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PubMed1987

Effect of parasympathetic denervation on K+ release by rat parotid slices.

1. By measuring the release of 86Rb, potassium movement was compared in parasympathectomized (Px) and contralateral control parotid gland slices three weeks following surgical denervation. 2. Carbachol and phenylephrine elicited a biphasic increase in 86Rb release that was dose related and could be blocked by atropine and phentolamine respectively. The transient phase was of 2-4 min duration and Ca independent whereas the sustained phase of 86Rb release was greatly reduced by the omission of the external Ca. 3. Denervation caused a shift to the left of the 86Rb efflux dose-response curve to carbachol and phenylephrine (3.75- and 3.37-fold respectively). Pilocarpine had similar action to carbachol but it behaved as a partial agonist. 4. Parasympathectomy (Px) increased the intrinsic activity of the partial agonist pilocarpine and converted it to a full agonist. Results of the present study indicate the possibility of an altered receptor-signal transduction mechanism between the receptor and phospholipid turnover/Ca mobilization in the denervated rat parotid gland.

Animals↗
PubMed1984

Reinnervation of the rat touch dome restores the Merkel cell population reduced after denervation.

By using the fluorescent dye quinacrine as a marker for the Merkel cells in the rat touch dome, we previously showed that a sustained denervation of the dome causes a rapid and persistent loss of about 60% of its Merkel cells [Nurse, Macintyre and Diamond (1984) Neuroscience 11, 521-533]. We now show that if the sensory nerves to the skin are crushed (or cut) in 2-week old pups and allowed to regenerate, the Merkel cell population within touch domes shows a biphasic response; there is an initial loss of Merkel cells associated with the early phase of denervation, followed by an increase, associated with the phase of reinnervation. Physiological tests revealed that many (though not all) domes within initially deafferented skin had become functionally reinnervated and had their Merkel cell numbers either wholly or partially restored some 40-100 days post operatively. In one case an adult reinnervated dome, that appeared normal physiologically and by its complement of quinacrine fluorescent (Merkel) cells, also had normal histological features in toluidine blue sections and normally innervated Merkel cells in the electron microscope. These results, based on the use of quinacrine to visualize the Merkel cell population in the touch dome, suggest that sensory nerves may induce the differentiation of new Merkel cells in domes where these cells have become reduced after denervation.

Animals↗
PubMed1988

Neuropeptide Y- and alpha-adrenergic receptors in pig spleen: localization, binding characteristics, cyclic AMP effects and functional responses in control and denervated animals.

The localization of neuropeptide Y binding sites in the pig spleen, as revealed by [125I]Bolton-Hunter-labelled porcine neuropeptide Y and alpha 1-adrenergic receptor binding sites, as revealed by [125I](2-beta/4-hydroxy-phenyl/-ethylaminomethyl)-tetralone as radioligand, was compared with the distribution of neuropeptide Y and noradrenaline nerves, the latter revealed by tyrosine hydroxylase and dopamine-beta-hydroxylase, using immunohistochemistry. A large degree of codistribution was obtained between [125I]neuropeptide Y and alpha 1-binding sites in the capsule, trabeculae, blood vessels and the red pulp of the spleen. Neuropeptide Y and tyrosine hydroxylase as well as dopamine-beta-hydroxylase-positive nerves were identical in the spleen and had a similar gross distribution pattern as the [125I]neuropeptide Y and alpha 1 binding sites. In functional studies using the isolated blood-perfused spleen from pentobarbital-anaesthetized pigs, neuropeptide Y, noradrenaline and the alpha 1-selective agonist phenylephrine contracted the capsule and induced vasoconstriction in the spleen in vivo. However, the selective alpha 2-adrenoceptor agonists clonidine and azepexole had no effects on blood flow or perfusion pressure, suggesting that postjunctional alpha-receptors were of the alpha 1 type. Neuropeptide Y inhibited the forskolin-evoked, cyclic adenosine monophosphate formation in vitro. The [125I]neuropeptide Y binding, with an equilibrium-dissociation constant of 503 +/- 73 pM and a maximal number of specific binding sites of 23 +/- 3 fmol/mg protein, the neuropeptide Y-induced perfusion-pressure increase in vivo and the inhibition of forskolin-evoked cyclic adenosine monophosphate formation in vitro were dependent on the amidation of the C-terminal portion of the peptide molecule. Furthermore, the effects of neuropeptide Y were not changed by alpha- and beta-adrenoceptor blockade using prazosin and propranolol. Two weeks after postganglionic denervation the neuropeptide Y and the noradrenaline contents of the pig spleen were reduced by 97% and 99%, respectively. These changes were associated with a selective supersensitivity for the noradrenaline-induced perfusion-pressure increase in vivo compared with the effect of neuropeptide Y. However, a similar potentiation of the noradrenaline effect was induced by the monoamine-uptake blocker desipramine in the absence of denervation, and there was no change in the functional response to phenylephrine after denervation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Schizophrenia and tardive dyskinesia: is schizophrenia also a "denervation hypersensitivity"?

