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Adaptive responsiveness of some central receptors to the denervation of heterologous afferent fibers: functional significance and possible behavioral consequences.

As shown in the rat brain, the development of the classical "denervation supersensitivity" of receptors does not always occur despite the complete destruction of the corresponding afferent fibers. This is due to the concomitant destruction of heterologous fibers which directly or indirectly contribute to the regulation of the denervated receptors. In this review, on the basis of data obtained in rats with lesions of ascending DA neurons, three examples of hetero-regulation of receptors will be provided. In the prefrontal cortex, the concomitant destruction of afferent noradrenergic fibers (NA) prevents the development of the denervation supersensitivity of DA receptors of the D1 type. In the nucleus accumbens, the development of the denervation supersensitivity of D1 receptors seems to be dependent on the state of activity of the cortico-nucleus accumbens glutamatergic projection. Finally, in cortico-limbic structures, the prolonged interruption of DA transmission leads to an increased density of 125I-neurotensin binding sites. These hetero-regulations reflect the existence of possible functional relationships between the two types of neuronal populations under investigation. As an example, it will be shown that some dysfunctions seen following the degeneration of the mesocortico-prefrontal and mesolimbic DA neurons disappear following the combined destruction of ascending NA neurons.

Adrenergic Fibers↗

AMP-deaminase activity in denervation atrophy of the amphibian skeletal muscle.

The substrate (AMP) and co-factor (ATP)-dependent kinetic parameters of AMP-deaminase have been studied in the contralateral and denervated gastrocnemius muscles of frog, Rana hexadactyla. An increasing in apparent affinity (Km) and maximal velocity (V) were found with denervated muscle enzyme as compared to the contralateral muscle enzyme. The activation energy (delta E) values were found to be decreased on denervation suggesting increased catalytic efficiency of denervated muscle enzyme.

AMP Deaminase↗

Effects of selective denervation and nerve growth factor on activity-mediated growth of rat parotid gland.

A dietary change from all liquid to solid food is followed by an average increase of 200% in [3H]thymidine uptake into the parotid gland of rat. However, removal of either the parasympathetic (Px) or the sympathetic (Sx) innervation to the parotid gland prior to the dietary change resulted in a partial inhibition of the increase; values for the parasympathectomized gland were 51% of those of the innervated gland, and values of the sympathectomized parotid gland were 42% of those of the innervated gland. Removal of both autonomic nerves caused a complete inhibition. Initiation of nerve growth factor (NGF) injection (1 microgram/kg body wt, two times daily for the 2 days of chow refeeding) at the time of chow refeeding had no effect on completely or partially denervated glands, and thymidine values for the denervated parotid gland of rats given NGF did not differ statistically from those of rats not given NGF. With parasympathectomy, sympathectomy, and complete denervation, weight of parotid gland was decreased from that of innervated glands, and administration of NGF had no effect on the denervation-induced decreases. The data show that both branches of the innervation to parotid gland must be intact to ensure a maximal increase in thymidine uptake with the dietary change from liquid to solid food. The level of the enzyme, beta 1-4 galactosyltransferase, involved in proliferation, also depended on the presence of intact nerves. Enzyme activity of innervated parotid gland showed an average increase of 200% with chow refeeding of rats previously on liquid diet, but with Px, the average increase was 51% of that of the innervated parotid, and with Sx, it was 41%. NGF administration did not cause any change in levels of this enzyme in any Px or PxSx parotid gland and only a small change in Sx parotid; it did increase levels of this enzyme in parotid of rats without submandibular-sublingual glands.

Animals↗

[Selective peripheral denervation for spasmodic torticollis involving the levator scapulae muscle].

Patients with laterocollis or rotatory type torticollis tend to show abnormal contraction of the levator scapulae muscle and the scalene muscles. These muscles are innervated from the anterior branches of the cervical spinal nerves. Because of this, the traditional Bertrand operation dealing with posterior branches does not adequately affect the symptoms of laterocollis. The authors report selective denervation of the levator scapulae muscle in three patients and discuss its rationale. All the three patients underwent denervation of both the C1-C6 posterior spinal rami and the branches from the C3 and C4 anterior rami to the levator scapulae muscle. We added myotomy of the scalene muscle in one patient, and denervation of the omohyoid muscle which is innervated from the ansa cervicalis and the descending branch of the hypoglossal nerve. The pre/post-operative Tsui scores were 12/4, 15/1, and 14/3 respectively. There were no complications. We conclude that selective peripheral denervation of the levator scapulae muscle is safe and effective in the treatment of laterocollic type torticollis.

