The maintenance of skeletal muscle quality involves various signal pathways that interact with each other. Under normal physiological conditions, these intersecting signal pathways regulate and coordinate the hypertrophy and atrophy of skeletal muscles, balancing the protein synthesis and degradation of muscle. When the total rate of protein synthesis exceeds that of protein degradation, the muscle gradually becomes enlarged, while when the total rate of protein synthesis is lower than that of protein degradation, the muscle shrinks. Myocyte atrophy mainly involves two protein degradation pathways, namely ubiquitin-proteasome and autophagy-lysosome. Protein degradation pathway is activated during muscle atrophy, resulting in the loss of muscle mass. Muscle atrophy can occur under various conditions such as malnutrition, aging and cachexia. Skeletal muscle atrophy caused by orthopedic diseases mainly includes disuse muscular atrophy caused by fracture and denervation muscular atrophy. The signal pathways that control and coordinate protein synthesis and degradation in skeletal muscle include insulin-like growth factor 1 (IGF1)-Akt-mammalian target of rapamycin (mTOR), myostatin-activin A-Smad, G protein α inhibitory peptide 2 (Gαi2)-PKC, nuclear factor κB (NF-κB), ectodysplasin A2 receptor (EDA2R)-NF-κB inducing kinase (NIK) and mitogen-activated protein kinase (MAPK) pathways. This paper provides a comprehensive review of the protein degradation pathways in skeletal muscle atrophy and the associated signal pathways regulating protein degradation in muscular atrophy.
Humans ; Muscular Atrophy/etiology* ; Muscle, Skeletal/pathology* ; Signal Transduction ; Animals ; Insulin-Like Growth Factor I/metabolism* ; Myostatin/physiology* ; TOR Serine-Threonine Kinases/metabolism* ; Autophagy/physiology* ; NF-kappa B/metabolism* ; Proteolysis ; Proteasome Endopeptidase Complex/physiology*

Spinal and bulbar muscular atrophy (SBMA) is a rare X-linked motor neuron disease with significant phenotypic viability. Here, we present a genetically identified SBMA family without bulbar paralysis or androgen insensitivity. All four male patients presented with progressive lower motor neuron paralysis in all limbs, with distal extremities more dominant. None of them had bulbar palsy or androgen insensitivity. A consistently mild elevated blood creatine phosphokinase (CPK) levels were detected in all patients and the EMG showed a chronic neurogenic damage. Muscle biopsy of propositus indicated a typical neurogenic amyotrophy. Genetic testing for SMA of mutation in SMN1 was negative, while for SBMA of androgen receptor showed the increased CAG repeat in exon 1, suggesting that although bulbar symptoms and androgen insensitivity are characteristic symptoms of SBMA, they are not obligatory for the diagnosis. In adult males with a chronic motor neuron syndrome without upper motor neuron signs, even in absence of the classical features of androgen insensitivity or bulbar findings, genetic testing for SBMA should be strongly considered.
Adult ; Bulbo-Spinal Atrophy, X-Linked ; complications ; diagnosis ; genetics ; Creatine Kinase ; blood ; Genetic Testing ; Humans ; Male ; Motor Neurons ; pathology ; Muscular Atrophy ; etiology ; Mutation ; genetics ; Paralysis ; diagnosis ; etiology ; Pedigree ; Receptors, Androgen ; genetics

OBJECTIVESTo compare the paravertebral muscle (such as multifidus, erector spinae, psoas muscle) changes between the patients with degenerative lumbar instability and normal person by MRI and to observe the degeneration of paravertebral muscles. To analyze the relationship between paravertebral muscle degeneration and lumbar curvature of degenerative lumbar instability.

METHODSSixty patients with degenerative lumbar instability were retrospectively enrolled from December 2011 to July 2013 as degeneration group, meanwhile 60 health persons with no degenerative lumbar instability were selected as control group. No significant differences were found in the gender, age and body mass index between the two groups. The cross-sectional area(CSA) and percentage of fat infiltration area (FIA) of the paravertebral muscles at the L4-S1 levels were measured using T2-weighted axial MRI and Image J soft ware. And the lumbar curvature(expressed as lumbar lordosis angle) of all the patients in lumbar X-ray were measured in the two groups. The measured data were analyzed with independent samples t-test.

