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PubMed1976

[Influence of denervation on metabolism of phospholipid in the rat vas deferens].

Influence of denervation on phospholipid metabolism in the vas deferens and effect of phospholipase C treatment on sensitivity of the vas deferens for noradrenaline were studied. The incorporation of 32P-orthophosphate into phosphatidylethanolamine and phosphatidylcholine was markedly increased by denervation. Incorporation of 32P-orthophosphate into proteolipid was accelerated more than that of 3H-leucine. Sensitivity of the denervated vas deferens for noradrenaline was strongly reduced by phospholipase C treatment. These data suggest that the supersensitivity of the denervated vas deferens for noradrenaline was mainly due to the increase in phospholipids.

Animals↗

PubMed1990

Effects of various drugs on bladder function in conscious restrained-denervated rats placed in a restraining cage and produced by transection of the hypogastric nerve.

We evaluated the effects of various intravenously administered drugs, which had been shown to influence bladder function in anesthetized and/or conscious rats, on the cystometrogram in conscious restrained-denervated rats (produced by transection of the hypogastric nerve) placed in a restraining cage in comparison to those in conscious restrained-intact rats (with the hypogastric nerve intact) placed in a restraining cage. The bladder capacity in the restrained-denervated rats was smaller than that in restrained-intact rats and did not change when they were transferred to a wide cage, but the bladder capacity of the restrained-intact rats decreased following transfer to the wide cage. Therefore, the activity of the hypogastric nerve in conscious rats appears to be stimulated by restraint. Atropine suppressed the amplitude of the micturition contraction (time to micturition in the cystometrogram). In the restrained-denervated rats, thiopental and indomethacin increased the bladder capacity at almost the same doses as those in restrained-intact rats, but it took a higher dose of morphine to increase the bladder capacity than in restrained-intact rats. These findings suggest that cystometrography in restrained-denervated rats is a useful method for evaluating the effect of a newly developed agent on bladder function without any influence from the hypogastric nerve.

Animals↗

PubMed1998

Effects of alpha-isoproterenol on denervation atrophy in orbicularis oculi muscle fibers.

The effect of the beta-adrenoceptor agonist isoproterenol on the denervated orbicularis oculi muscle was studied. We cut the facial nerve on the right side of eight rats and injected isoproterenol (5 mg/kg) into four rats every day. The animals were sacrificed after three weeks, and small pieces of the orbicularis oculi muscle were removed. Muscle fibers were separated into single fibers. Cytochrome oxidase enzyme staining was applied, and density of cytochrome oxidase enzyme product and diameter of individual muscle fibers were analyzed by computer. Some of the muscle fibers were observed under electron microscopy. The results showed that diameter and cytochrome oxidase enzyme activity of the orbicularis oculi muscle decreased by denervation, otherwise, it increased to near the normal level by administration of isoproterenol. Electron microscopic observation showed that the myosion filaments became thin and their arrangement were disordered by denervation and their findings recovered to be almost normal by isoproterenol administration. We concluded that isoproterenol could prevent the orbicularis oculi muscle from atrophying which caused by denervation.

Animals↗

PubMedDate not supplied

Lipids associated with the (Na+ - K+)ATPase of normal and denervated electric organs of Electrophorus electricus (L.).

The effect of denervation on the lipid metabolism and on the activity of (Na+ - K+)ATPase isoforms from the membrane fraction P3, which corresponds to the innervated electrocyte membrane, was evaluated. On a discontinuous sucrose gradient, normal P3 membranes exhibit a bimodal ("a" and "b bands) distribution of the (Na+ - K+)ATPase activity, which upon denervation changes to an unimodal ("c" band) distribution. Using these fractions, which have a higher (Na+ - K+)ATPase activity, we characterized the lipids at the hydrophobic protein surface boundary, (i.e., the bulk lipids that surround the protein). The results confirm that these lipids consist of phospholipids and cholesterol. The quantitative composition of the phospholipids is similar for both isoform fractions obtained from the discontinuous gradient of normal membranes, with phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine representing about 90% of the total phospholipids. Sphingomyelin, phosphatidylinositol, diphosphatidylglycerol and phosphatidic acid were in the minority. However, in the single band obtained after denervation, the three major phospholipid components decreased to 70% of the total, and a significant increase in the other phospholipids and in cholesterol was observed. The high cholesterol content of the denervated fraction may confer membrane stabilization, as it is likely to cause a decrease in the membrane fluidity and consequently in the enzyme activity.

