Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration.
(65/1234)
To test the hypothesis that inhibition of axonal transport is sufficient to cause motor neuron degeneration such as that observed in amyotrophic lateral sclerosis (ALS), we engineered a targeted disruption of the dynein-dynactin complex in postnatal motor neurons of transgenic mice. Dynamitin overexpression was found to disassemble dynactin, a required activator of cytoplasmic dynein, resulting in an inhibition of retrograde axonal transport. Mice overexpressing dynamitin demonstrate a late-onset progressive motor neuron degenerative disease characterized by decreased strength and endurance, motor neuron degeneration and loss, and denervation of muscle. Previous transgenic mouse models of ALS have shown abnormalities in microtubule-based axonal transport. In this report, we describe a mouse model that confirms the critical role of disrupted axonal transport in the pathogenesis of motor neuron degenerative disease. (+info)
Scapuloperoneal atrophy with sensory involvement: Davidenkow's syndrome.
(66/1234)
A patient with scapuloperoneal atrophy of neurogenic type, in whome there was also distal sensory impairment, has been studied with conventional EMG, single fibre EMG, and muscle biopsy. This disorder, described by Davidenkow, may be a distinct entity. (+info)
Muscle-related traits in cattle: The role of the myostatin gene in the South Devon breed.
(67/1234)
In this paper, we examined the effects of an 11-bp mutation within the GDF-8 gene, originally identified in Belgian Blue cattle, in the South Devon breed. The mutation was found at moderate frequency (0.37) in the South Devon population. We quantified the effects of this mutation on growth, body composition and calving traits in South Devon cattle. We found that the mutation significantly increased muscle score and calving difficulty and decreased fat depth. The mutation did not significantly affect weight at 200 and 400 days or muscle depth. Its effect on muscle score and fat depth was additive while its effect on calving difficulty was recessive. The mutation accounted for a significant proportion of the phenotypic variance in muscle score and calving difficulty. There was an economic benefit of the mutation for this data set, however, calculations were sensitive to changes in the parameter values. Additional data would be required to refine these calculations. (+info)
Muscle fiber type IIX atrophy is involved in the loss of fat-free mass in chronic obstructive pulmonary disease.
(68/1234)
BACKGROUND: Although the loss of peripheral muscle mass has been shown convincingly in chronic obstructive pulmonary disease (COPD), the underlying pathogenesis remains unclear. OBJECTIVE: The aim of the present study was to determine the relations between skeletal muscle fiber types, fiber cross-sectional area (CSA), enzyme activities, and fat-free mass (FFM) in patients with COPD and in control subjects. DESIGN: In 15 patients with COPD and 15 healthy, age-matched control subjects, FFM was determined by dual-energy X-ray absorptiometry and bioelectrical impedance analysis. In biopsy specimens from the vastus lateralis fiber types, fiber CSA and activities of cytochrome oxidase (EC 1.9.3.1), succinate dehydrogenase (EC 1.3.99.1), and glycogen phosphorylase (EC 2.4.1.1) were examined immunohistochemically and histochemically. RESULTS: Compared with control subjects, patients with COPD had less FFM (49 compared with 59 kg, P = 0.030) and lower mean fiber CSA (3839 compared with 4647 microm(2), P = 0.037). A strong correlation (r = 0.87, P < 0.001) was observed between the FFM measured by bioelectrical impedance analysis and mean fiber CSA in patients with COPD. Within fiber-type categories the mean CSA of only the IIA/IIX and IIX fiber types was lower in patients than in control subjects [3358 compared with 4428 microm(2) (P = 0.022) and 2566 compared with 4248 microm(2) (P = 0.003), respectively]. In COPD, 20% of the type IIX fibers lacked stainable activities of cytochrome oxidase, succinate dehydrogenase, and glycogen phosphorylase, and this proportion correlated negatively with type IIX fiber CSA (r = -0.65, P = 0.012). CONCLUSIONS: Muscle fiber atrophy occurs in the vastus lateralis in patients with COPD and contributes to the loss of muscle mass in COPD. Atrophy is specific to fiber types IIA/IIX and IIX and is associated with a disturbed metabolic capacity. (+info)
A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification.
