluation, including the administration of the Mini-International Neuropsychiatric Interview. Univariate and multivariate analysis were performed to evaluate associations between low skeletal muscle mass index (SMI) and low phase angle (PhA) and nutritional, lifestyle, and alcohol use and cocaine/crack use variables, controlling for sex and age. RESULTS: Low SMI and low PhA were identified in 11.1% and 44.5% of the substance dependents, respectively. Low midarm muscle circumference (r = 0.58; P < 0.001), low midarm muscle area (r = 051; P < 0.001), and reduced PhA (r = 0.59; P < 0.001) were positively correlated with low SMI. Multivariate analysis showed that heavy alcohol consumption (≥80 g·d· ≥5 y-1; odds ratio [OR], 2.33; 95% confidence interval [CI], 1.12-4.84; P = 0.02) and sedentary lifestyle (OR, 4.39; 95% CI, 1.29-14.89; P = 0.02) were independently associated with reduced SMI. Low PhA was independently associated with heavy alcohol consumption (OR, 3.64; 95% CI, 1.62-8.15; P = 0.002) and cocaine or crack use (OR, 3.97; 95% CI, 1.05-15.11; P = 0.04) in multivariate analysis. CONCLUSIONS: Low SMI and low PhA are independently associated with heavy alcohol consumption. Low PhA is independently associated with cocaine or crack use.
Assuntos
Alcoolismo/fisiopatologia , Composição Corporal , Impedância Elétrica , Músculo Esquelético/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Adulto , Alcoolismo/complicações , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Desnutrição/etiologia , Desnutrição/fisiopatologia , Pessoa de Meia-Idade , Atrofia Muscular/etiologia , Atrofia Muscular/fisiopatologia , Estado Nutricional , Razão de Chances , Estudos Prospectivos , Comportamento Sedentário , Transtornos Relacionados ao Uso de Substâncias/complicaçõesRESUMO
Knee osteoarthritis (KOA) is associated with muscle weakness, but it is unclear which structures are involved in the muscle changes. This study assessed morphological alterations and the expression of genes and proteins linked to muscular atrophy and neuromuscular junctions (NMJs) in KOA, induced by anterior cruciate ligament transection (ACLT) in rats. Two groups of rats were assessed: control (without intervention) and KOA (ACLT surgery in the right knee). After 8 weeks, quadriceps, tibialis anterior (TA) and gastrocnemius muscles were analyzed (area of muscle fibers, NMJ, gene and protein expression). KOA group showed atrophy in quadriceps (15.7%) and TA (33%), with an increase in atrogin-1 and muscle RING-finger protein-1 (MuRF-1). KOA group showed quadriceps NMJ remodeling (reduction area and perimeter) and decrease in NMJ diameter in TA muscle. The expression of nicotinic acetylcholine receptor (nAChR) γ-nAChR increased and that of α-nAChR and muscle specific tyrosine kinase (MuSK) declined in the quadriceps, with a decrease in ε-nAChR in TA. MuRF-1 protein expression increased in quadriceps and TA, with no changes in neural cell adhesion molecule (NCAM). In conclusion, ACLT-induced KOA promotes NMJ remodeling and atrophy in quadriceps and TA muscles, associated with inflammatory signs and changes in muscle gene and protein expression.
