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PubMed1995

Myenteric denervation of rat jejunum alters calcium responsiveness of intestinal smooth muscle.

BACKGROUND/AIMS: Long-term myenteric and extrinsic denervation of a segment of rat jejunum results in increased stress generation by the longitudinal muscle layer of the denervated segment 15 days after denervation. This study examined whether alterations in the properties of either cell membrane calcium channels and/or sarcoplasmic reticular Ca(2+)-adenosine triphosphatase (ATPase) contribute to the increased stress development. METHODS: The effects of the calcium channel blocker nifedipine and the sarcoplasmic reticular Ca(2+)-ATPase inhibitor cyclopiazonic acid on the contractile activity of denervated and control smooth muscle were determined. RESULTS: The ability of nifedipine to inhibit KCl-induced contractions was significantly increased in denervated tissues; however, there was no difference in the potency of nifedipine when tissues were stimulated with carbachol. Calcium concentration-response curves obtained in the presence of either KCl or carbachol were determined in tissues previously depleted of calcium. Long-term denervated tissues showed an increased sensitivity to calcium and a decreased maximum contractile response after stimulation with carbachol. Cyclopiazonic acid inhibited repletion of intracellular calcium stores of control muscle but had no effect in denervated tissue. CONCLUSIONS: Long-term denervation of a segment of rat small intestine results in profound alterations in calcium metabolism at the cell membrane and, to a lesser extent, at the sarcoplasmic reticulum of smooth muscle cells of the longitudinal muscle layer.

Animals↗
PubMed1990

Different mechanisms of increased proteolysis in atrophy induced by denervation or unweighting of rat soleus muscle.

Mechanisms of accelerated proteolysis were compared in denervated and unweighted (by tail-cast suspension) soleus muscles. In vitro and in vivo proteolysis were more rapid and lysosomal latency was lower in denervated than in unweighted muscle. In vitro, lysosomotropic agents (eg, chloroquine, methylamine) did not lessen the increase in proteolysis caused by unweighting, but abolished the difference in proteolysis between denervated and unweighted muscle. Leucine methylester, an indicator of lysosome fragility, lowered latency more in denervated than in unweighted muscle. 3-Methyladenine, which inhibits phagosome formation, increased latency similarly in all muscles tested. Mersalyl, a thiol protease inhibitor, and 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8), which antagonizes sarcoplasmic reticulum release of Ca2+, reduced accelerated proteolysis caused by unweighting without diminishing the faster proteolysis due to denervation. Calcium ionophore (A23187) increased proteolysis more so in unweighted than control muscles whether or not Ca2+ was present. Different mechanisms of accelerated proteolysis were studied further by treating muscles in vivo for 24 hours with chloroquine or mersalyl. Chloroquine diminished atrophy of the denervated but not the unweighted muscle, whereas mersalyl prevented atrophy of the unweighted but not of the denervated muscle, both by inhibiting in vivo proteolysis. These results suggest that (1) atrophy of denervated, but not of unweighted, soleus muscle involves increased lysosomal proteolysis, possibly caused by greater permeability of the lysosome, and (2) cytosolic proteolysis is important in unweighting atrophy, involving some role of Ca2(+)-dependent proteolysis and/or thiol proteases.

Animals↗
PubMed1984

Acute sinoaortic denervation induces pre- and postsynaptic alpha-adrenergic subsensitivity in mesenteric arteries in the rat.