Adult↗

Upregulation and redistribution of cadherins reveal specific glial and muscle cell phenotypes during wallerian degeneration and muscle denervation in the mouse.

In the present work, we investigated the expression of cadherin mRNAs in the adult neuromuscular system either under normal conditions or following experimental neurotomy. Cadherin-6, a marker of Schwann cell precursors, was not expressed in the adult peripheral nerve, while M-cadherin, cadherin-11, and N-cadherin were expressed both by glial and conjunctive cells. Moreover, the three transcripts were transiently upregulated in the distal stump of neurotomized sciatic nerve during Wallerian degeneration: N-cadherin was abundant in myelinating Schwann cells during myelin degradation, while M-cadherin and cadherin-11 may be upregulated in proliferating Schwann cells. M-cadherin, cadherin-11, and N-cadherin were also detected in myofibres and endomysium of adult gastrocnemius muscle. Following neurotomy, cadherin-11 was only transiently increased in denervated myofibres, while M-cadherin was increased and sustained for at least 21 days postoperation. In contrast, N-cadherin was not upregulated in denervated myofibres. Thus, we defined here a combination of cadherins expressed in the adult nerve and muscle, and modulated during Wallerian degeneration and muscle denervation. The comparison of the expression pattern of this combination of cadherins to the one previously described during embryonic development shows that chronically denervated Schwann and muscle cells do not reverse to embryonic state (recapitulative hypothesis), but present specific phenotypic features.

Animals↗

[Power measurement of denervated muscle isografts with neurorrhaphy and nerve-implantation in rats].

The hypothesis was tested in this experiment that after 7 months of predencervation, the reinnervation of muscle grafts with neurorrhaphy results in greater recovery of force and power than with nerve-implantation. In a highly inbred strain of rats, soleus muscles were isografted. The donor muscles were either immediately denervated at the time of isografting or denervated 2, 4, 7 months prior to isografting. Soleus muscles from each donor group were transplanted into the right legs of hosts with either epineurial anastomosis (NR group) or nerve implantation (NI group). The contralateral soleus muscles of hosts served as controls. Sixty days after transfer, both right and left soleus grafts/muscles were evaluated for force and power measured in situ. The absolute force values were significant higher in NR group (61% of normal) than in NI group (40% of normal) in 2-month group but the result invenrsted in 7-month group, less than 20% and more than 20% of normal in NR and NI groups respectively. The reduced ability of grafts to generate force and power resulted from the different ways of reinnervation in denervated muscles and the period of predenervation. Maybe the nerve-implantation is better than the neurorrhaphy for reinnervating a long-term denervated muscle.

Anastomosis, Surgical↗

[Response of the granulation tissue to acetylcholine and noradrenaline during denervation].

Granulation tissue from the wounds of back of both paws was studied in rats on 7th day of healing following crushing of right sciatic nerve and after repeated applications of 0.2 g/l of acetylcholine (Ach) and noradrenaline (NA). In control group (rats with intact nerves) applications of Ach intensified inflammatory reaction and negatively affected the state of regenerating skin tissues: the effect of NA consists in promoting fibroblastic and leukocytic reactions. Simultaneous crushing of right sciatic nerve and infliction of the wound amplified the pathologic reaction in the wounds of denervated rats as compared to that in animals who did not undergo denervation, leading to rapid ulceration. NA administration caused negative consequences in wounds both in right and left sides. Crushing of the nerve was performed 7 days prior to wound infliction and on day 7 of the study of neurodystrophic processes has shown that Ach influence on denervated and non denervated wounds was positive, while NA influence was negative. After reinnervation adreno- and cholinoreactivity of granulation tissue was partially normalized both on the right and left sides.

Acetylcholine↗

Periaortic denervation in reconstructive surgery of coronary vessels.