Assuntos
Proteínas Musculares/genética , Músculo Esquelético/metabolismo , Atrofia Muscular/genética , Junção Neuromuscular/metabolismo , Osteoartrite do Joelho/genética , Músculo Quadríceps/metabolismo , Animais , Ligamento Cruzado Anterior/fisiopatologia , Ligamento Cruzado Anterior/cirurgia , Expressão Gênica , Proteínas Musculares/metabolismo , Debilidade Muscular/genética , Debilidade Muscular/metabolismo , Debilidade Muscular/fisiopatologia , Músculo Esquelético/fisiopatologia , Atrofia Muscular/metabolismo , Atrofia Muscular/fisiopatologia , Junção Neuromuscular/fisiopatologia , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/fisiopatologia , Músculo Quadríceps/fisiopatologia , Ratos Wistar , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Proteínas Ligases SKP Culina F-Box/genética , Proteínas Ligases SKP Culina F-Box/metabolismo , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
STUDY DESIGN: This work is a systematic review with meta-analysis OBJECTIVE: Evaluate the effect of electrical stimulation (ES) on skeletal muscle volume and spasticity in individuals with spinal cord injury (SCI). SETTING: University of Brasilia, Brazil METHODS: Searches were conducted of the Cochrane Library, MEDLINE, CINAHL, PEDro, PsycINFO and EMBASE electronic databases for relevant articles published up to June 2018. No restrictions were imposed regarding the year of publication. The inclusion criteria were randomized controlled trials involving adults with SCI comparing ES to an active or passive control. Two independent reviewers extracted the data from the selected studies and methodological quality was assessed using the PEDro scale. RESULTS: The initial search led to the retrieval of 164 studies, seven of which met the eligibility criteria, but only six were included in the meta-analysis. The six studies comprised 104 patients with complete or incomplete SCI. In the two studies that investigated the use of ES on muscle volume of the lower limbs, the overall effect was statistically significant in patients with acute SCI (mean difference: 0.86; 95% CI: 0.04 to 1.69; p < 0.04). Among the four studies that examined the use of ES for spasticity of the lower limb, the overall effect was non-significant (mean difference: 0.55; 95% CI: -0.31 to 1.41; p = 0.21). CONCLUSIONS: Electrical stimulation was found to be an effective method for increasing muscle volume in SCI patients, but had no effect on spasticity. Further investigation of the effect of ES on spasticity in SCI is needed.
Assuntos
Terapia por Estimulação Elétrica , Espasticidade Muscular/terapia , Atrofia Muscular/terapia , Traumatismos da Medula Espinal/terapia , Humanos , Espasticidade Muscular/fisiopatologia , Atrofia Muscular/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
Due to the difficulty of performing research protocols that reproduce human skeletal muscle disuse conditions, an experimental animal model of "hindlimb suspension" (or hindlimb unloading) was developed. This method was created in the 1970s and utilizes rats and mice to mimic space flight and bed rest in humans. It provides an alternative to investigate mechanisms associated with skeletal muscle mass loss and interventions designed to attenuate atrophy induced by hindlimb unloading. The mentioned protocol also allows investigating quality of bones and changes in several physiological parameters such as blood pressure, heart rate, plasma or tissue lipid composition, and glycemia.
Assuntos
Atrofia/sangue , Elevação dos Membros Posteriores/métodos , Músculo Esquelético/fisiopatologia , Atrofia Muscular/sangue , Animais , Atrofia/genética , Atrofia/fisiopatologia , Pressão Sanguínea , Humanos , Lipídeos/sangue , Músculo Esquelético/metabolismo , Atrofia Muscular/fisiopatologia , Ratos , RoedoresRESUMO
PURPOSE: To evaluate the association between the rectus femoris cross-sectional area (RFCSA) and the muscular strength obtained at the bedside in patients forwarded to the intensive care unit (ICU) for severe sepsis and septic shock. METHODS: An observational study of prospective cohort. RFCSA was assessed by ultrasound on the following day of the ICU admission and monitored during hospitalization. The patients performed clinical tests of muscle strength (Medical Research Council (MRC) scale and handgrip dynamometry), when they could understand the verbal commands of the examiners. RESULTS: In 37 patients hospitalized for sepsis there was a significant decline in RFCSA of 5.18 (4.49-5.96) cm on the 2nd day of ICU for 4.37 (3.71-5.02) cm at hospital discharge. Differently, the handgrip strength showed an increase from the awakening of 12.00 (7.00-20.00) Kgf to 19.00 (14.00-26.00) Kgf until hospital discharge. Patients in mechanical ventilation had a greater tendency to decline in the RFCSA compared with patients who did not receive mechanical ventilation, however without being significant (Pâ=â0.08). There was a negative association between RFCSA delta (2nd day of ICU-ICU discharge) and handgrip strength (râ=â0.51, Pâ<â0.05), and a male and Sepsis-related Organ Failure Assessment score positive association with the RFCSA delta. CONCLUSION: There was an association of RFCSA with clinical muscle strength tests. In addition, it has been shown that sepsis can lead to short-term muscle degradation, regardless of whether they are submitted to mechanical ventilation or not.