Bilateral sinoaortic denervation induced a rapid increase in blood pressure and heart rate in the rat. Four hours after sinoaortic denervation, the dose-response curve to l-norepinephrine (NE) in perfused mesenteric arteries in vitro was shifted to the right and the maximal response reduced, compared with sham-operated controls. These changes were abolished in the presence of cocaine (10 micrograms/ml). Four hours after sinoaortic denervation, the dose-response curves to methoxamine and serotonin, but not to adenosine-5'-triphosphate (ATP), were significantly reduced and the muscular response induced by barium chloride was not modified. Vascular responses to stimulation with different frequencies of the sympathetic nerve were reduced 4 hr after sinoaortic denervation. These changes in both the responses to l-NE and to nerve stimulation were reversed 24 hr after sinoaortic denervation. In the same preparation, 4 hr after sinoaortic denervation, the fractional release per pulse of [3H]-NE was significantly enhanced at 10 and 20 Hz frequencies of stimulation, whereas the blockade of the alpha-presynaptic receptors with phentolamine (3.1 microM) did not increase the release of [3H]-NE induced by nerve stimulation, as was observed in sham-operated controls. The results are compatible with the hypothesis that 4 hr after sinoaortic denervation, the pre- and postsynaptic alpha-adrenoceptors are desensitized. These changes could affect arterial sympathetic neurotransmission; the increase in blood pressure observed following sinoaortic denervation could therefore not be explained only by an increase in sympathetic tone.

Animals↗
PubMed1993

Role of vasoconstrictor tone in arterial pressure lability after chronic sympathectomy and sinoaortic denervation in rats.

In both chronically sympathectomized (SNX) and sinoaortic denervated (SAD) rats, removal of vasoconstrictor influences decreases mean arterial pressure (MAP) and its variability in parallel. This study examined if this decrease in arterial pressure lability is solely a result of decreasing vascular tone. In conscious 14-week-old male sympathectomized (guanethidine at 1-13 weeks of age) and sinoaortic denervated (2 weeks before study) rats, arterial pressure was recorded beat-to-beat during 30-min consecutive periods; control; ganglionic blockade in sinoaortic denervated rats and angiotensin converting enzyme inhibition plus vasopressin antagonism in sympathectomized rats; and restoration of the initial arterial pressure with continuous infusions of phenylephrine and angiotensin II. Sympathectomized and, even more, sinoaortic denervated rats had increased pressure variability. Neural or humoral blockade markedly reduced arterial pressure and its liability in both groups of rats and subsequent restoration of the arterial pressure with vasoconstrictor infusions returned lability to levels either slightly above (sympathectomy) or below (sinoaortic denervation) control values. In basal conditions, an increased frequency of occurrence of depressor episodes was evidenced in sympathectomized rats whereas a variable ratio of pressor to depressor events was observed in sinoaortic denervated rats. During vasoconstrictor infusions, blood pressure lability was mainly due to depressor events in both groups of rats. It is concluded that the background vascular tone provided by endogenous pressor systems is necessary for the expression of the depressor component of blood pressure lability in sinoaortic denervated and in sympathectomized rats. The study also suggests that in sympathectomized rats, humoral influences act to limit rather than enhance blood pressure lability, whereas in sinoaortic denervated rats, the sympathetic nervous system may directly generate part of the lability.

Angiotensin II↗
PubMed1985

Autotomy following limb denervation: effects of previous exposure to neurectomy.

Neurectomy, dorsal rhizotomy or spinal cord lesions can evoke self-attack and autotomy of portions of insensate limbs. This behavior has been attributed to dysesthesia and/or pain. However, the majority of animals subjected to these lesions do not exhibit self-mutilation. This study was designed to test for individual predisposition to self-mutilative behaviors by effecting two sequential limb denervations. In susceptible animals, denervation of the first limb induced circulatory, trophic and inflammatory reactions and/or autotomy. Inflammation developed slowly in one or two digits of some animals and then spontaneously resolved. Other animals attacked the tips of inflamed digits effecting local autotomy. Still other animals aggressively attacked multiple digits, rapidly developed diffuse inflammation and produced extensive autotomy. Denervation of a second limb, following complete healing of all tissue injury, induced by the first denervation, produced several dramatic responses. Nearly 90% of those responding with autotomy to the first denervation responded with autotomy to the second denervation. In contrast, only 11% of the non-attackers showed autotomy following the second denervation. The inflammatory and autotomy responses to the second denervation were markedly reduced in latency and increased in intensity. The pattern of autotomy was stereotyped, initiated at the digit tips, progressed proximally, lead by advancing inflammation. It is suggested that a strong host-response component is involved in the autotomy response.

Afferent Pathways↗
PubMed1984

A quantitative study of the time course of the reduction in Merkel cell number within denervated rat touch domes.