Acetylcholinesterase↗

PubMed2006

Induction of neuregulin signaling in mouse schwann cells in vivo mimics responses to denervation.

Neuregulins play crucial roles in early development of Schwann cells (SCs), but their roles in the activities of SCs during denervation and reinnervation of muscle are less clear. In the present study, the Tet-On system has been used in transgenic mice to enable inducible expression of a mutant, constitutively active neuregulin receptor (ErbB2) in SCs. This induction simulates neuregulin signaling to these cells. Reporter transgenes were used to show a tightly regulated, SC-selective expression in muscle. Induction leads to a number of changes in SCs at neuromuscular junctions that mimic the response to muscle denervation/reinnervation. These include process extension, soma migration, and proliferation. SCs also come to express nestin, a protein characteristic of their reaction to muscle denervation. This activation of SCs results in the sprouting of nerve terminals, and these sprouts follow the extensions of the SCs. However, these sprouts and their associated SCs disappear after the removal of the inducer. Last, induction of the active receptor is sufficient to rescue SCs in neonatal muscle from denervation-induced apoptosis. These findings show that the responses of SCs in muscle to denervation can be explained by induction of an autocrine/paracrine neuregulin signaling cascade suggested by previous molecular studies.

Animals↗

PubMed1985

Pregnancy and parturition in rats after sympathetic denervation of the ovary, oviduct and utero-tubal junction.

The ovarian vascular pedicle and ovarian suspensory ligament were briefly frozen to destroy the nerves. Examination of sections from the ovary, oviduct and utero-tubal junction by fluorescence histochemistry showed that they were usually devoid of adrenergic nerves. Measurement of noradrenaline in segments of the uterine horn by high-performance liquid chromatography showed that the transmitter was eliminated from the upper third but not the middle or lower thirds of the uterine horn. Unilateral or bilateral denervations at metoestrus in cyclic rats did not affect either the number of ovulations or the numbers or spacing of conceptuses at Day 7 of pregnancy. Bilateral denervations on Days 4, 7 or 11 of pregnancy did not affect ovarian weights or numbers of conceptuses observed 1 week later. Plasma progesterone concentrations were at least as high in the denervated groups as in the sham-operated control groups. After unilateral or bilateral denervations at Day 15, pregnancy continued normally and birth of normal young occurred, without apparent problems, at the same time as for sham-operated rats. The mothers tended their young and allowed them to suck. It is concluded that the adrenergic innervation of the ovary in the rat is not required for its normal function during pregnancy; that of the oviduct and mesosalpinx is not required for ovum pick-up or for transport of oocytes, spermatozoa or early embryos; and that of the utero-tubal junction is not required for uterine motility involved in embryo spacing and parturition.

Adrenergic Fibers↗

PubMed1984

Effect of denervation on the afferent arteriole in the SHR.

To study the role the renal nerves may play in the hypertension of the SHR, we conducted a morphometric study of the afferent arteriole of spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) which were subjected to renal denervation (or sham-operation). Methacrylate casts were made of the renal vasculature after perfusion fixation with glutaraldehyde. These vascular casts were then examined and measurements made with the scanning electron microscope (SEM). Afferent arterioles of the denervated SHR were dilated in comparison to the sham-operated SHR, but there was no difference between the afferent arteriolar diameters of the 2 groups of WKYs. However, the afferent arteriolar diameters of the SHR (either group) were smaller than those of the WKY. Renal denervation caused a reduction in systolic blood pressure compared to sham-operated in both strains of rat. We concluded that the dilation changes of afferent arterioles of denervated SHRs may be related to renal autoregulation resulting from the decreased blood pressure. However, the effect of the loss of sympathetic innervation of the arterioles cannot be ruled out.