In human beings, amphetamine can induce both schizophreniform psychosis and oral-facial dyskinesia resembling tardive dyskinesia, while neuroleptic agents reduce the manifestations of both conditions. This suggests that such psychosis and movement disorder may occur by the same or very similar mechanisms. It is thought that tardive dyskinesia may result from neuroleptic-induced denervation hypersensitivity to dopamine. The author cites evidence suggesting that amphetamine may act on dopaminergic pathways in the CNS to produce a denervation hypersensitivity like that caused by neuroleptic agents. Clinical evidence compatible with a denervation hypersensitivity hypothesis of schizophrenia is then discussed.

Animals↗
PubMed1983

Long-term unilateral noradrenergic denervation: monoamine content and 3H-prazosin binding sites in rat neocortex.

Direct biochemical determinations of alpha 1 adrenoceptor sites were performed in the neocortex of rats subjected to a selective unilateral noradrenergic deafferentation, obtained by microinjecting 6-OHDA in the right dorsal noradrenergic bundle (DNB). After 3 months survival the alpha 1 sites were assayed using 3H-Prazosin (3H-PRZ), in both the denervated and the contralateral (control) cortex. The catecholamines dopamine (DA), epinephrine (EPI), norepinephrine (NE), as well as the indoleamine serotonin (5-HT) were measured using radioenzymatic assays in samples of the frontal cortex of these same animals, as well as in the septum and hippocampus in order to assess the extent and specificity of the deafferentation. The results document that unilateral NE-deafferentations of the cerebral cortex are feasable, the reduction in NE persists for at least three months, and there is an increased endogenous DA content. In the denervated cerebral cortex specific binding of 3H-PRZ showed an increase (+ 45%) in the density of receptor sites (Bmax) without any changes in the dissociation constant (KD 25 degrees C). The results have to be considered in relation both to plasticity changes in monoamine fibers and to denervation-induced alterations of the postysynaptic alpha-adrenoceptors.

Afferent Pathways↗
PubMed1993

Up-regulation of beta 2-adrenergic receptors in previously transplanted, denervated nonfailing human hearts.

OBJECTIVES: The purpose of this study was to examine beta-adrenergic receptor signal transduction in denervated, previously transplanted human ventricular myocardium. BACKGROUND: In model systems, surgical denervation typically results in both presynaptic and postsynaptic supersensitivity in beta-adrenergic receptor pathways and alteration in G protein-mediated signal transduction. METHODS: We examined beta-adrenergic receptor signal transduction in the left and right ventricles removed from nine subjects with a previous transplant and surgical denervation 25 +/- 4 months after their first transplantation. Twenty-six hearts removed from organ donors served as control hearts. RESULTS: Total beta-adrenergic receptor density and stimulation of muscle contraction in isolated right ventricular trabeculae by the nonselective agonist isoproterenol were similar in the transplant and donor groups. Beta 1-receptor density was not different in the left ventricles of the two groups but tended to be reduced (by 29%, p = 0.09) in transplant right ventricles. By contrast, beta 2-receptor density was higher in transplant left and right ventricles relative to the respective values in donor ventricles by 33% in left ventricles and 97% in right ventricles (both p < 0.05). Isoproterenol, which in particulate fractions of human heart stimulates adenylyl cyclase primarily via beta 2-receptors, produced a greater increase in cyclic adenosine monophosphate generation in membranes prepared from transplant left ventricles and right ventricles compared with donors. In contrast, guanosine 5'-[beta,gamma-imido]triphosphate, sodium fluoride and forskolin, which stimulate adenylyl cyclase through nonreceptor/G protein-sensitive mechanisms, yielded similar degrees of adenylyl cyclase stimulation in the two groups, and both pertussis toxin- and cholera toxin-catalyzed adenosine diphosphate ribosylation were not altered in transplanted left ventricles. CONCLUSIONS: These data indicate that the transplanted human heart exhibits an up-regulation of functional beta 2-adrenergic receptors.