Stimulation of sympathetic nervous conductive pathways and ganglia innervating the heart leads to a sudden increase in the cardiac performance and to a qualitative change in the phasic blood flow within the coronary vascular bed. This so-called malignant increase in the blood flow is accompanied by relative coronary insufficiency and increased mechanical stress imposed upon the coronary arteries. A denervation operation according to Arnulf does not prevent the propagation of excitation from the right stellate ganglion to the heart. A complete denervation is obtained by additional cutting of the right-side postganglional fibres. Then in a dog no changes occur in the coronary arterial blood flow measured at rest during the operation. In reconstructive surgery of coronary vessels in man, after denervation the peroperative blood flow in the aortocoronary bypass to the anterior interventicular branch increases. After a surgical denervation operation, the prevention of propagation of sudden neurogenic stimuli via the cervical sympathetic segment to the heart ventricles is the most striking result. Such a "protection" of the heart might retard the development rate of coronary insufficiency accompanying the ischaemic heart disease.

Animals↗

[Embryonic motoneurons transplanted into denervated skeletal muscles].

OBJECTIVE: To observe the living situation of homografting embryonic motoneurons in denervated skeletal muscles. METHODS: We transplanted dissociated ventral spinal cord cells from 12 embryonic days rats prelabeled with 5-bromo-2-deoxyuridine(Brdur) into denervated skeletal muscles of adult rats. The denervated skeletal muscles were collected at 9 and 22 weeks respectively, and Nissl, acetylcholinesterases immunocytochemistry and ATPase staining were used to show the transplanted embryonic motoneurons and the morphography of muscle fibers. RESULTS: Transplanted embryonic motoneurons could survive, extend out long axons, and form neuromuscular junctions with muscle fibers. Type grouping fibers with bigger transverse area were also observed in the experimental group. Muscle fibers were much smaller and did not form fiber type grouping in the control group. CONCLUSION: Homografting embryonic motoneurons could survive well and reinnervate the denervated skeletal muscles.

Animals↗

[Observation on the degeneration and regeneration of the Meissner's corpuscles in the monkey's denervated fingers following sensory nerve implantation under electron microscope].

OBJECTIVE: To observe the degeneration and regeneration of the Meissner's corpuscles after implanted sensory nerve into the denervated monkey's fingers under electron microscope. METHODS: The two finger nerves of the monkey's fingers were denervated. Afterwards, one finger nerve was cut off, and the other was reimplanted into the denervated finger. After 1, 3, 5, 8 and 12 months, the finger skin was cut off and observed under electron microscope. RESULTS: The degenerative changes of nerve ending in Meissner's corpuscles were observed after 1 month of denervation, and the basic structure of the corpuscles had no obvious changes. After 3 months, the axons of corpuscles were disappeared, and the volume of corpuscles was shrunk. The basic structure of nerves was disappeared, and the lemmocyte and neurolemma plate were changed after 5 months. The collagen fibrils in the corpuscles were gradually increased in 8 months, the endoneurial structure and interneurial matrix were completely disappeared and replaced by collagen fibrils in 12 months. After 3 months of nerve implantation, unmyelinated nerve fibers were appeared and grew into the corpuscles. A part of corpuscles innervated in 5 months. Most of corpuscles innervated and myelinated nerve fibers were observed in 8 months. And in 12 months, corpuscles innervated to normal level. CONCLUSION: The implantative sensory nerve by means of reinnervating the original corpuscles and regenerating new corpuscles could innervate the degenerative Meissner's corpuscles.

Animals↗

Increased fat degradation in the denervated muscle of frog.

The total lipids triglycerides, free fatty acids, glycerol and acetoaectate levels in the gastrocnemius muscle of frog denervated for 1 month were compared. A significant atrophy without any change in total DNA content per whole muscle was noted on denervation. No significant change in the mitochondrial protein content in the atrophied muscle was noted. Relative to total muscle mass, the total fat, triglyceride, free fatty acids and glycerols decreased on denervation. This suggests the increased degradation of fat during denervation. Concomittantly lypolytic and esterase activities in the atrophied muscle increased. Palmitate and pyruvate oxidations in the mitochondria of atrophied muscle and also the enzymes of beta-oxidative scheme increased. 14C-acetate incorporation rates revealed that there is a decrease in fatty acid synthesis in the atrophied muscle. It was suggested that the increased fatty acid oxidation and decreased fatty acid synthesis in the atrophic process may not be the result of a simple functional demand; but may involve more factors in terms of neuro-muscular functions.

