Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DENERVATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 559 records · Page 31Linked to original sources
PubMed1975

Influences of chronic denervation of the carotid bifurcation regions on panting in the sheep.

The respiratory response of conscious sheep subjected to severe heat stress has been assessed before and up to 17 weeks after bilateral denervation of the carotid bifurcations. The characteristic response of the intact animal comprises an initial phase of rapid, shallow panting, superseded by panting of a slower, deeper form which results in a severe respiratory alkalosis; this was not significantly altered by the denervation. However, during recovery from heat stress, denervated animals developed a marked hypoxaemia and tachycardia. Blood pressure was much more labile in denervated animals. After denervation, resting arterial PCO2 was higher, PO2 was lower, and blood pressure and heart rate were higher; with the lapse of weeks, these parameters returned towards pre-denervation levels although the carotid bodies remained inactive. It is concluded that the carotid bodies do not play a significant role in control of the biphasic pattern of panting during severe heat stress, but that they normally prevent post-hyperventilation hypocapnic hypoxaemia during recovery. Further, the respiratory pattern during heat stress is the results of an overwhelming thermoregulatory drive, whereas the pattern during recovery is the result of a balance between arterial and medullary chemoreceptor activity, Finally, the carotid bodies normally play a significant role in determining the 'set-point' for CO2 regulation, but in their absence respiratory control mechanism adapt over a considerable time period.

Animals↗
PubMed1985

Excitation-contraction coupling and contractile properties in denervated rat EDL and soleus muscles.

The long-term (up to ten weeks) effects of denervation on isometric tension and potassium (K) contractures were studied in isolated bundles of fibres from rat extensor digitorum longus (EDL) and soleus muscles, at 21 degrees C, bathed in solutions with low concentrations of chloride ions (to reduce the effects of high membrane chloride conductance). The usual increases in twitch time course and twitch for tetanus ratio were attributed to changes in excitation-contraction coupling because both developed between one to three weeks after denervation. Transient changes during the first week in the time course of the twitch and twitch to tetanus ratio in EDL, and post-tetanic twitch size and specific tension in both muscles, were attributed to the surface membrane electrical properties which are maximally altered within three days after denervation. In contrast to results obtained in solutions of normal chloride concentration, the resting membrane potentials of chronically denervated fibres were hyperpolarized and spontaneous action potentials and fibrillations were seen. The time to the peak of the K-contracture was faster than normal and very slow inactivation kinetics appeared in the decay phase. Mechanical repriming was normally slower in EDL than in soleus but similar rates were seen in the two muscles after denervation. These changes in the K-contracture were not due to a change in the relationship between membrane potential and potassium ion concentration. It is concluded that denervation caused changes in the kinetics of mechanical activation, inactivation and repriming and that these aspects of excitation-contraction coupling are normally controlled by an influence of the motor nerve.

Animals↗
PubMed1985

The distribution of acetylcholine receptors in the normal and denervated neuromuscular junction of the frog.

A combined light and electron microscopic investigation was performed to study the distribution and fate of clusters of horseradish peroxidase (HRP)-labelled or rhodamine-labelled alpha-bungarotoxin binding sites in normal and denervated cutaneous pectoris muscles of the frog. After staining for axon and cholinesterase (ChE) it appears that, in normal muscles, binding sites for rhodamine alpha-bungarotoxin are strictly confined to those parts of the synaptic gutter occupied by the nerve terminal. Binding sites are missing in axon-abandoned gutters or gutters occupied only by the Schwann cell. Similarly, in partially occupied gutters, HRP-toxin binding sites are confined to the parts of the muscle fibre membrane apposed to the nerve; they are missing at axon-free lateral parts at which secondary clefts and ChE are present. These observations suggest that junctional acetylcholine (ACh) receptor clusters are strictly controlled by the nerve. Thirty-five days after denervation, receptor density was apparently reduced in some parts of the gutters while other parts of the same gutters showed high receptor density. In addition, the length of gutter totally devoid of receptor clusters increased from an average fraction of 9% in control muscles to 14% in denervated muscles. Loss of receptors occurred both at Schwann cell-free and at Schwann cell-occupied gutters. In muscles denervated for 500-750 days, no toxin binding sites could be detected in the junctional membrane, whereas ChE was still present. Schwann cells had apparently abandoned some gutters but were present at others. Upon arrival of spontaneously reinnervating axons, muscle fibres accumulate ACh receptor clusters at the junctional membrane. Patches intensely labelled with alpha-bungarotoxin and associated with ChE reaction product were found near former junctions in long-term denervated muscles. It is concluded that after long-term denervation the muscle fibre cannot maintain junctional ACh receptor clusters by itself. In normally innervated muscles, receptor clusters are actively maintained by nerve-borne factors near the transmitter release sites.