Adenylyl Cyclases↗
PubMed1995

The ability to re-express polysialylated NCAM in soleus muscle after denervation is reduced in aged rats compared to young adult rats.

The neural cell-adhesion molecule, NCAM, contains an unusual homopolymer of sialic acid units, polysialic acid. This carbohydrate seems to be involved in neurite outgrowth, bundling and branching, processes which are important during reinnervation. In aged rats, reinnervation of denervated muscle fibres is incomplete. In this study, age-related changes in the degree of polysialylation of NCAM re-expressed after denervation were examined using a monoclonal antibody recognizing polysialic acid and a polyclonal antibody recognizing NCAM. The results show that, after denervation, the degree of polysialylation on NCAM was clearly reduced in rat soleus muscle of aged, compared to young, adult rats. This age-related change in expression of polysialic acid probably influences the reinnervation process in aged muscle.

Animals↗
PubMed1988

Structural alterations in the membrane of the slow muscle fiber of Rana temporaria after denervation.

Mixed fiber bundles as well as separated slow and fast fibers from normal and denervated muscles of Rana temporaria were freeze-fractured. The membranes of both fiber types are distinguished in this species by the presence of fairly regularly distributed particle aggregates or arrays of different shapes and sizes; the number per unit area of the membrane is six times higher in fast than in slow fibers. The intramembrane particle (IMP) density is higher in slow than in fast fibers. After denervation, the fast fiber membrane structure does not change whereas the slow fiber membrane acquires the characteristics of the fast fiber, i.e., an increase in the density of particle arrays and a decrease in IMP density. These changes in the slow fiber membrane are compared to the altered physiological properties of this fiber type after denervation.

Animals↗
PubMed1988

Immunological evidence for a change in subunits of the acetylcholine receptor in developing and denervated rat muscle.

We used specific antibodies to gamma, delta, and epsilon subunits to characterize acetylcholine receptor (AChR) in extracts and at endplates of developing, adult, and denervated rat muscle. The AChRs in normal adult muscle were immunoprecipitated by anti-epsilon and anti-delta, but not by anti-gamma antibodies, whereas AChRs in denervated and embryonic muscles were precipitated by anti-gamma and anti-delta, but showed little or no reactivity to anti-epsilon antibodies. In immunofluorescence experiments, AChRs at neonatal endplates bound antibodies to gamma or delta, but not epsilon, subunit, whereas those in adult muscles bound antibodies to epsilon or delta, but not gamma, subunit. AChRs at denervated endplates and at developing endplates between postnatal days 9 and 16 bound all three antibodies. We conclude that the distribution of gamma and epsilon subunits of the AChR parallels the distribution of AChRs with embryonic and adult channel properties, respectively.

Animals↗
PubMed1990

Primary structure and expression of a sodium channel characteristic of denervated and immature rat skeletal muscle.