Animals↗

PubMed2000

Choline acetyltransferase detection in normal and denervated electrocyte from Electrophorus electricus (L.) using a confocal scanning optical microscopy analysis.

Acetylcholine is the neurotransmitter responsible for the transmission of impulses from cholinergic neurons to cells of innervated tissues. Its biosynthesis is catalyzed by the enzyme Choline acetyltransferase that is considered to be a phenotypically specific marker for cholinergic system. It is well known that the regulation of Choline acetyltransferase activity under physiological and pathological conditions is important for development and neuronal activities of cholinergic functions. We observed the distribution of Choline acetyltransferase in sections from the normal and denervated main electric organ sections of Electrophorus electricus (L.) by immunofluorescence using a anti-Choline acetyltransferase antibody. The animals were submitted to a surgical procedure to remove about 20 nerves and after 30 and 60 days, they were sacrificed. After 30 days, the results from immunohistochemistry demonstrated an increase on the Choline acetyltransferase distribution at denervated tissue sections when compared with the sections from the normal contralateral organ. A very similar labeling was observed between normal and denervated tissue sections of the animals after 60 days. However, Choline acetyltransferase activity (nmolesACh/ min/ mg of protein) in extracts obtained from electrocyte microsomal preparation, estimated by Fonnun's method (Fonnun 1975), was 70% lower in the denervated extracts.

Animals↗

PubMed1998

Diverse effects of renal denervation on ventricular hypertrophy and blood pressure in DOCA-salt hypertensive rats.

Cardiac hypertrophy that accompanies hypertension seems to be a phenomenon of multifactorial origin whose development does not seem to depend on an increased pressure load alone, but also on local growth factors and cardioadrenergic activity. The aim of the present study was to determine if sympathetic renal denervation and its effects on arterial pressure level can prevent cardiac hypertrophy and if it can also delay the onset and attenuate the severity of deoxycorticosterone acetate (DOCA)-salt hypertension. DOCA-salt treatment was initiated in rats seven days after uninephrectomy and contralateral renal denervation or sham renal denervation. DOCA (15 mg/kg, s.c.) or vehicle (soybean oil, 0.25 ml per animal) was administered twice a week for two weeks. Rats treated with DOCA or vehicle (control) were provided drinking water containing 1% NaCl and 0.03% KCl. At the end of the treatment period, mean arterial pressure (MAP) and heart rate measurements were made in conscious animals. Under ether anesthesia, the heart was removed and the right and left ventricles (including the septum) were separated and weighted. DOCA-salt treatment produced a significant increase in left ventricular weight/body weight (LVW/BW) ratio (2.44 +/- 0.09 mg/g) and right ventricular weight/body weight (RVW/BW) ratio (0.53 +/- 0.01 mg/g) compared to control (1.92 +/- 0.04 and 0.48 +/- 0.01 mg/g, respectively) rats. MAP was significantly higher (39%) in DOCA-salt rats. Renal denervation prevented (P > 0.05) the development of hypertension in DOCA-salt rats but did not prevent the increase in LVW/BW (2.27 +/- 0.03 mg/g) and RVW/BW (0.52 +/- 0.01 mg/g). We have shown that the increase in arterial pressure level is not responsible for cardiac hypertrophy, which may be more related to other events associated with DOCA-salt hypertension, such as an increase in cardiac sympathetic activity.

Animals↗

PubMed1988

Relation of prognosis of peripheral facial nerve palsy to the period between onset of illness and date of denervation.