Animals↗
PubMed1982

Effect of denervation on 'synaptic' ribbon populations in the rat pineal gland.

The formation of pineal 'synaptic' ribbons (SR) may be directly related to the adrenergic innervation of the gland. In order to clarify this relationship, SR populations at various times from 12 h to 14 days after pineal denervation were morphometrically analysed by electron microscopy. Pineal denervation was accomplished by bilateral superior cervical ganglionectomy. A decrease in nocturnal pineal SR numbers, indicating a reduction in SR formation, was demonstrated 12 to 24 h after pineal denervation. Seventy-two hours after ganglionectomy SR numbers were comparable with those in nocturnal intact and sham-operated controls. Thereafter, 7 and 14 days after ganglionectomy, SR numbers exceeded nocturnal intact and sham-operated controls. Administration of isoproterenol, a beta-adrenergic receptor agonist, 24 h after denervation significantly increased SR numbers over those in untreated rats denervated 24 h earlier. Thus SR formation remained responsive to adrenergic receptor stimulation in the absence of an intact adrenergic innervation. Further, the increase in SR numbers following subacute (7 to 14 days) denervation indicated that SR formation was not dependent on an intact innervation or the presence of endogenous (pineal) norepinephrine. On the basis of these results, we suggest that SR formation may be related structurally as well as functionally to adrenergic receptors on the rat pinealocyte.

Animals↗
PubMed1982

Denervation modulated changes in mouse skeletal muscle RNA concentration.

We have examined normal and denervated mouse skeletal muscle for histological evidence of changes in RNA concentration using acridine orange/nucleic acid fluorescence. In denervated muscle, cytoplasmic RNA concentration increases dramatically. The earliest increase is in the subsarcolemmal region, 7 days after denervation. By 28 days after denervation, the increase in RNA is distributed throughout the cytoplasm of the atrophic cells, non-atrophic cells show little or no increase. Prior to the increase in cytoplasmic RNA concentration, many myocyte nuclei exhibit enlarged nucleoli, indicative of active ribosomal RNA synthesis. Such active nucleoli are present throughout the 42 day study period. We conclude that both new RNA synthesis, and preferential accumulation of cytoplasmic RNA are prominent events in denervation atrophy. There is an ordered progression from nucleolar synthesis to subsarcolemmal accumulation to diffuse accumulation in atrophying cells. These observations complement biochemical findings of others which indicate an increase in both RNA and protein synthesis after denervation.

Animals↗
PubMed2026

The miR-206-3p/Cpeb1 axis delays acetylcholine receptor degradation and preserves neuromuscular junction stability in denervation-induced muscle atrophy.

Peripheral nerve injury leads to progressive neuromuscular junction (NMJ) destabilization and acetylcholine receptor (AChR) degradation, which are critical drivers of denervation-induced muscle atrophy and impaired motor recovery. However, the post-transcriptional mechanisms regulating AChR stability during denervation remain poorly understood. Here, we investigated the role of miR-206-3p in NMJ maintenance and muscle preservation after denervation, with a focus on its interaction with the RNA-binding protein cytoplasmic polyadenylation element binding protein 1 (Cpeb1). Using C2C12 myoblasts and a sciatic nerve transection mouse model, we demonstrate that miR-206-3p promotes myogenic differentiation, enhances AChR clustering, and preserves postsynaptic AChR morphology. miR-206-3p directly targets the 3' untranslated region of Cpeb1, suppressing its expression, as confirmed by dual-luciferase reporter assays. In vivo, adeno-associated virus-mediated overexpression of miR-206-3p delayed denervation-induced AChR fragmentation, attenuated muscle atrophy, and significantly improved motor function recovery. Conversely, Cpeb1 overexpression accelerated AChR degradation and muscle wasting, whereas co-overexpression of miR-206-3p mitigated these detrimental effects, indicating that Cpeb1 is a key downstream effector of miR-206-3p. Collectively, our findings identify the miR-206-3p/Cpeb1 axis as a previously unrecognized regulator of NMJ stability and muscle integrity after denervation, providing mechanistic insight and a potential therapeutic target for preserving neuromuscular function during prolonged denervation.