The alpha subunit of a voltage-sensitive sodium channel characteristic of denervated rat skeletal muscle was cloned and characterized. The cDNA encodes a 2018 amino acid protein (SkM2) that is homologous to other recently cloned sodium channels, including a tetrodotoxin (TTX)-sensitive sodium channel from rat skeletal muscle (SkM1). The SkM2 protein is no more homologous to SkM1 than to the rat brain sodium channels and differs notably from SkM1 in having a longer cytoplasmic loop joining domains 1 and 2. Steady-state mRNA levels for SkM1 and SkM2 are regulated differently during development and following denervation: the SkM2 mRNA level is highest in early development, when TTX-insensitive channels predominate, but declines rapidly with age as SkM1 mRNA increases; SkM2 mRNA is not detectable in normally innervated adult skeletal muscle but increases greater than 100-fold after denervation; rat cardiac muscle has abundant SkM2 mRNA but no detectable SkM1 message. These findings suggest that SkM2 is a TTX-insensitive sodium channel expressed in both skeletal and cardiac muscle.

Amino Acid Sequence↗
PubMed1992

Cardiac denervation in the calf using cryoablation: functional evidence and regional tissue catecholamine content.

Twenty-six calves were subjected to a technique of cryoablation in order to establish an animal model of complete cardiac denervation. All 26 survived the procedure, and 20 were alive to be re-evaluated 2-4 weeks later. Mean heart rate in the denervated animals rose from 77 +/- 7.8 beats/min to 102 +/- 16.4 (P less than 0.01). Cryoablation abolished the heart rate responses to electrical stimulation of the vagus nerve and thoracic sympathetic trunk. The reduction in myocardial noradrenaline concentrations averaged 99% in the right atrium, 90% in the left atrium, 85% in the right ventricle and 90% in the left ventricle, when compared with tissue obtained from control animals. Cryoablation is a relatively simple means of accomplishing complete functional cardiac denervation in the calf. On the basis of the observed change in heart rate, the calf model appears to be more comparable with human heart transplant recipients than the dog.

Animals↗
PubMed1985

Prevention and treatment of sciatic denervation disuse osteoporosis in the rat tibia with capacitively coupled electrical stimulation.

Osteoporosis in the sciatic-denervated rat tibia was both prevented and reversed with a capacitively coupled electrical field. In both the prevention of the development of osteoporosis and the reversal of a previously established osteoporosis, a statistically significant enhancement of wet weight, dry weight, ashed weight, ultimate strength, cortical area, cortical thickness, and a concomitant decrease in cortical porosity occurred in the stimulated, denervated tibiae of the experimental animals compared with the nonstimulated, denervated tibiae of the control animals. These effects exhibited dose-response characteristics. A 60 kHz symmetrical sinewave signal was effective in preventing osteoporosis at a range of 5-10 peak-to-peak, and it was effective in reversing osteoporosis at 10 V peak-to-peak. Reversal of a well-established osteoporosis in laboratory animals has not been reported previously. Continued investigation into the use of a capacitively coupled electrical field in the prevention and treatment of osteoporosis seems warranted from these studies.

Animals↗
PubMed2004

Effect of periurethral denervation on smooth muscles of the lower urinary tract.

OBJECTIVE: This study was undertaken to determine the effect of periurethral denervation on contractile function of the smooth muscle of the lower urinary tract of the female rat. STUDY DESIGN: Periurethral nerve transection or sham operation was performed in 35 young female rats. Contractile function of the bladder dome and base was determined as a function of time after surgery. Statistical analysis was conducted by Student t test. RESULTS: Periurethral denervation resulted in impaired contractile responses to electrical field stimulation in the bladder base (nerve-transected 45 +/- 11 g/cm 2 ; sham 84 +/- 10 g/cm 2 , P < .05) and dome (nerve-transected 179 +/- 16 g/cm 2 ; sham 334 +/- 29 g/cm 2 , P < .05) 2 weeks after nerve transection. The ability to respond to potassium chloride and the muscarinic agonist, carbachol, and the rates of contraction and relaxation, however, remained intact. Baseline phasic contractile activity was increased significantly in bladders from nerve-transected animals. Maximal field-stimulated contractions of the longitudinal urethra smooth muscle were not altered by periurethral denervation (sham 21 +/- 6 g/cm 2 , nerve-transected 19 +/- 5 g/cm 2 , P = .4). Compromised nerve-mediated contractions of the bladder dome and base improved significantly by 21 days. CONCLUSION: Periurethral nerve transection results in transient impairment of neurogenic contractile responses in the bladder base and dome, though the intrinsic ability of the bladder to contract remains intact. This compromised response of the dome, in conjunction with previous results demonstrating impaired urethral smooth muscle relaxation, suggests that transection of periurethral neurons may have complex effects on the entire lower urinary tract.

