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PubMed1992

Effect of partial denervation on motor units in the ageing rat medial gastrocnemius.

The ageing neuromuscular system is thought to undergo a continual process of reorganization as motoneurones are lost and surviving motor nerves reinnervate neighbouring denervated muscle fibres. However, the extent to which collateral reinnervation is able to compensate for neural deficits in the ageing individual is unknown. The ability of the senescent motoneurone to increase the size of its peripheral field was therefore investigated following transection of the right L5 ventral root in male Sprague Dawley rats aged 775 +/- 50 days. This procedure resulted in an extensive partial denervation of the right medial gastrocnemius muscle. After a recovery period of between 28 and 31 days the isometric contractile properties of surviving motor units were compared to control motor units from both the contralateral muscle and a group of unoperated control animals aged 791 +/- 39 days. Motor unit force was found to be unchanged after partial denervation and the absence of any alteration in motor unit size was confirmed by histological analysis. However, the time course of the isometric twitch was significantly longer for both fast and slow motor unit types and the conduction velocity of motoneurones innervating fast units was decreased following partial denervation. These results demonstrate that senescent motor nerves are unable to substantially increase the size of their peripheral fields by extensive collateral reinnervation.

Aging↗
PubMed2001

Differential expression and regulation of the PKA signalling pathway in fast and slow skeletal muscle.

To identify intracellular signalling pathways that transduce muscle electrical activity, we have investigated the Protein Kinase A (PKA) pathway in fast and slow skeletal muscle. The slow soleus muscle (SOL) displayed approximately twice as much PKA catalytic activity and cAMP-binding compared to the fast Extensor Digitorum Longus (EDL) muscle. These results were confirmed by Western blot analysis using antibodies directed against the catalytic or regulatory subunits of PKA. PKA subunits were concentrated at the neuromuscular junction in innervated and denervated muscle fibers demonstrating that PKA is expressed post-synaptically. In addition, we also detected PKA subunits outside the junctional area, suggesting that PKA functions outside of the synaptic regions. Following denervation, levels of cyclic AMP, PKA C activity, R cAMP-binding and RI alpha protein levels increased significantly in the SOL, in contrast to the EDL where only elevated levels of RI alpha protein were observed. These observations demonstrate that PKA levels in skeletal muscle are subject to control at several levels and suggest that some of the differences may be in the pattern of electrical activity that motoneurons impose on the SOL and EDL.

Animals↗
PubMed2002

The effect of two episodes of denervation and reinnervation on skeletal muscle contractile function.

Sensory or motor "baby-sitting" has been proposed as a clinical strategy to preserve muscle integrity if motion-specific axons must regenerate over a long distance to reach denervated target muscles. Denervated muscles are innervated temporarily by using axons from nearby sensory or motor nerves. After motion specific motor axons have reached the target, the baby-sitter nerve is severed and motion-specific axons are directed to the target. Although this strategy minimizes denervation time, the requisite second episode of denervation and reinnervation might be deleterious to muscle contractile function. This study was designed to test the hypothesis that two sequential episodes of skeletal muscle denervation and reinnervation result in greater force and power deficits than a single peripheral nerve injury and repair. Adult Lewis rats underwent either transection and epineurial repair or sham exposure of the left peroneal nerve. After a 4-month recovery period, the contractile properties of the extensor digitorum longus muscle of the sham exposure group (control, n = 9) and one of the nerve division and repair groups (repair group 1, n = 9) were evaluated with measurements of the maximum tetanic isometric force, peak power, and maximal sustained power. A third group of rats underwent a second cycle of nerve division and repair (repair group 2, n = 9) at this same time point. Four months postoperatively, contractile properties of the extensor digitorum longus muscles were evaluated. Maximum tetanic isometric force and peak power were significantly reduced in repair group 2 rats as compared with repair group 1 and control rats. Maximal sustained power was not significantly different between the groups. These data support our working hypothesis that skeletal muscle contractile function is adversely affected by two cycles of denervation and reinnervation as compared with a single episode of nerve division and repair.

Animals↗
PubMed1987

Postnatal loss of synaptic terminals in the partially denervated mouse soleus muscle.