By using the fluorescent dye quinacrine as a marker for the Merkel cells in rat touch domes we have shown that denervation results in a progressive reduction in the number of these cells to a level that remains relatively constant at about 40% of that present at the time of denervation. The time-course of quinacrine fluorescent cell changes after denervation could be described by assuming that (i) there are two populations of quinacrine fluorescent cells, one labile and the other stable, and (ii) the labile population is the one most sensitive to denervation and disappears exponentially with a half-time of ca 10 days. It appeared that this time-course of decay of the labile quinacrine fluorescent cells was the same whether the denervation was performed during the period of postnatal development studied (at 7 and 14 days), when normally Merkel cells are rapidly added to the dome, or later (at 35 and 60 days) when the adult population is virtually established. Correlative electron microscopic studies confirmed that quinacrine fluorescent cell counts reflect fairly accurately the Merkel cell population in denervated domes. These quantitative findings based on the use of quinacrine to visualize the entire Merkel cell population of touch domes show that the normal development and maintenance of these cells are trophically dependent on sensory nerves, although a subpopulation may persist even in long-term denervated domes. In addition, the similarity of the first order rate constant for the decay of quinacrine fluorescent cells after denervation and for the normal generation of quinacrine fluorescent cells suggests that the labile Merkel cell population is one that turns over continuously in the normally innervated touch dome.

Aging↗
PubMed1988

Localization of neural cell adhesion molecule in denervated muscle to both the plasma membrane and extracellular compartments by immuno-electron microscopy.

The location of neural cell adhesion molecule in mouse skeletal muscle has been investigated using two immuno-electron microscopical techniques. In the first method, 6-micron frozen sections of a normal and a hemi-denervated gluteus muscle were stained by an indirect immunoperoxidase method using a rabbit-derived polyclonal antiserum to neural adhesion molecule as the primary antibody. The stain was visualized with the electron-dense chromogen, diaminobenzidine and the sections fixed, osmicated and processed for electron microscopy whilst still on the slide. Ultrathin sections were cut and viewed in the electron microscope, where the reaction product appeared to be localized in the plasma membrane and on the basal lamina of the muscle fibres. The second method, using a 5-nm immunogold-labelled secondary antibody, confirmed and extended these initial observations. In these experiments, the primary antibody to neural cell adhesion molecule was applied in vivo to hemi-denervated mouse gluteus muscles. The muscles were dissected out 24 h later, divided into denervated and innervated halves and then into junctional and extrajunctional regions. Together with the junctional and extrajunctional regions of normal, control pieces of muscle which had not been incubated with anti-neural cell adhesion molecule, they were lightly fixed, and incubated with the secondary gold-labelled antibody, before further fixation and processing for electron microscopy. Semi-thin, 0.5-micron sections of each were cut and viewed at 20,000 x magnification. Randomly sampled fibres from the extrajunctional regions of the denervated and innervated halves of the hemi-denervated gluteus and the normal, control gluteus were photographed for quantitative analysis. Five micrographs were randomly selected from each group and in these, the numbers, density and position of gold particles were measured using a digitizing tablet. By far the highest number of gold particles was found in the denervated half of the gluteus muscle, there being much less in the innervated half and practically none in the control. The density of gold particles in the denervated muscles was maximal in the plasma membrane-basal lamina complex, but most were located in the extracellular spaces outside this region, where they usually occurred in clusters apparently in association with collagen fibres. We conclude that neural cell adhesion molecule in denervated skeletal muscle is present not only in the plasma membrane but also in the basal lamina and extracellular space.

Animals↗
PubMed1989

The onset of myogenesis in denervated mouse skeletal muscle regenerating after injury.