RESULTSThe difference of multifidus cross-sectional area and the percentage of fat infiltration in the patients of degenerative lumbar instability at the L4-L5, L5-S1 level, compared with the control group, was statistically significant (t = 2.768, t = 6.216, P < 0.05). Between the two groups, the percentage of fatty infiltration in erector spinae showed significant differences (t = 5.862, P < 0.05). The cross-sectional area of erector spinae and the degeneration of the psoas muscle between the two groups was not statistically significant. The lumbar lordsis angle in the patients with degenerative lumbar instability was (43.9 ± 15.6)°, which was higher than the (39.3 ± 14.2)° in control group (t = 2.915, P < 0.05).

CONCLUSIONSCompared with the control group, patients with degenerative lumbar instability exists erector spinae and multifidus muscle degeneration, and erector spinae is more obvious. The degeneration among psoas muscle, erector spinae and multifidus muscle are inconsistent, which may be related to the increasing of the lumbar lordosis angle in the patients with degenerative lumbar instability.

Aged ; Case-Control Studies ; Female ; Humans ; Joint Instability ; diagnosis ; etiology ; pathology ; Lumbosacral Region ; physiopathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Muscle, Skeletal ; pathology ; Muscular Atrophy ; complications ; diagnosis ; pathology

Angiotensin II ; metabolism ; Animals ; Male ; Muscle, Skeletal ; Muscular Atrophy ; etiology ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley

PURPOSE: The purpose of this study was to determine the effect of dehydroepiandrosterone (DHEA) on recovery of muscle atrophy induced by Parkinson's disease. METHODS: The rat model was established by direct injection of 6-hydroxydopamine (6-OHDA, 20 microg) into the left striatum using stereotaxic surgery. Rats were divided into two groups; the Parkinson's disease group with vehicle treatment (Vehicle; n=12) or DHEA treatment group (DHEA; n=22). DHEA or vehicle was administrated intraperitoneally daily at a dose of 0.34 mmol/kg for 21 days. At 22-days after DHEA treatment, soleus, plantaris, and striatum were dissected. RESULTS: The DHEA group showed significant increase (p<.01) in the number of tyrosine hydroxylase (TH) positive neurons in the lesioned side substantia nigra compared to the vehicle group. Weights and Type I fiber cross-sectional areas of the contralateral soleus of the DHEA group were significantly greater than those of the vehicle group (p=.02, p=.00). Moreover, extracellular signal-regulated kinase (ERK) phosphorylation significantly decreased in the lesioned striatum, but was recovered with DHEA and also in the contralateral soleus muscle, Akt and ERK phosphorylation recovered significantly and the expression level of myosin heavy chain also recovered by DHEA treatment. CONCLUSION: Our results suggest that DHEA treatment recovers Parkinson's disease induced contralateral soleus muscle atrophy through Akt and ERK phosphorylation.
Animals ; Corpus Striatum/drug effects/metabolism ; Dehydroepiandrosterone/*pharmacology/therapeutic use ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Male ; Muscle Fibers, Slow-Twitch/drug effects ; Muscle, Skeletal/drug effects/metabolism ; Muscular Atrophy/drug therapy/*etiology/*pathology ; Myosins/metabolism ; Neurons/drug effects/enzymology ; Oxidopamine/toxicity ; Parkinson Disease, Secondary/*chemically induced/*complications ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Rats, Sprague-Dawley ; Tyrosine 3-Monooxygenase/metabolism