Animals↗
PubMed2005

Strengthening of partially denervated knee extensors using percutaneous electric stimulation in a young man with spinal cord injury.

OBJECTIVE: To evaluate the effects of percutaneous electric stimulation on knee extensor strength and muscle hypertrophy, gait, and energy cost of walking in a young man with partial denervation of the knee extensors. DESIGN: One-way repeated measures. SETTING: Pediatric orthopedic hospital. PARTICIPANT: A man in his early twenties, who had an L2 American Spinal Injury Association class D spinal cord injury, presented with strength deficits in his left knee extensors and reported falling frequently. When walking, his left knee remained locked in extension throughout stance. Electromyographic testing revealed chronic denervation and reinnervation changes. INTERVENTION: Because of sensory difficulties with surface stimulation, a percutaneous electrode was surgically implanted near the femoral nerve. The subject exercised isometrically with a research grade stimulator for 1 hour a day until his strength plateaued. MAIN OUTCOME MEASURES: Quadriceps femoris strength and hypertrophy, gait, and energy cost of walking were recorded preintervention, every 2 months during the strengthening phase, and 2 months after withdrawal. RESULTS: Voluntary isometric torque improved from 7 to 14.8Nm (112%) and decreased to 8.5Nm after stimulation was withdrawn. Mean circumferential measures of the thigh improved from 12.3 to 13.5cm (9.8%) and then decreased to 13.1cm. Gait kinematics and kinetics were unchanged, although the subject reported greater stability in his left knee and fewer falls. CONCLUSIONS: The study indicates that percutaneous electric stimulation could be used to strengthen partially denervated muscle and to affect function. However, gains in strength may not be maintained once treatment is withdrawn.

Adult↗
PubMed2005

Time-dependent regional myocardial denervation as a nonspecific response to transmyocardial laser revascularization.

BACKGROUND: It is known that denervation occurs in the regions of myocardium treated by laser transmyocardial revascularization (TMR). The purpose of this study was to determine when regional denervation occurs in the early postoperative period and whether or not it is specific to laser TMR when compared with TMR using ultrasonically activated energy. METHODS: Dogs with normal myocardium underwent either holmium:yttrium-aluminum-garnet laser TMR, TMR using an ultrasonic activated surgical blade, or a thoracotomy as sham operation. The responses of mean arterial pressure to topical application of bradykinin were examined at 3 time points: before, 1 hour after, and 2 weeks after surgery. The hearts were excised for Western blot and immunohistochemical analysis. RESULTS: The response of mean arterial pressure to bradykinin was similarly attenuated in both TMR groups 1 hour after treatment and decreased to almost none after 2 weeks compared with pretreatment values. By comparison, the sham group showed persistent responses at both time points. Tissue tyrosine hydroxylase content of the treated area decreased significantly compared with the non-treated area in both TMR groups. Immunohistochemistry using anti-Protein Gene Product 9.5 and anti-synaptophysin antibodies showed a significant decrease in the number of positive nerve fibers in both TMR treatment groups compared with the sham group. CONCLUSIONS: Transmyocardial revascularization caused partial alteration in myocardial innervation immediately after TMR. Tissue responses may continue to occur for the first 2 weeks after treatment. Tissue responses may also contribute to the development of denervation regardless of the energy source in non-ischemic canine myocardium.

Animals↗
PubMed2006

Study of skeletal muscle glycogenolysis and glycolysis in chronic steroid myopathy, non-steroid histochemical type-2 fiber atrophy, and denervation.