Denervation of skeletal muscle stimulates increased turnover of muscle nuclei and connective tissue cells. The present investigation tests whether denervation "primes" myogenic precursor cells, so that the onset of DNA synthesis in muscle precursors after traumatic injury occurs earlier than in innervated muscle. The left legs of 29 male BALBc mice were denervated, and 1 week later small incisions were made in the tibialis anterior muscles of both legs (denervated and innervated). At specific times after injury each mouse was injected once with tritiated thymidine to label replicating muscle precursors. Muscle lesions were sampled 10 days after injury (when all precursors had fused to form myotubes) and prepared for auto-radiography. The presence of labelled myotube nuclei showed that muscle precursors had been synthesizing DNA at the time when [3H]thymidine had been injected. Our data suggest that very few precursors were proliferating in denervated muscle within 30 h after injury, and the onset of myogenesis at 30 h was essentially the same in denervated and innervated muscle. The retrospective analysis indicates that there were also similar proportions of muscle precursors proliferating at different times after injury, in regenerating lesions of both denervated and innervated muscle. Thus, denervation does not stimulate an earlier regenerative response in injured skeletal muscle.

Animals↗
PubMed1990

Ultraterminal sprouting in innervated and partially denervated adult and aged rat muscle.

End plates from the extensor digitorum longus, soleus and diaphragm muscles of adult (10-month-old) and aged (25-month-old) rats were examined to determine whether aging affects the frequency of occurrence of ultraterminal sprouting, a form of terminal sprouting commonly associated with muscle denervation. There was a significant increase in the fraction of end plates exhibiting ultraterminal sprouts in the extensor digitorum longus muscle only; the number increased from 5.5% in 10-month-old animals to 23.0% in 25-month-old animals. To see whether age also influences the sprouting response to denervation, extensor digitorum longus muscles from 10-and 25-month-old animals were partially denervated by severing spinal nerve L5, and end plates were examined 4-7 and 10-14 days following denervation. Denervation induced a more profound increase in the percentage of end plates exhibiting ultraterminal sprouting in the 10- compared with 25-month-old animals. However, sprouting remained significantly greater in the 25- compared with the 10-month-old animals. Furthermore, following denervation the average ultraterminal sprout length was significantly greater in the 25- compared with the 10-month-old animals. There was no correlation between the extent of muscle denervation and the percentage of end plates exhibiting ultraterminal sprouts. End plates with ultraterminal sprouts had larger areas and contained fewer nerve terminal branches than end plates without these sprouts. It is suggested that the limited response to partial denervation in the 25-month-old extensor digitorum longus muscles may indicate that the aged extensor digitorum longus has already approached the maximum capacity for sprouting.

Animals↗
PubMed2006

Induction and recovery of colonic motility/defecatory disorders after extrinsic denervation of the colon and rectum in rats.

BACKGROUND: Anterior resection for rectal disease is associated with extrinsic autonomic denervation of the neorectum, which may influence the myenteric plexus, and subsequently the motility/defecatory status after operation. METHODS: A rat model with denervated neorectum was constructed. Colonic contractile activity in vivo, the amount of generic neuron marker (PGP 9.5) and nitric oxide synthase (NOS) were measured periodically. The responses of the muscle strip in each period to electrical field stimulation were evaluated using various neurotransmitters. RESULTS: In rats with denervated neorectum, giant migrating contractions (GMCs) of the distal colon, the number of fecal lumps per day and their small size, significantly increased in the early phase postoperatively, although both recovered in the late-phase period. The contractile response of the muscle strip of the denervated colon to acetylcholine was reduced throughout the period; however, contraction of the denervated colon under the addition of NO inhibitor (l-NAME) was enhanced significantly in the late-phase period, and recovered to the control level by atropine. Neuronal NOS, but not PGP 9.5 concentration, in the myenteric plexus at the distal denervated colon, significantly increased in the late-phase period. None of the above items differed from the control at other colonic portions throughout the period. CONCLUSIONS: Extrinsic autonomic denervation causes abnormal hyper-motility in the neorectum, which may be associated with multiple evacuations in the early phase postoperatively. Increased acetylcholine and the subsequent increase of neuronal NOS in the myenteric plexus may be an adaptive mechanism to compensate for such abnormal colonic motility after extrinsic denervation.

Animals↗
PubMed1998

Recovery of rat skeletal muscles after partial denervation is enhanced by treatment with nifedipine.