Animals↗
PubMed2002

Rescue of motoneurones by MK-801 innervating partially denervated rat muscles.

Partial denervation of the extensor digitorum longus muscle by cutting the L4 spinal nerve in 3-day-old rats causes some of the remaining uninjured motoneurones to die. A previous study has shown that of the 12 motor units usually present in the remaining uninjured L5 spinal nerve, a significantly smaller number of motor units to extensor digitorum longus muscle is found in animals operated on at 3 days. This reduction can be caused by a greater sensitivity of neonatal motoneurones with axons in a partially denervated muscle, to excitotoxic effects of glutamate. Therefore an N-methyl- D-aspartic acid (NMDA) receptor antagonist, MK-801, was injected daily for 12 days after partial denervation at 3 days. Two months after the operation contractile properties, motor unit numbers and sizes were studied. Following MK-801 treatment, the reduction in muscle weight and force output of the partially denervated muscle was less than that in the untreated group. Moreover there were more motor units in MK-801 treated animals. After partial denervation only, 15% of the total number of motor units was present whereas when the same operation was followed by treatment with MK-801, 29% remained. The mean motor unit size in the untreated group was 69% while after treatment with MK-801 it was 152% of the control. Thus treatment with MK-801 after partial denervation of neonatal animals rescued some of the motoneurones destined to die, and allowed expansion of motor unit territory of most of the surviving motoneurones.

Animals↗
PubMed1997

Early effects of denervation on sarcoplasmic reticulum properties of slow-twitch rat muscle fibres.

The Ca2+ release activity of the sarcoplasmic reticulum (SR) in chemically skinned single slow-twitch fibres from control, 2-day and 7-day denervated rat soleus muscle was studied. Histochemical fibre type composition of the whole muscle, electrophysiological properties and the Ca2+ sensitivity of tension development by single muscle fibres were also studied. All the data were correlated with contractile properties of the in vitro muscle. In the 2-day denervated muscle the SR Ca2+ capacity and the rate of Ca2+ uptake decreased from the control values of 0.384 +/- 0.030 micromol (mg fibre protein)-1 and 19.8 +/- 1.9 nmol min-1 (mg fibre protein)-1, respectively, to 0.210 +/- 0.016 micromol (mg fibre protein)-1 and 13.5 +/- 0.9 nmol min-1 (mg fibre protein)-1; the calculated amount of Ca2+ released upon stimulation by caffeine decreased from the control value of 0.148 to 0.078 micromol (mg fibre protein)-1. In the 7-day denervated muscle, the SR Ca2+ capacity and the rate of Ca2+ uptake increased to 0.517 +/- 0.06 micromol (mg fibre protein)-1 and 21.6 +/- 2.3 nmol min-1 (mg fibre protein)-1, respectively; the calculated amount of Ca2+ released increased to 0.217 micromol (mg fibre protein)-1. Both contraction time and tension of the isometric twitch decreased in 2-day denervated and increased in 7-day denervated muscles. Electrophysiological and histochemical changes, as well as changes in the Ca2+ sensitivity of the muscle fibres did not show any apparent correlation with mechanical changes. It is therefore concluded that the SR plays a prominent role in the early changes of contraction time and tension following denervation.

Animals↗
PubMed1997

The developmental skeletal growth in the rat foot is reduced after denervation.