The presence or absence of the denervation is one of the important factors to determine the prognosis of peripheral facial nerve palsy and it is generally accepted that the denervation becomes apparent within 2 weeks from the onset of illness. In the present study, 62 cases with denervation in which nerve excitability test (NET) was possible within 1 week from the onset of illness were selected for analysis. Although 47 cases exhibited the denervation within 2 weeks, it was first detected after 2 weeks in other 15. Although the prognosis was far better in the latter group, 2 cases exhibited the unfavorable recovery. These results indicate the importance of NET even 2 weeks after the onset of illness.

Denervation↗

PubMed2003

Expression of BDNF and TrkB in mouse taste buds after denervation and in circumvallate papillae during development.

BDNF (brain-derived neurotrophic factor) is a member of the neurotrophin family which affects the proliferation and survival of neurons. Using an immunocytochemical method, we examined the expression of BDNF and its receptor, TrkB, in the taste bud cells of the circumvallate papillae of normal mice and of mice after transection of the glossopharyngeal nerves. We additionally observed the expression of BDNF and TrkB in the developing circumvallate papillae of late prenatal and early postnatal mice. In normal untreated mice, BDNF was expressed in most of the taste bud cells; TrkB was detected in the plasma membrane of taste bud cells and in the nerve fibers. Double-labeling studies showed that BDNF and NCAM (neural cell adhesion molecule) or TrkB and NCAM colocalized in some of the taste bud cells, but that most taste bud cells were immunopositive for only BDNF or TrkB. NCAM-immunoreactive cells are known to be type-III cells, which have afferent synaptic contacts with the nerve terminals. Five days after denervation, the number of taste buds and nerve fibers markedly decreased; however, the remaining taste bud cells still expressed BDNF and TrkB. By 10 days after denervation, most of the taste buds had disappeared, and there were a few TrkB-immunoreactive nerve fibers in the connective tissue core. By 4 weeks after denervation, numerous TrkB-immunoreactive nerve fibers had invaded the papillae, and a few taste buds expressing BDNF and TrkB had regenerated. At E (embryonic day) 15 during development, the circumvallate papillae appeared, and then TrkB-immunoreactive nerve fibers entered the connective tissue core, and some of these fibers further invaded among the dorsal epithelial cells of the papillae. TrkB-immunoreactive oval-shaped cells were occasionally found in the dorsal epithelium. Such TrkB-immunoreactive nerve fibers and cells were also observed at E16-18. However, BDNF was not expressed in the papillae through the late prenatal days of E15 to E18. At P (postnatal day) 0, a cluster of BDNF-and TrkB-immunoreactive cells appeared in the dorsal epithelium of the papillae, and was presumed to be primitive taste buds. We conclude that TrkB-immunoreactive nerve fibers are necessary for papillary and taste bud formation during development and for the regeneration of taste buds after denervation. BDNF in the taste bud cells may act as a neurotrophic factor for innervating sensory neurons--through TrkB receptors of the axons of those neurons, and also may exert autocrine and paracrine trophic actions on neighboring taste bud cells by binding to their TrkB receptors.

Animals↗

PubMed1979

Morphological and morphometric studies with the electron microscope on the Merkel cells and associated nerve terminals of normal and denervated skin.

Merkel cells and associated nerve endings of dog snout skin as well as foot and toe pads of rats were studied with the transmission electron microscope. Normal Merkel cells are characterized by the following morphological features: 1) localization restricted to the basal layer of the epidermis, 2) adjoining afferent nerve endings containing many mitochondria, 3) specific small round granules usually accumulated in the cytoplasm on one side of the nucleus facing the junction of the nerve ending, 4) highly lobulated irregular shape of the nucleus, 5) well developed Golgi apparatus with a few immature granules situated on the side of the nucleus opposite the junction at the ending, 6) spine-like processes extending from the cell surface where no nerve endings abut, 7) desmosomes and desmosome-like membrane thickening on the cell surface both abutting the surrounding keratinocytes and the nerve endings. The Merkel cells with nerve endings were observed and measured at various days after denervation. The experiments were carried out on rats whose sciatic nerves were transected. The samples of skin of foot and toe pads of the denervated legs were taken almost every day from 1 to 30 days. Almost no changes were noticed after 24 hrs, but within the next day the nerves retracted and were no longer observed in the epidermis. The Merkel cell granules increased in number in 1--3 days but decreased again to about a half of the value of the control at 30 days. The polarity of granules distribution showing a strong accumulation in the cytoplasm near the nerve ending became less marked after denervation. Some cells sustained severe degeneration in the later stage of experiment. It was remarkable that the activity of Merkel cells might depend on the associated nerves, but they never completely disappeared even after a long period of denervation.