The present work aims to distinguish between processes that lead to neonatal synapse elimination. We have partially denervated the mouse soleus muscle just after birth by cutting one (L5) of the two (L4 and L5) spinal nerves which supply its innervation. After 4-6 weeks' survival times, we determined the number of remaining motor units (MUs) and the number of innervated fibres in the muscle by conventional physiological and histological techniques. There was no significant overlap between the remaining MUs. Their average size was reduced from about 230 muscle fibres at birth to about 80 after 4-6 weeks, compared to only 30 in normal animals of the same age. We conclude that two processes are required to explain synapse elimination in the muscle: a non-competitive process, inherent to the immature motor neurons and leading to a substantial reduction in their field of innervation; a competitive process between axon terminals innervating the same muscle fibre.

Action Potentials↗
PubMed1994

The influence of sympathoadrenal activation on skeletal muscle oxygen extraction during endotoxemia.

We have previously shown a direct relationship (r = .97) between the fall in arterial blood pressure and the increase in skeletal muscle oxygen extraction (MVO2) during canine endotoxemia. Since it is well known that hypotension activates the sympathetic system, the primary aim of these experiments was to determine if the increase in MVO2 during endotoxemia is a result of elevated levels of catecholamines due to increased sympathetic neural and/or humoral activity (sympathoadrenal system). Canine gracilis muscles were vascularly isolated and perfused in situ at a constant flow (6-7 ml/min/100 g). Endotoxemia was induced by a 30 min intravenous infusion of Escherichia coli endotoxin (2 mg/kg), which induced a 50% reduction in arterial pressure. Perfusion pressure, mean arterial pressure, and arteriovenous oxygen difference (a-v O2) were continuously measured. We found 1) no significant difference between the amount of O2 extracted by an innervated or a denervated muscle during endotoxemia; 2) the intra-arterial infusion of norepinephrine or epinephrine into a denervated gracilis muscle (plasma molar concentrations of; 10(-11), 10(-9), 10(-7), and 10(-5) failed to increase MVO2 to the level observed during endotoxemia; 3) pretreatment of a muscle with propranolol to block skeletal muscle beta-adrenergic receptors, did not suppress the endotoxin-induced rise in MVO2. We concluded that the increase in MVO2 seen after the administration of endotoxin is not due to either increased sympathetic nerve activity or elevated levels of circulating catecholamines. We speculate that the increased MVO2 during endotoxemia is caused by nonadrenergic mediators released by endotoxin rather than the hypotensive stimulus.

Adrenal Cortex↗
PubMed1986

Overwork effect on partially denervated rat soleus muscle.

The purpose of this study was to assess the effect of overwork induced by synergistic tenotomy on the muscle weight (MW) and isometric tetanic tension (Po) of the partially denervated rat soleus muscle. Forty-nine young adult male Sprague-Dawley rats were divided into six groups (n = 5 to 9): normal control (N), normal synergistically tenotomized (N-ST), L4 denervated control (L4), L4 denervated synergistically tenotomized (L4-ST), L5 denervated control (L5), and L5 denervated synergistically tenotomized (L5-ST). Bilateral L4 or L5 root transections produced partial denervation. To yield soleus muscle overwork the gastrocnemius and plantaris muscles were bilaterally tenotomized in all ST groups at the time of denervation. The soleus MW and Po were examined seven days following denervation and tenotomy. Compared to their respective controls, there was increased MW in the N-ST (43.5%, p less than 0.01) and the L4-ST (38.6% p less than 0.01) groups. The L5-ST group showed no significant change in MW compared to the L5 group. Tetanic tension was increased only in the N-ST group. The L4-ST and L5-ST groups did not show any change in Po compared to their respective controls. Despite marked denervation, the L5 group did not show any atrophy as compared to the N group, suggesting passive stretch of the denervated muscle fibers, hypertrophy of the innervated muscle fibers and peripheral sprouting prevented the loss of MW due to denervation. Overwork in this markedly denervated group could not produce any increase in the MW or Po.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

Extracellular recording of localized electrical activity in denervated frog slow muscle fibres.