It has long been known that bone is innervated. In recent years it has been suggested that the local nerves may influence the growth and metabolism of bone by way of neuropeptides. The transient local presence of nerve-containing cartilage canals just before formation of secondary ossification centres in rat knee epiphyses seems to support that view. The purpose of the present study was to see if denervation affects the developmental growth of metatarsal bones in the rat hindfoot. We made sciatic and femoral neurectomies in 7-day-old rat pups and examined the hindfeet at various times after surgery. Immunohistochemical analysis showed that denervation was complete. Radiographic examination revealed that the metatarsal bones were significantly shorter in denervated hindfeet 30 days after denervation (average relative shortening 9.9 +/- 2.3%). Measurements of total foot length showed that denervated feet were subnormally sized already five days postoperatively, before the onset of secondary ossification. The timing of the latter was not affected by denervation. Control rats subjected to tenotomies exhibited normal metatarsal bone lengths. On the basis of these results we suggest that the local nerves may influence the growth of immature bones but do not affect secondary ossification.

Animals↗
PubMed1993

Persistence and calcium-dependent ATPase staining of denervated fungiform taste buds in the hamster.

Some fungiform taste buds in the hamster have been previously shown to persist for indefinite periods when deprived of their gustatory, chorda tympani (CT), innervation or both their CT and their trigeminal, lingual nerve, innervation (CT-L). The properties and numbers of persisting fungiform taste buds were examined 1 or 3 weeks after permanent CT or combined CT-L nerve cuts. The purpose was to reveal the status of taste buds at a time (3 weeks) when regenerating nerve fibres would normally be expected to reinnervate the epithelium. Denervated taste buds retain many normal characteristics including the pattern of histochemical staining for ectocalcium-dependent ATPase (Ca-ATPase). Taste-bud cells (including basal cells) have an intensely Ca-ATPase stained core surrounded by lightly stained peripheral cells. The Ca-ATPase stain was used to help identify and to define the size of the taste-bud core in denervated taste buds. Following CT-L or CT denervation most taste buds persisted; however the size of the taste-bud core was dramatically reduced. Fungiform taste buds differed in size based on their location in one of three tongue regions. The percentage decrease in size after denervation was also region specific and about the same for CT-L or CT cuts, suggesting that trigeminal fibres have no trophic effect on taste buds. However, trigeminal denervation caused a reduction in the number of persisting taste buds relative to CT denervation alone, which may be due to damage because of the loss of somatosensation.

Animals↗
PubMed1982

Importance of pathway formation for nodal sprout production in partly denervated muscles.

Experiments were carried out to investigate possible factors controlling nodal sprout growth in partly denervated mouse gluteal muscles. Pretreatment of the muscle with botulinum toxin for up to 20 days, which produces denervation-like change and elicits terminal and nodal sprouting, increased reinnervation by terminal sprouting after partial denervation but did not alter the rate of reinnervation by nodal sprouts. This implies that nodal sprout growth is not limited by the development of an adequate growth stimulus from denervated muscle. A disto-proximal gradient of degeneration was observed in denervated intramuscular nerves in the electron microscope, suggesting that nodal sprout growth may be modulated by the availability of endoneurial pathways sufficiently degenerated to permit reinnervation by nodal sprouts, although the initial outgrowths from nodes of Ranvier may appear in response to a growth stimulus from denervated muscle.

Animals↗
PubMed1985

Distribution of motor nerve sproutings in the mouse gastrocnemius muscle after partial denervation.

The distribution and frequency of motor nerve sproutings in the mouse gastrocnemius muscle were examined after a partial denervation. Terminal and nodal sproutings could be seen for a period of 7-28 days after transecting one of the two muscular nerves in the medial head. They grew out not only from the endplates and terminal nerves, but also from the preterminal nerve regions of both the intra- and extramuscular nerve. The terminal sproutings originated from endplates close to the denervated portion and subsequently they were seen farther away in the medial head. Upon regeneration of the originally transected nerve the terminal sproutings were withdrawn in the reverse sequence, i.e., first from the region farthest from the denervated area and last from the region adjacent to the denervation. The frequency of terminal sproutings was constant in the area immediately bordering the denervated portion (11-15% of the total number of endplates). In other areas more distant from the denervated portion, however, it showed a gradient which varied with the time course. The higher the frequency of terminal sproutings, the more actively each endplate produced two or three terminal sproutings without significant difference in length.