Animals↗

PubMed1979

Denervated muscle: rate of propagation and effects of manganese ions and glycerol on the fibrillatory activity of frog semitendinosus.

Denervated frog's semitendinosus muscles were studied. Fibrillation potentials generate propagated spikes which are conducted at a rate similar to that calculated for innervated muscles. The twitch tension per unit area was similar in denervated and innervated single fibres; the average value corresponded with values reported in the literature for fibres stimulated at 125/sec. Manganese ions (1-3 mM), selectively inhibit fibrillation potentials and have no appreciable effect upon evoked spikes. Mn2+ also inhibits (40-50%) the twitch responses and abolishes the resting tension of muscle fibres. The latter effects were observed in denervated as well as in innervated preparations when the fibres studied belonged to fasicles located at the site of entrance of the nerve. Disruption of the transverse tubular system by glycerol treatment does not interfere with the generation of fibrillation potentials, although the effects on twitching are similar to those reported in the literature. A possible mechanism is proposed to explain the generation of fibrillation potentials in frog denervated muscles.

Animals↗

PubMed1991

Ultrastructural and histochemical study of the neuromuscular junctions in the denervated intrinsic laryngeal muscle of the cat.

Morphological changes and acetylcholinesterase (AchE) activity in the neuromuscular junctions (NMJ) of the normal and denervated posterior cricoarytenoid muscle (PCA muscle) of the cat were studied. Two days after denervation, the nerve terminals at the NMJ had almost disappeared. Six weeks after denervation, intensity of AchE activity at the former junctional site (FJS) was unchanged histochemically. At this stage, primary synaptic clefts were distorted and the Schwann's cells covered the FJS. Fourteen weeks after denervation, AchE activity at the FJS had decreased in contrast to that of the non-affected side. Calcitonin gene-related peptide (CGRP) was also investigated at the NMJ of the normal PCA muscles immunocytochemically. The present study shows that CGRP coexists with Ach in the nerve terminals of the PCA muscles and may be involved in the regulation of the contractile function of the intrinsic laryngeal muscle.

Acetylcholinesterase↗

PubMed1980

Comparison of physiological and pharmacological stimulation of acid secretion in vagally innervated and denervated gastric pouches in the same dog.

The double-pouch dog with one vagally innervated Amdrup pouch (AP) taken from the lesser curvature side of the stomach and one denervated Heidenhain pouch (HP) from the corporo-fundic part permitted comparison of gastric secretion from innervated and denervated mucosa at the same time in the same animal. Food stimulation with a mixture of liver, heart, and bonemeal showed significantly higher response from AP than from HP for all doses, and the difference between the pouches in total acid output was constant for all doses, indicating that the relative contribution of vagal innervation is diminished when the size of the protein meal is increased. The difference between innervated and denervated mucosa is achieved by an immediate high response from the AP. After 150 min the responses to the larger meals were identical in the two pouches. Acid output during stimulation with pentagastrin reached 64.4% of maximal response to histamine in the AP and 36.2% in the HP, the innervated mucosa giving a statistically significant higher response for all doses. Absence of innervation gave an HP response similar to non-competitive inhibition with significantly lower calculated maximal response and a CD50 not different from the CD50 for the AP. Twenty-four hour secretion studies during optimal physiological conditions with the dog fed two daily meals of standard composition showed sparse secretion from denervated mucosa, whereas a great part of the capacity of innervated mucosa is utilized during daily conditions.