Pyriformis muscles of Rana temporaria were denervated by cutting the sciatic nerve in the pelvis. Slow muscle fibres were depolarized with intracellular current pulses, and the electrical activity was recorded simultaneously with intracellular and extracellular recording electrodes. When the extracellular electrode was moved along the fibre surface, outward and inward currents of variable amplitude were recorded. Inward currents coincided with the fast rising phase of the intracellularly recorded action potential; up to four inward current peaks could be detected in single fibres investigated over 3.4--8 mm of their length. The distance between inward current peaks was generally 1--2 mm, but greater distances were also observed. Composite action potentials could be shown to be due to inward currents arising in separate areas of the slow fibre membrane. It is concluded that after denervation Na-channels are incorporated into spatially limited areas of the membrane of slow muscle fibres.

Action Potentials↗
PubMed1976

Spontaneous activity in denervated mouse diaphragm muscle.

Intracellular electrodes were used to study the discrete depolarizations which trigger fibrillation potentials in chronically denervated mouse diaphragm muscles. Provided that the muscles were perfused on both sides spontaneous activity was maintained in vitro. 2. Discrete spontaneous depolarizations, present only in the centre of the muscle, were recorded from the third day of denervation reaching a maximum in prevalence 9-12 days after sectioning the nerve. These potentials had random occurrence and nearly constant amplitude and frequency within a fibre, dependence of amplitude and frequency on membrane potential, and low temperature dependence. 3. The spontaneous activity was enhanced and could be initiated in previously quiescent fibres by lowering the external Ca concentration. The activity was reduced by increasing external Ca and was abolished at 15mM-[Ca] 0. Tetrodotoxin (10-(7)M) blocked spontaneous activity. 4. The spontaneous activity was enhanced by the catecholamines isoprenaline and adrenaline (0.5-10 mug/ml.). This effect of isoprenaline was accompanied by an increase in the rate of rise and the amount of overshoot of the action potential. 5. Ouabain (10-(6)-10-(4)M) of K+-free solutions reversibly blocked spontaneous activity. Ouabain (10-(4)M) reduced the rate of rise and the amount of overshoot of the action potential. 6. Detubulation of muscle fibres with glycerol of the presence of hypertonic solutions abolished spontaneous activity which could not be restarted by reducing Ca or by the addition of isoprenaline. 7. The results support the suggestion that the spontaneous discrete depolarizations which give rise to fibrillation potentials in denervated muscle result from regenerative sodium conductance increases within the transverse tubular system of the muscle fibres. Catecholamines and ouabain could affect this activity either directly, through an action on membrane excitability, or indirectly via the Na+-K+ pump.

Action Potentials↗
PubMed1999

The age dependent effect of partial denervation of rat fast muscles on their activity.

In 3 or 18 day old Wistar rats the hindlimb muscles were partially denervated by cutting the L4 spinal nerve. Three months later, the effects of partial denervation of the fast extensor digitorum longus (EDL) muscle on the activity of its remaining motor units were studied using electromyographic (EMG) recordings in freely moving animals. In spite of a reduced number of motor units the amount of aggregate EMG activity was greater in the partially denervated EDL muscle in all experimental conditions. This increase was more obvious at rest than during exploratory behaviour, and was significantly greater in muscles that were partially denervated at 3 days than at 18 days of age. On the other hand, the effect of partial denervation on the EMG activity pattern during locomotion was similar in animals partially denervated at 3 or 18 days of age. Unlike in intact EDL, in the partially denervated EDL muscle the duration of the bursts was influenced by the step cycle duration. Thus, we conclude that although partial denervation of EDL muscle influences the amount and pattern of activity of the remaining undamaged motor units in all animals, some of the alterations of EMG activity were more pronounced in animals denervated at younger age.

Aging↗
PubMedDate not supplied

Muscle reorganization after partial denervation and reinnervation.