Following partial denervation of adult rat skeletal muscle intact axons sprout to reinnervate denervated muscle fibres and increase their territory. The extent of this increase is limited and may depend on the ability of axon terminals to form and maintain synaptic contacts with the denervated muscle fibres. Here we tested the possibility whether reducing Ca2+ entry into presynaptic nerve terminals through dihydropyridine sensitive channels may allow more nerve-muscle contacts to be formed and maintained. Hindlimb muscles of adult Wistar rats were partially denervated by removing a small segment of the L4 or L5 spinal nerve on one side. A nifedipine-containing silastic rubber strip was subsequently implanted close to the partially denervated soleus or extensor digitorum longus (EDL) muscles in some animals. In control experiments silastic strips which did not contain nifedipine were used. Several weeks later isometric contractions were recorded, to determine the effect of (a) partial denervation and (b) nifedipine treatment on force output and motor unit numbers. The tension produced by nifedipine treated partially denervated muscles was 82% and 79% of the unoperated contralateral value for soleus and EDL, respectively. This was significantly greater than in untreated muscles, which only produced 61% and 48%, respectively. Mean motor unit force was also significantly larger with nifedipine treatment. Histological analysis revealed that a significantly larger proportion of the total number of muscle fibres remained in nifedipine-treated partially denervated muscles (soleus, 90% and EDL, 101%) compared with untreated muscles (soleus, 51% and EDL, 66%). Thus the number of neuromuscular contacts was increased with nifedipine treatment.

Animals↗
PubMed1993

Effect of orthotopic transplantation and chemical denervation of the liver on hepatic hemodynamics in the rat.

The involvement of the sympathetic nervous system in the control of basal hepatic hemodynamics was investigated. Hepatic denervation was achieved by orthotopic transplantation or chemical denervation of the organ. In male Lewis rats, transplantation with rearterialization of the graft was performed. Chemical denervation was achieved by intraportal injection of 6-hydroxydopamine (75 mg/kg). Normal liver physiology was confirmed by histology and liver function tests. Four weeks post-transplantation and 7 days post-denervation, histological examination revealed no differences between transplanted, denervated and untreated or sham-operated control animals. Liver function measured by standard tests (e.g., plasma SGOT, bilirubin) was normal in all groups. The rate constants for aminopyrine breakdown in transplanted (0.015 +/- 0.005 min-1), denervated (0.015 +/- 0.0012 min-1) and control rats (0.015 +/- 0.001 min-1) were not significantly different. No significant difference in the rate of galactose breakdown was found. Total liver blood flow (measured by the 133Xe clearance technique in the anesthetized animal) was unaffected by transplantation (rate constant, 0.245 +/- 0.062 min-1; control 0.279 +/- 0.011 min-1). The interlobular distribution of portal blood flow was tested by intraportal injection of 51Cr-labelled microspheres. A linear relationship between flow to lobe and lobe size was confirmed in control (r = 0.95), denervated, (r = 0.99) and transplanted rats (r = 0.97) and the 'relative' flow to each lobe was not significantly different in the 3 groups. No significant differences in the 'core' to 'periphery' distribution of portal blood flow were found in the 3 groups. A small but significant portal systemic shunt was found in transplanted but not denervated or control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

Enlargement of motoneuron peripheral field following partial denervation with or without dorsal rhizotomy.

In partially denervated skeletal muscle, spared motor fibres sprout, enlarging motor unit size. Neuritogenesis and sprouting are known to depend on the synaptic input to the neurons. This suggests that spared motoneuron reaction to partial muscle denervation might be controlled by primary sensory neurons which directly or indirectly project to motoneurons. In two groups of rats, different surgical procedures were carried out: partial denervation of the extensor digitorum longus muscle without or with homolateral dorsal rhizotomy. Spared motoneuron peripheral field was evaluated by nerve-evoked tension measures. Following partial muscle denervation, spared motoneurons enlarged their projection peripheral field five to six times, innervating most of the denervated portion of the muscle. When dorsal rhizotomy was carried out together with partial denervation, the enlargement of the motoneuron's peripheral field occurred later; however, the peripheral field size was the same or greater than that found in partially denervated muscles without dorsal rhizotomy in the long term. Excitatory postsynaptic potential recordings at neuromuscular junctions consistently showed that innervation of denervated muscle cells by spared motoneurons was impaired when the dorsal roots were cut. Finally, in both groups of operated rats an increase in motor unit number occurred early after surgery, anticipating a process normally occurring in the same age range. These findings are consistent with the idea that sensory input trans-synaptically controls motoneuron peripheral field size.