OBJECTIVE: Muscle biopsies from chronic steroid (glucocorticoid) myopathy, non-steroid histochemical type-2 fiber atrophy, and muscle denervation patients were studied to determine if their glycogen contents, or enzymes involved in glycogenolysis and glycolysis might be related to their fiber atrophy. DESIGN AND METHODS: Fast frozen muscle biopsies from the above patients and from patients later judged by histochemistry to be normal were assayed enzymatically for glycogen content, for enzymes involved in glycogenolysis, and for 6 of the enzymes involved in glycolysis. RESULTS AND CONCLUSION: All three groups of patients had glycogen content, but only the chronic steroid myopathy muscle had statistically less glycogen content than did normal human muscle. All 3 groups had statistically low mean values compared to normal muscles for glycogen phosphorylase activity. This suggests that the biosynthesis and phosphorolysis of glycogen are not involved in muscle fiber atrophy, and glucocorticoid administration does not activate muscle glycogen biosynthesis. Histochemical type-2 fiber atrophy muscles were low compared to normal muscles in three glycogenolysis enzyme activities plus four glycolysis enzyme activities. Muscles from denervation patients were low compared to normal muscles in three glycogenolysis enzyme activities plus five glycolysis enzyme activities. This suggests that muscle denervation may lower the rate of glycolysis enough to fail to provide sufficient pyruvate for mitochondrial ATP biosynthesis, resulting in insufficient protein biosynthesis in both fiber types.

Adult↗
PubMed2005

Adaptive expression pattern of different proteins involved in cellular calcium homeostasis in denervated rat vas deferens.

The activity and protein expression of plasma membrane and sarco(endo)plasmic reticulum (Ca2+-Mg2+)ATPases and ryanodine receptors were investigated in surgically denervated rat vas deferens. The function of thapsigargin-sensitive but not thapsigargin-resistant (Ca2+-Mg2+)ATPase (from sarco(endo)plasmic reticulum and plasma membrane, respectively), evidenced by enzyme activity and Ca2+ uptake experiments, was significantly depressed by 30-50% when compared to innervated vas. Western blots showed that such reduction in sarco(endo)plasmic reticulum (Ca2+-Mg2+)ATPase performance was accompanied by a decrement of similar magnitude in sarco(endo)plasmic reticulum (Ca2+-Mg2+)ATPase type 2 protein expression, without any significant change in plasma membrane (Ca2+-Mg2+)ATPase expression. Finally, [3H]ryanodine binding revealed that the density of ryanodine binding sites was reduced by 45% after denervation without modification in affinity. The present findings demonstrate that sarco(endo)plasmic reticulum proteins involved in intracellular calcium homeostasis are clearly down-regulated and brings further evidence of a modified calcium translocation in denervated rat vas deferens.

Animals↗
PubMed2006

Innervation of the wrist joint and surgical perspectives of denervation.

PURPOSE: Because our experience with the techniques used in denervation surgery of the wrist joint often has proven insufficient in treating chronic pain we conducted an anatomic study to clarify the exact contributions of the nerves supplying the wrist joint. Our goal was to reveal all periosteal and capsular nerve connections and if necessary adjust our technique used in denervation surgery. METHODS: Innervation of the wrist joint was investigated by microdissection and histologic examination of 18 human wrists. An acetylcholinesterase method was used to identify the nerves, both in whole-mount preparations and in sections. RESULTS: We found that the main innervation to the wrist capsule and periosteal nerve network came from the anterior interosseous nerve, lateral antebrachial cutaneous nerve, and posterior interosseous nerve. The palmar cutaneous branch of the median nerve, the deep branch of the ulnar nerve, the superficial branch of the radial nerve, and the dorsal branch of the ulnar nerve also were found to have connections with the capsule. The periosteal nerve branches did not appear to play a major role in the innervation of the capsule and ligaments; here the specific articular nerve branches proved more important. The posterior and medial antebrachial cutaneous nerves did not connect to the wrist capsule or periosteum but rather terminated in the extensor and flexor retinaculum. CONCLUSIONS: Based on our findings we propose to denervate the wrist by making 2 incisions. With one palmar and one dorsal incision it should be possible to disconnect the periosteum from the capsule and interrupt the majority of the capsular nerve branches.

Acetylcholinesterase↗