The normal rat tibialis anterior (TA) muscle was found to be innervated by approximately 154 spinal motor cells of which 95 are alpha motoneurons. Most of these axons ran in the L4 root and connected with glycolytic type 2B muscle fibers. The L5 root supplied 8.4% to 14.7% of the motor axons of TA muscle and innervated type 1 and 2A muscle fibers rich in oxidative enzymes. Two months after section of the peroneal nerve, there was marked fiber-type grouping and compact rearrangement of the L4 and L5 motor units. After section of the L4 radicular nerve, the TA muscle remained atrophic with no evidence of fiber-type grouping until 3 months when the L4 regenerating axons reached the muscle. Similar results were obtained after ligation of the divided ends of the L4 radicular nerve, which delayed but did not prevent reinnervation. These data suggest that, after partial denervation, muscle reinnervation by collateral sprouting is a slowly developing process.

Animals↗
PubMed1983

A quantitative ultrastructural analysis of satellite cells in denervated fast and slow muscles of the mouse.

Mononucleated cells located between the external lamina and sarcolemma of denervated muscle fibers within the extensor digitorum longus (EDL) and soleus muscles of adult mice were quantified and examined ultrastructurally from 3 to 65 days after ligating and removing a section of the sciatic nerve. During the first 2 weeks postdenervation, mononucleated cells in denervated muscles were morphologically indistinguishable from satellite cells observed in control muscles. With time, however, many of these satellite-like cells appeared more active as evidenced by a decrease in their nucleocytoplasmic ratio and an increase in their mean percentage of euchromatin material. The number of satellite cells (expressed as a ratio of satellite cell nuclei to satellite cell nuclei plus myonuclei) did not increase significantly until 30 days postdenervation, at which time the mean percentage for the soleus muscle had risen from a control value of 4.1-8.5%, and for the EDL from 1.2-4.1%. Small-diameter, presumably regenerating, myofibers were occasionally observed but only after 30 days denervation. The ultrastructural evidence plus comparisons of euchromatin distributions between myonuclei and satellite cell nuclei support the concept that an increase in the number of satellite-like cells during denervation is more likely due to satellite cell proliferation than to the formation of mononucleated fragments utilizing preexisting myonuclei.

Animals↗
PubMed1979

Nerve sheaths and motoneurone collateral sprouting.

When disease or injury causes partial loss of innervation from a muscle, the remaining axons sprout and form new connections to the denervated muscle fibres. Sprouting can occur in two ways: from axon terminals (terminal sprouting) or from the intramuscular axons themselves, probably from the nodes of Ranvier (collateral sprouting). Terminal sprouting has been induced experimentally using various methods, including partial denervation, nerve conduction block and nerve transmission block. A common factor in the induction of terminal sprouting seems to be changes in the surface membrane of muscle fibres; these changes and terminal sprouting are prevented by direct stimulation of the muscle. Collateral sprouting has been induced only by partial denervation and is not prevented by direct stimulation. This has been taken as evidence for an earlier suggestion that products of nerve or axon degeneration may be a direct stimulus for collateral sprouting. We report here that axon degeneration products alone are probably not the stimulus for collateral sprouting.

Acetylcholinesterase↗
PubMed1998

The non-synaptic expression of transforming growth factor-beta 2 is neurally regulated and varies between skeletal muscle fibre types.

In adult skeletal muscles, transforming growth factor-beta 2 is restricted to the postsynaptic domain of the neuromuscular junction. The various putative functions of this transforming growth factor-beta 2 predict different patterns of transforming growth factor-beta 2 expression in denervated muscles. We therefore denervated rat tibialis anterior, extensor digitorum longus and soleus muscles and examined the expression of transforming growth factor-beta 2 using semi-quantitative reverse-transcription polymerase chain reaction and immunohistochemistry. Denervation up-regulated transforming growth factor-beta 2 expression extrasynaptically with little or no effect on synaptic expression. The up-regulation was detectable by one day, had become significant by three days and remained elevated for at least two weeks. This proves that the transforming growth factor-beta 2 associated with the neuromuscular junction is not under neural control and is consistent with transforming growth factor-beta 2 being a trophic factor for motoneurons. This pattern of transforming growth factor-beta 2 expression is similar to that described for other proteins associated with the neuromuscular junction, notably the acetylcholine receptor subunit genes. However, in contrast to the acetylcholine receptor subunit genes, the extent of up-regulation of transforming growth factor-beta 2 varied between fibre types, with the glycolytic IIB fibres being less affected than other fibre types.