Animals↗
PubMedDate not supplied

Paraspinal denervation and the spinal degenerative cascade.

BACKGROUND CONTEXT: The aging of the spine has been reported to follow a degenerative cascade described by Kirkaldy-Willis. This cascade does not take into account the paraspinal muscles. Substantial recent knowledge of the anatomy, physiology and pathophysiology of the paraspinal muscles suggests that they should play a role in the degenerative cascade. Pain relates to paraspinal denervation in a number of disorders. Using new needle electromyographic technique, MiniPM, we may be able to quantify the extent of paraspinal muscle denervation. PURPOSE: To explore the potential interactions between paraspinal muscle denervation and the degenerative cascade. STUDY DESIGN: Literature review, reanalysis of a blinded electromyographic study and case reports. PATIENT SAMPLE: A previously reported group of 35 asymptomatic paid volunteers, ages 18 to 58 years. Two elderly volunteers with moderate to severe spinal stenosis on magnetic resonance imaging (MRI), one significantly disabled, one asymptomatic. OUTCOME MEASURES: Blinded electromyographic testing, including MiniPM, a codified, quantified needle electromyography technique for the paraspinal muscles. In the two case reports, magnetic resonance imaging and 15-minute timed ambulation. METHODS: The 35 volunteers were tested by a blinded electromyographer using the MiniPM technique. The two older subjects underwent MRI, MiniPM and extensive electrodiagnostic evaluations, functional testing, complete history and physical examination. RESULTS: The patient with symptomatic stenosis had a MiniPM score of 6 on each side, and the asymptomatic volunteer had a score of 0. In the asymptomatic subject group, reproducible evidence for denervation was found in 20 subjects (57%), sparsely distributed, but more caudal than cranial (p<.0001). Based on conservative estimates of nerve regeneration rates, the population averaged a detected axonotemesis denervating event approximately once every 120 days. CONCLUSIONS: Paraspinal denervation may be proven to be a better marker than MRI findings for symptomatic spinal stenosis. Subtle paraspinal muscle denervation occurs frequently in asymptomatic persons. Whether a cause or an effect, paraspinal denervation might lead to hypermobility and thus progression along the degenerative cascade.

Adolescent↗
PubMed2000

The expression of the myogenic regulatory factors in denervated and normal muscles of different phenotypes.

The nerve is known to play a pivotal role in the diversification of muscle fibre types postnatally. Reducing neuronal activity in a slow muscle such as the soleus by denervation, switches on genes associated with a fast muscle phenotype. On the other hand, denervating a fast muscle such as the extensor digitorum longus (EDL) induces the conversion of fast fibres to a 'slower' contractile phenotype. The myogenic regulatory factors (MRFs) are proposed as the regulators of muscle phenotype as MyoD and myogenin have been shown to differentially accumulate in fast and slow muscle upon the induction of fibre type transformation. The denervation model has been used in the present study to induce changes in MRF expression in the muscles of the lower hindlimb which have distinct phenotypic characteristics. The level of MRF expression in pairs of denervated and innervated soleus, EDL, tibialis anterior (TA), plantaris and gastrocnemius muscles has been determined by Northern analysis and compared. The present study has shown that each muscle responds differently to denervation with respect to the increases in MRF expression. Fast muscles responded very quickly to denervation by increasing the level of MRF transcripts while slow muscles did not show significant increases in expression after 48 h denervation. The innervated EDL (fast) and soleus (slow) muscle differed with respect to the level of MRF-4 expressed, MRF-4 being expressed at higher levels in the slow muscle compared to the fast, suggesting that MRF-4 is important in the maintenance of a slow muscle phenotype. Moreover, MRF-4 and myogenin show the greatest fold increases in expression in the fast muscles examined. MyoD and Myf 5 show less dramatic increase in expression in response to denervation but exhibit the greatest fold increases in the fast muscles compared to slow.