(69/1234)
Nerve activity controls fiber size and fiber type in skeletal muscle, but the underlying molecular mechanisms remain largely unknown. We have previously shown that Ras-mitogen-activated protein kinase and calcineurin control fiber type but not fiber size in regenerating rat skeletal muscle. Here we report that constitutively active protein kinase B (PKB), also known as Akt, increases fiber size and prevents denervation atrophy in regenerating and adult rat muscles but does not affect fiber type profile. The coexistence of hypertrophic muscle fibers overexpressing activated PKB with normal-size untransfected fibers within the same muscle points to a cell-autonomous control of muscle growth by PKB. The physiological role of this pathway is confirmed by the finding that PKB kinase activity and phosphorylation status are significantly increased in innervated compared with denervated regenerating muscles in parallel with muscle growth. Muscle fiber hypertrophy induced by activated PKB and by a Ras double mutant (RasV12C40) that activates selectively the phosphoinositide 3-kinase-PKB pathway is completely blocked by rapamycin, showing that the mammalian target of rapamycin kinase is the major downstream effector of this pathway in the control of muscle fiber size. On the other hand, nerve activity-dependent growth of regenerating muscle is only partially inhibited by dominant negative PKB and rapamycin, suggesting that other nerve-dependent signaling pathways are involved in muscle growth. The present results support the notion that fiber size and fiber type are regulated by nerve activity through different mechanisms. (+info)
Dystrophin-glycoprotein complex and Ras and Rho GTPase signaling are altered in muscle atrophy.
(70/1234)
The dystrophin-glycoprotein complex (DGC) is a sarcolemmal complex whose defects cause muscular dystrophies. The normal function of this complex is not clear. We have proposed that this is a signal transduction complex, signaling normal interactions with matrix laminin, and that the response is normal growth and homeostasis. If so, the complex and its signaling should be altered in other physiological states such as atrophy. The amount of some of the DGC proteins, including dystrophin, beta-dystroglycan, and alpha-sarcoglycan, is reduced significantly in rat skeletal muscle atrophy induced by tenotomy. Furthermore, H-Ras, RhoA, and Cdc42 decrease in expression levels and activities in muscle atrophy. When the small GTPases were assayed after laminin or beta-dystroglycan depletion, H-Ras, Rac1, and Cdc42 activities were reduced, suggesting a physical linkage between the DGC and the GTPases. Dominant-negative Cdc42, introduced with a retroviral vector, resulted in fibers that appeared atrophic. These data support a putative role for the DGC in transduction of mechanical signals in muscle. (+info)
Pathophysiology and treatment for cervical flexion myelopathy.
(71/1234)
Previous studies have suggested that spinal cord compression by the vertebral bodies and intervertebral discs during neck flexion cause cervical flexion myelopathy (CFM). However, the exact pathophysiology of CFM is still unknown, and surgical treatment for CFM remains controversial. We examined retrospectively patients with CFM based on studies of the clinical features, neuroradiological findings, and neurophysiological assessments. The objectives of this paper are to investigate the pathophysiology of CFM, and to examine an optimal surgical treatment. Twenty-three patients (20 male, three female) with age of onset ranging from 11 to 23 years (mean 15.7 years) were examined for the study. All patients were inspected by magnetic resonance imaging (MRI), myelogram, or computed tomographic myelogram (CTM) of the cervical spine. In eight patients, dynamic motor evoked potentials (MEP) studies were performed. Five patients underwent surgical treatment; two patients had cervical duraplasty with laminoplasty, two patients had musculotendinous transfer, one patient had both of these procedures, and the remaining 18 patients were treated conservatively. Amyotrophy of the hand intrinsic and flexor muscle group of the forearm except the brachioradial muscle was observed hemilaterally in 20 patients and bilaterally in three patients. In three patients, T1-weighted MRI with neck flexion showed linear high intensity regions in the epidural space. In all patients, axial MRI/CTM demonstrated flattening of the spinal cord with the posterior surface of the dura mater shifting anteriorly. The amplitude of MEPs decreased after cervical flexion in two patients with progressive muscular atrophy. In three patients, dysesthesia of the upper extremities disappeared following cervical duraplasty. Musculotendinous transfer for three patients significantly improved the performance of their upper extremity. The findings of this study suggest that degenerative changes of the dura mater may be a characteristic pathology of CFM. Cervical duraplasty with laminoplasty is effective for cases at an early stage, and musculotendinous transfer should be selected in patients at a late stage. (+info)
Cervical myelopathy due to a "tight dural canal in flexion" with a posterior epidural cavity.
(72/1234)
A 41-year-old man noticed weakness and atrophy in his right hand and forearm resembling the non-progressive juvenile muscular atrophy of unilateral upper extremity (Hirayama's disease). MRI showed an abnormal cavity in the posterior epidural space which appeared on neck flexion communicating with the subarachnoid space in addition to the flattening of the lower cervical spinal cord on neck flexion. When evaluating atypical cases of Hirayama's disease, the pathomechanism demonstrated in the present case should be taken into consideration. (+info)