PURPOSE: The purpose of this study was to examine the effect of DHEA (Dehydroepiandrosterone) on muscle weight and Type I and II fiber cross-sectional area of affected and unaffected hindlimb muscles in rats with neuropathic pain induced by unilateral peripheral nerve injury. METHODS: Neuropathic pain was induced by ligation and cutting of the left L5 spinal nerve. Adult male Sprague-Dawley rats were randomly assigned to one of two groups: The DHEA group (n=10) had DHEA injections daily for 14 days, and the Vehicle group (n=10) had vehicle injections daily for 14 days. Withdrawal threshold, body weight, food intake and activity were measured every day. At 15 days all rats were anesthetized and soleus, plantaris and gastrocnemius muscles were dissected from the both hindlimbs. Body weight, food intake, activity, muscle weight and Type I, II fiber cross-sectional area of the dissected muscles were measured. RESULTS: The DHEA group showed significant increases (p<.05), as compared to the vehicle group for muscle weight of the unaffected plantaris, and in Type II fiber cross-sectional area of the gastrocnemius muscle. The DHEA group demonstrated a higher pain threshold than the vehicle group whereas total diet intake and activity score were not significantly different between the two groups. CONCLUSION: DHEA administration for 14 days attenuates unaffected plantaris and gastrocnemius muscle atrophy.
Animals ; Body Weight ; Dehydroepiandrosterone/*administration & dosage ; Disease Models, Animal ; Eating/drug effects ; *Hindlimb ; Male ; Muscle Fibers, Skeletal/*drug effects/pathology ; Muscle, Skeletal/drug effects ; Muscular Atrophy/*drug therapy ; Pain/etiology ; Pain Measurement ; Peripheral Nerves/*injuries ; Rats ; Rats, Sprague-Dawley

PURPOSE: The purpose of this study was to identify muscle atrophy in critically ill patients on ventilators. A comparison was made between limb circumferences and muscle areas on the day of admission to an intensive care unit (ICU) and on the 8th day after admission. METHODS: The data were collected from 30 critically ill patients using ventilators at S hospital ICU in Seoul during the period from October 2005 to April 2006. Limb circumferences and skinfold thickness were measured on the day of admission and on the 8th day after admission to the ICU. Limb circumferences and skinfold thickness were measured on the right mid-arm, right mid-thigh, and right mid-calf using a measuring tape and a skinfold calipers. Limb muscle areas were calculated by an equation after measuring limb circumferences and skinfold thickness. The data were analyzed by paired t-test and independent t-test. RESULTS: 1) Mid-arm circumference, mid-thigh circumference and mid-calf circumference on the 8th day after admission to the ICU were significantly less than those on the day of admission to the ICU, 2) Mid-arm muscle area, mid-thigh muscle area and mid-calf muscle area on the 8th day after admission to the ICU were significantly less than those on the day of admission to the ICU, 3) Steroid and vecuronium medication didn't affect changes in limb circumferences (mid-arm, mid-thigh, mid-calf) and muscle areas (mid-arm, mid-thigh, mid-calf) on the 8th day after admission to the ICU compared to the day of admission. CONCLUSION: Limb muscle atrophy may occur on the 8th day after admission to the ICU in critically ill patients using ventilator.
Adult ; Aged ; Critical Illness ; Data Interpretation, Statistical ; Extremities/physiology ; Female ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Muscle, Skeletal/pathology ; Muscular Atrophy/*diagnosis/etiology/therapy ; Skinfold Thickness ; Steroids/administration & dosage ; *Ventilators, Mechanical

PURPOSE: The purpose of this study was to examine the effects of daily exercise before steroid treatment on mass, the type I and II fiber cross-sectional area, and myofibrillar protein content of hindlimb muscles in a rat model. METHOD: Adult male Sprague-Dawley rats were randomly assigned to one of three groups: a control group(n=10) that had a normal saline injection for 7days, a steroid group(n=10) that had a steroid injection for 7days, and an exercise-steroid group(n=10) that ran on the treadmill for 7days before a steroid treatment. Body weight and food intake were measured every day. At 15 days all rats were anesthetized and the soleus, plantaris and gastrocnemius muscles were dissected. RESULT: The exercise-steroid group showed significant increases as compared with the steroid group in body weight, muscle weight of the soleus and gastrocnemius, type II muscle fiber cross-sectional area of plantaris, and myofibrillar protein content of the soleus, plantaris, and gastrocnemius. As compared with the control group, the steroid group showed significant decreases in body weight and diet intake, muscle weight, the type II fiber cross-sectional area and myofibrillar protein content of the soleus, plantaris, and gastrocnemius muscles. CONCLUSION: Daily exercise before steroid treatment attenuates hindlimb muscle atrophy, with type II muscle changes more apparent than type I muscle changes.
Animals ; Body Weight ; Combined Modality Therapy ; Dexamethasone/*therapeutic use ; Disease Models, Animal ; *Exercise Therapy ; Hindlimb ; Male ; Muscle Contraction/drug effects ; Muscle Fibers, Skeletal/*drug effects/physiology ; Muscle, Skeletal/*drug effects/physiology ; Muscular Atrophy/etiology/pathology/*therapy ; Organ Size ; Rats ; Rats, Sprague-Dawley