Animals↗
PubMed2000

Denervation provokes greater reductions in insulin-stimulated glucose transport in muscle than severe diabetes.

We have examined the independent and combined effects of insulin insufficiency (streptozotocin (STZ)-induced diabetes, 85 mg/kg i.p.) and reduced muscle activity (denervation) (7 days) on basal, insulin-stimulated and contraction-stimulated glucose transport in rat muscles (soleus, red and white gastrocnemius). There were four treatments: control, denervated, diabetic, and denervated + diabetic muscles. Contraction-stimulated glucose transport was lowered (approximately 50%) (p < 0.05) to the same extent in all experimental groups. In contrast, there was a much smaller reduction insulin-stimulated glucose transport in muscles from diabetic animals (18-24% reduction, p < 0.05) than in denervated muscles (40-60% reduction, p < 0.05) and in denervated + diabetic muscles (40-60% reduction, p < 0.05). GLUT-4 mRNA reduction was greatest in denervated + diabetic muscles (approximately -75%, p < 0.05). GLUT-4 protein was decreased (p < 0.05) to a similar extent in all three experimental conditions (approximately -30-40%). In conclusion, (1) muscle inactivity (denervation) and STZ-induced diabetes had similar effects on reducing contraction-stimulated glucose transport, but (2) muscle inactivity (denervation), rather than severe diabetes, produced a 2-fold greater impairment in skeletal muscle insulin-stimulated glucose transport.

Animals↗
PubMed2003

Substance P enhances neuronal area and epithelial cell proliferation after colon denervation in rats.

We evaluated the neurotrophic effect of the neurokinin SP in the induced megacolon and the cell proliferation of the colonic epithelium after treatment. Colon segments of Wistar rats were chemically denervated by topical application of 2 mM benzalconium chloride and animals were daily injected intraperitoneally with SP (70 microg/kg body wt) for 15 days. Control rats received either SP or were denervated and treated with saline. Neuronal profiles of the myenteric plexus were studied by immunohistochemistry to motor protein myosin V and cell proliferation by PCNA immunolabeling. Denervation induced a significant reduction in the number of neurons and an enlargement of the surviving perikarya (from 263.7 microm2 in the control-saline group to 468.9 microm2 in the denervated groups). The total area occupied by neurons was maintained in the denarvated SP group but was significantly smaller in the denervated-saline group. The proliferative index was significantly higher in the denervated groups, of which the SP-treated group showed the highest index. These results suggest that SP may have a neurotrophic effect for the neurons of the myenteric plexus chemically denervated and that this denervation stimulates cell proliferation, especially after SP administration.

Animals↗
PubMed1983

Local regulation of compensatory noradrenergic hyperactivity in the partially denervated hippocampus.

Functional recovery after denervating lesions in the central nervous system (CNS) is particularly prominent if part of the lesioned projection is spared. Several plasticity mechanisms, such as collateral sprouting, hyperactivity of remaining axons and development of receptor supersensitivity, probably contribute to efficient recovery after subtotal lesions. Although denervation-induced collateral sprouting and presynaptic compensatory hyperactivity in spared axons have been described in various systems, any possible interaction or cooperation between the two mechanisms in restoring synaptic transmission in a partially denervated target has so far not been demonstrated. We have shown previously that partial adrenergic denervation of the hippocampus in adult rats is followed by a slow and protracted reinnervation by collateral sprouting from the spared adrenergic afferents. We now report that the partial adrenergic deafferentation is accompanied by a transient increase in turnover of the transmitter in remaining axons which subsides when the denervated region becomes reinnervated, and that the development of this compensatory hyperactivity is confined to the area of maximal denervation. The topographical specificity of the compensatory noradrenergic hyperactivity response, and the interaction between this hyperactivity and the collateral reinnervation process, strongly suggest that the changes in transmitter turnover in spared afferents after denervating lesions can be regulated by local mechanisms operating within the denervated target area.

Animals↗