Animals↗

PubMed1990

Acute effects of total or partial digit denervation on raccoon somatosensory cortex.

The immediate effects of total or partial denervation of single digits (0-16 hr after nerve transection) on primary somatosensory cortex were studied electrophysiologically. Comparisons of response properties and cortical somatotopy were made between intact raccoons and four groups of raccoons with transection of some or all of the nerves innervating the fourth or fifth digit. Animals with all four digital nerves cut (amputation of the digit) were most different from normal. Approximately half of the penetrations in the affected cortical region showed inhibitory responses to stimulation of adjacent skin regions. These consisted of a strong response to stimulus offset and/or a suppression of spontaneous activity during indentation. Since these responses were substantially different from those recorded several months after digit amputation, additional changes in connectivity and synaptic strength must occur with chronic denervation. These inhibitory responses were not seen in animals with one, two, or three nerves cut per digit. In the animals with partial denervation of a digit, the greatest disruption occurred when both ventral nerves to the glabrous skin were transected. This yielded cell clusters with abnormally large receptive fields, disruptions in somatotopic organization, and a decreased occurrence of low-threshold responses. If only one nerve to glabrous skin was transected, there was less change, even if it was combined with transection of both nerves to hairy skin. These results suggest that the release of inhibitory responses in a cortical digital region by amputation is prevented by the retention of even one ventral nerve. None of the denervation conditions produced large nonresponsive areas of cortex, which would have indicated a loss of all inputs.

Afferent Pathways↗

PubMed1993

The immediate effects of peripheral denervation on inhibitory mechanisms in the somatosensory thalamus.

Multiunit recordings were made in the ventroposterior lateral nucleus of the thalamus in anesthetized raccoons. During recording from cells responding to cutaneous stimulation of a forepaw digit, the corresponding digit was denervated permanently (by cutting its four digital nerves) or temporarily (by injecting lidocaine into the base of the digit). Both procedures resulted in immediate increases in the inhibition that could be induced by stimulation of the adjacent digits when the original cutaneous receptive field was on the glabrous skin. In each case with temporary denervation, this enhanced off-focus inhibition decreased when the excitatory responses returned to normal. In contrast, temporary denervation of the digit during recording at sites in the hairy skin representation did not reveal this increased inhibition from adjacent digits. When capsaicin was applied to the digital nerves in two animals, the excitatory receptive fields of thalamic neurons increased in area, but were still restricted to the same part of the digit. These data indicate that the immediate unmasking of inhibitory responses, previously reported in primary somatosensory cortex of the raccoon, is also present in the thalamus. The capsaicin-induced expansion of excitatory receptive fields confirms previous experiments in other species, and suggests that C fibers play a role in modulating the size of cutaneous receptive fields. However, the enlargement of excitatory receptive fields by capsaicin is much less than the unmasking of inhibitory fields induced by digit denervation, and indicates that different mechanisms are involved in controlling these various inputs to thalamic neurons.

Afferent Pathways↗

PubMed1985

Specific increase in renal alpha 1-adrenergic receptors following unilateral renal denervation.

The effect of unilateral surgical renal denervation on adrenergic receptors in rat kidney was investigated. Denervation was performed by mechanically stripping the nerves from the renal artery and then painting with phenol. This procedure resulted in a decrease in norepinephrine content to less than 10% of the contralateral kidney. The concentrations of alpha 1-, alpha 2-, beta 1- and beta 2-adrenergic receptors were measured in both kidneys of rats 1 week following left renal denervation. Alpha 1-receptor concentrations increased in the denervated left kidneys relative to the intact right kidneys. Alpha 2-, beta 1- and beta 2-receptor concentrations were not different between left and right kidneys. These results indicate that the different classes of adrenergic receptor in the kidney are differentially regulated by agonist stimulation.

Animals↗