Animals↗
PubMedDate not supplied

Neurogenic atrophy of suboccipital muscles after a cervical injury: a case study.

This case report describes abnormalities in bilateral rectus capitis posterior minor muscles in one individual with persistent head and neck pain. These findings are muscle atrophy, fatty infiltration on magnetic resonance imaging, and electromyographic abnormalities compatible with denervated muscle. The objective of the study contained herein was to determine if fatty infiltration on magnetic resonance imaging of the rectus capitis posterior minor muscle is the result of disuse or denervation. Electromyography and magnetic resonance imaging data were collected from normal and atrophied muscles. Electromyography and magnetic resonance imaging abnormalities compatible with denervation atrophy were detected. Although we cannot rule out aging or other unknown causes, we suspect that denervation is caused by nerve damage from trauma to the C1 dorsal ramus as a consequence of entrapment within the rectus capitis posterior major muscle.

Adipose Tissue↗
PubMed1976

The membrane potential of rat diaphragm muscle fibres and the effect of denervation.

1. Resting membrane potentials of rat diaphragm muscles were measured in vitro after previous denervation for 0-10 days. In some experiments denervated muscles were incubated in vitro for 3 hr while in others they were cultured for 15-24 hr to allow adequate exposure to drugs before recording. 2. It was found that resting membrane potentials, within 2-5 mm of the site of nerve section were significantly lower, within 3 hr, than resting membrane potentials measured more than 9 mm away from site of nerve section. This difference could be reduced or abolished by bathing preparations in solutions containing adrenaline (10 muM), noradrenaline (10 muM) or isoprenaline (10 muM) or dibutyryl cyclic AMP (10 muM-0-25 mM in the presence of 2 mM theophylline). Cyclic AMP (0-5 mM) was ineffective. 3. Application of solutions containing dibutyryl cyclic AMP for 3 hr also raised the resting membrane potential of muscles denervated 4-5 days previously. Culture studies showed that this effect was sustained when the time of incubation was 24 hr. 4. Incubating freshly denervated preparations with cycloheximide (22 mug/ml.) or actinomycin D (1 mug/ml.) did not prevent the development of the early (3 hr) fall in resting membrane potential despite a concomitant inhibition of RNA or protein synthesis. Culturing freshly denervated muscles in solutions containing cycloheximide (10 or 25 mug/ml.) which blocked 93% of protein synthesis, did not prevent the expected drop in resting membrane potential after 15 or 24 hr. 5. It was found that exposure to ouabain (1 or 5 mM) produced a rapid (15 min) fall in resting membrane potential in innervated and denervated preparations treated with dibutyryl cyclic AMP but not denervated preparations. After 5 days denervation cyclic AMP levels in muscle were increased by about 40%. 6. It is suggested that upon denervation an electrogenic action of a NA+-pump is blocked and that dibutyryl cyclic AMP and catecholamines are capable of stimulating this pump.

Animals↗
PubMed2005

Denervation enhances the expression of SHPS-1 in rat skeletal muscle.

SHPS-1 (Src homology 2 domain containing protein tyrosine phosphatase substrate 1) is a transmembrane glycoprotein containing three immunoglobulin-like motifs in its extracellular domain and immunoreceptor tyrosine-based inhibitory motifs (ITIM) that interact with SHP-2 (Src homology 2 domain containing protein tyrosine phosphatase-2) in its cytoplasmic region. SHPS-1 is highly expressed in brain, but at much lower levels in skeletal muscle. In this study, we found that the level of the SHPS-1 mRNA increases in rat skeletal muscle after denervation. Western blot analysis also confirmed the increase of SHPS-1 in denervated muscle. Moreover, it was found that the glycosylation of SHPS-1 is N-linked in a muscle-specific manner, and that this is altered upon innervation or denervation. Immunohistochemistry revealed SHPS-1 immunoreactivity at neuromuscular junctions (NMJs) under innervation, whereas immunoreactivity was observed extrasynaptically in muscle fibers after denervation. Our results indicate that the expression, glycosylation, and localization of SHPS-1 are strongly regulated by the nervous system, and that SHPS-1 may play an important role in denervated skeletal muscle.

Animals↗