Animals↗
PubMed1994

Evidence for volume transmission in the dopamine denervated neostriatum of the rat after a unilateral nigral 6-OHDA microinjection. Studies with systemic D-amphetamine treatment.

In the present study the hypothesis has been tested if the dopamine releasing drug D-amphetamine via volume transmission can, at least partly, restore dopamine communication in the dopaminergically denervated neostriatum of rats. The experimental model used, has been a unilateral 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine neurons, based on nigral microinjections of this neurotoxin. Studies on c-fos like immunoreactivity after systemic D-amphetamine treatment demonstrated a wide-spread appearance of c-fos like immunoreactive neuronal nuclear profiles within the neostriatum on both the unlesioned and denervated side. In the unlesioned neostriatum a peak density of c-fos like immunoreactive profiles was found within the central part of the neostriatum, while on the denervated side the distribution pattern of c-fos like immunoreactive profiles peaked medially and gradually declined in a lateral direction. The microdialysis experiments demonstrated, after systemic d-amphetamine treatment, a marked and sustained increase of extracellular dopamine levels in the neostriatum on the unlesioned side, while no increases in the extracellular dopamine levels were observed on the dopaminergically denervated neostriatum. In the electrophysiological experiments, systemic D-amphetamine treatment produced an inhibition of the neuronal activity on the denervated side which showed a significant increase in basal discharge rate compared with the recordings obtained from the striata on the unlesioned side. The present immunocytochemical microdialysis and electrophysiological analysis provides evidence that in the unilaterally markedly dopamine depleted neostriatum with clearcut signs of dopamine receptor supersensitivity (rotational behaviour results), dopamine transmission may be partly restored via systemic D-amphetamine treatment through the release of dopamine, predominantly from the unlesioned neostriatum, which may diffuse into the cerebrospinal fluid to reach the contralateral dopaminergically denervated neostriatum.

Animals↗
PubMed1994

Central alpha 1- and alpha 2-adrenoceptors and brain cholinergic stimulation in sinoaortic denervated rats.

The central alpha-adrenoceptor role in cardiovascular responses to intracerebroventricular (i.c.v.) injection of neostigmine, a tertiary anticholinesterase, was studied in conscious sham-operated and sinoaortic-denervated rats. Neostigmine (0.1-1 micrograms i.c.v.) showed dose-dependent pressor and bradycardiac effects in vehicle-pretreated sham-operated rats but only an increased pressor effect in sinoaortic-denervated animals. The pretreatment with the catecholaminergic neurotoxin, 6-hydroxydopamine (250 micrograms i.c.v.), given 72 h previous to the corresponding operation, blunted the cardiovascular effects of neostigmine in both groups of rats. Prazosin (10 and 30 micrograms i.c.v.), an alpha 1-adrenoceptor antagonist, prevented the pressor response to neostigmine (0.3 micrograms i.c.v.) in sham-operated and sinoaortic-denervated rats. Yohimbine, a alpha 2-adrenoceptor antagonist (10 and 30 micrograms i.c.v.), only prevented the bradycardia induced by neostigmine (0.3 micrograms i.c.v.) in the sham-operated rats. 6-Hydroxydopamine pretreatment lowered the norepinephrine content in hypothalamus, midbrain, medulla oblongata and spinal cord, but did not modify it in the pons, in sham-operated rats and sinoaortic-denervated animals. The present results suggested that brain alpha 1-adrenoceptors would mediate the pressor response to neostigmine (i.c.v.) in sham-operated and sinoaortic-denervated rats and central alpha 2-adrenoceptors mediate the bradycardia in sham-operated rats. This work lends support to the view that cardiovascular responses to brain cholinergic stimulation in sham-operated and sinoaortic-denervated rats could be mediated by a central catecholaminergic activation.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1984

Increased activities of MB and BB isozymes of creatine kinase in denervated neonatal and adult rat muscle.