In this study, we compared the paramedian interfascial approach (PIA) and the traditional midline approach (MA) for lumbar fusion to determine which approach resulted in the least amount of postoperative back muscle atrophy. We performed unilateral transforaminal posterior lumbar interbody fusion via MA on the symptomatic side and pedicle screw fixation via PIA on the other side in the same patient. We evaluated the damage to the paraspinal muscle after MA and PIA by measuring the preoperative and postoperative paraspinal muscle volume in 26 patients. The preoperative and postoperative cross-sectional area, thickness, and width of the multifidus muscle were measured by computed tomography. The degree of postoperative paraspinal muscle atrophy was significantly greater on the MA side than on the contralateral PIA side (-20.7% and -4.8%, respectively, p<0.01). In conclusion, the PIA for lumbar fusion yielded successful outcomes for the preservation of paraspinal muscle in these 26 patients. We suggest that the success of PIA is due to less manipulation and retraction of the paraspinal muscle and further studies on this technique may help confirm whether less muscle injury has positive effects on the long-term clinical outcome.
Adult ; Aged ; *Bone Screws ; Female ; Humans ; Lumbar Vertebrae/*surgery ; Male ; Middle Aged ; Muscle, Skeletal/pathology ; Muscular Atrophy/etiology/pathology ; Postoperative Complications/etiology/pathology ; Reproducibility of Results ; Retrospective Studies ; Spinal Fusion/adverse effects/instrumentation/*methods ; Tomography, X-Ray Computed

PURPOSE: The purpose of this study was to examine the effects of cerebral ischemia on Type I(soleus) and Type II(plantaris, gastrocnemius) muscles, and to determine the effects of isometric contraction training by electrostimulation on Type I andII muscles in cerebral ischemia model rats. METHOD: Twenty-five male Sprague-Dawley rats were randomly divided into four groups: ST(stroke), STES(stroke+electrostimulation), SH(sham) and SHES (sham+electrostimulation). The ST and STES groups received a transient right middle cerebral artery occlusion operation. The SH and SHES groups received a sham operation. The STES and SHES groups had daily isometric contraction training by electrostimulation(100Hz, 45mA, 7.5V) on hindlimb muscles for 7days. RESULT: Plantaris and gastrocenmius muscle weight, myofibrillar protein contents of soleus and gastrocnemius, and the muscle fiber cross-sectional area of gastrocnemius in the ST group significantly decreased compared with the SH group. Soleus, plantaris, gastrocnemius muscle weight, myofibrillar protein contents of soleus and gastrocnemius, and the Type I muscle fiber cross-sectional area of soleus and the Type II muscle fiber cross-sectional area of gastrocnemius in the STES group significantly increased compared with the ST group. CONCLUSION: Hindlimb muscle atrophy occurs after acute stroke and isometric contraction training by electrostimulation during early stages of a stroke attenuates muscle atrophy of Type I and Type II muscles.
Animals ; Body Weight ; Brain Ischemia/*complications ; Disease Models, Animal ; Electric Stimulation ; Hindlimb ; *Isometric Contraction ; Male ; Muscle Proteins/analysis ; Muscle, Skeletal/metabolism/pathology/*physiopathology ; Muscular Atrophy/*etiology/pathology/physiopathology ; Myofibrils/chemistry ; Rats ; Rats, Sprague-Dawley ; Stroke/*complications