Creatine kinase (CK) activity and isozyme patterns were assessed in newborn and adult rat anterior tibial muscle in response to denervation. Total CK activity was low in the control neonatal muscle, gradually increasing to the adult level within 1 month. Denervation prevented this normal increase, and, therefore, CK activity was reduced to 25% of control at 2 months. In the denervated adult muscle, total CK activity decreased to 50% of control within 3 weeks and remained at that level. Denervation of neonatal muscle resulted in a greater conservation of MB isozyme compared with controls. The alteration in BB isozyme expression was even more dramatic with a 33-fold difference expressed at 2 months in terms of percent total CK in denervated vs. control muscle. In denervated adult muscle, MB and BB isozyme activities increased gradually, attaining levels 3-fold and 13-fold, respectively, above control muscle at the end of the experimental period.

Aging↗
PubMed1986

Reinnervation and recovery of cat muscle receptors after long-term denervation.

After nerve injury muscles remain denervated until axons return to begin reinnervation and recovery. The delay between injury and recovery in human limb nerves averages 13 weeks after crush, and 16 weeks after transection and suture. In order to assess the effects of such long denervation periods on the recovery of cat muscle receptors, we crushed the common peroneal nerve and denervated peroneus brevis for 10 to 134 days; 39 days were allowed for reinnervation in each experiment. After 50 days denervation, the mean number of terminal bands in the regenerated spindle primary endings was 10.3 compared with a normal mean of 29.0. After 134 days, the mean was 0.6 and spindles were severely atrophied. Despite this most spindle afferent fibers continued to respond normally to ramp-and-hold stretch, abnormal responses being recognized as those that failed to maintain firing during the held phase of the ramp. After 50 days, 21% of spindle afferent fibers responded abnormally and about this proportion did so after all the longer denervation periods. Maximum afferent firing rates were all significantly lower than normal, and many afferent fibers fatigued more rapidly. Tendon organs were atrophied after 113 and 134 days and received fewer terminals, but their afferents fired apparently normally during muscle twitch. These results imply that the consequences of long-term denervation on human muscle spindles would be unlikely to affect the overall pattern of response to stretch of any Ia or II afferent fibers reinnervating them, though the quality of their response might be impaired.

Afferent Pathways↗
PubMed1987

Trophic control of cholinesterase activity in a testosterone-dependent muscle of the rat: effects of castration and denervation.

The effects of testosterone withdrawal and chronic denervation on muscle weight and acetylcholinesterase (AChE) activity were studied in the hormone-sensitive levator ani muscle of the rat. Castration of adult male rats for 7 to 60 days caused a linear decrease of the weight, protein content, and AChE activity of the muscle, which stabilized after 30 days. Muscle weight and protein content decreased 2.3% per day. The total AChE activity decreased 7 days later 3.2% per day, reaching 37% of control at day 30. AChE activity per unit weight was increased in all castrated groups. Muscle weights and AChE activity of the extensor digitorum longus and soleus muscles were not altered after castration. Denervation of all three muscles caused 50% reduction of the muscle weight and protein content after 15 days. Total AChE activity decayed exponentially with a rate of 0.12 per day to 15 to 18% of control values. AChE activity per unit weight in the denervated muscles was always lower than in the control muscles. Combined castration and denervation intensified only the levator ani protein loss. The different onset and time course of the effects induced by castration and denervation indicate distinct mechanisms involved in the trophic control of muscle proteins and AChE activity. Chronic muscle denervation decreased total AChE activity to 15% of normal, whereas castration reduced the enzyme to 40% of the control values. The results indicate that neuronal and hormonal influences on AChE activity of the levator ani are not additive but overlap.

Acetylcholinesterase↗
PubMed1987

Caffeine contractures in denervated slow-twitch and fast-twitch muscles of the rat.

Caffeine contractures (25 mM) and twitches were registered in vitro (34 degrees C) in normal and denervated soleus and extensor digitorum longus of the rat. Both muscles lost weight progressively after denervation although the loss of weight in soleus muscles was more manifest. Denervated extensor digitorum longus muscles showed an increase in the caffeine contracture tension (expressed in g/g muscle) whereas the response generated by denervated soleus muscles was smaller than the control values. The time to peak of the caffeine responses was shortened in both types of muscles after denervation. Twitches were larger and had a slower time course than in normal muscles, especially in the extensor digitorum longus muscles. These findings suggest that some changes in the excitation-contraction coupling could be responsible for the potentiation of the twitches in denervated muscles.

Animals↗