Acetates↗

Effects of simultaneous denervation and tenotomy on the ultrastructure of a rat slow twitch muscle.

Simultaneous denervation and tenotomy causes atrophy of rat slow twitch soleus muscle. Apparently, the alterations are similar to those seen in denervated or tenotomized slow muscle. However, the extent of disorganization of myofibrils appears lower than that expected after a moderate period of time in only denervated or tenotomized muscle. This study indicates that after an initial proliferation of lysosomes, alterations of sarcotubular system and mitochondria proceed. Nevertheless, 45 days after denervation and tenotomy many mitochondria have a normal aspect.

Animals↗

Independence of changes in contraction properties and myofibrillar ATPase activity of denervated mammalian muscle on length of nerve stump.

1. Contractile properties of the fast extensor digitorum longus of one-month-old rats and of the fast peroneus longus muscles of adult rabbits were studied in vitro at 36 degrees C after nerve section close to the muscle. Changes in contraction properties (prolongation) are not observed until 48 hours after denervation in the rat and 14-30 days in the rabbit. 2. At no period after denervation are differences in twitch isometric contraction properties dependent on the length of the sectioned nerve stump. This lack of dependence of contractile behavior after denervation is in contrast to many metabolic changes which show a clear dependence on the length of the nerve stump. 3. It is concluded that the onset of denervation changes in contractile behavior are related to the loss of nerve-impulse activity, while the transient early metabolic changes are related to changes of fast axoplasmic flow, initiated after nerve section and therefore dependent on length of sectioned nerve stump.

Adenosine Triphosphatases↗

[Continuous distribution of ventilation-perfusion ratios following lung denervation in dogs by means of inert gas elimination method].

Pulmonary branches of the vagus nerve and sympathetic nerve-chain are severed frequently in thoracic surgery. In this investigation, respiratory function, this transection influence on, was studied, experimentally. Then, denervation of the left lung carried out in mongrel dogs. And distribution of ventilation-perfusion ratio actually present in the lung was measured by multiple inert gases elimination method. In dogs with denervated one side lungs, imbalance of distribution of ventilation-perfusion ratio existed, and it mean that there were areas of high VA/Q in distribution of ventilation. However, there was still no shunt and distribution of blood flow was no dispersion. From the it seems reasonable to infer that blood flow in pulmonary vessel diminished by pulmonary denervation. But arterial blood gas analysis showed normal degree. Accordingly pulmonary gas exchange should not be disturbed to high degree by imbalance of VA/Q distribution due to the denervation.

Animals↗

[Calcium transport and ATPase activity of sarcoplasmic reticulum in normal and denervated rabbit muscles].

The properties of sarcomplasmic reticulum Ca-pump from normal and denervated rabbit muscles were investigated. Ca+2 ion transport in denervated muscle reticulum was subject to Michaelis-Menten kinetics. The rate of fast Ca2+ outflux from the vesicles was enhanced after denervation; this caused a decrease in the transport efficiency and an increase of the "basic" ATP-ase. At the same time the rate of Ca2+ accumulation and the Ca-ATP-ase transport activity were enhances by a factor of 1.5. Kinetic properties of the denervated sarcoplasmic reticulum proved to be closely related to the features of the excitation-contraction cycle in these muscles.

Adenosine Triphosphatases↗

Changes in nerve conduction and Pi/PCr ratio during denervation-reinnervation of the gastrocsoleus muscles of rats.

The purpose of this investigation was to study the changes in nerve conduction and phosphate metabolites of the gastrocsoleus muscles of rats during denervation-reinnervation. Sixteen male Sprague-Dawley rats underwent unilateral crush-denervation of the left sciatic nerves at the sciatic notch. Six rats were used for measurement of motor conduction latency and action potential amplitude of the gastrocsoleus muscle by stimulating the sciatic nerve at one, two and eight weeks after nerve crush. The other ten rats were designated for evaluation of the ratio of inorganic phosphorous (Pi) to phosphocreatine (PCr) by a 31P-phosphoenergetic spectrometer at two weeks and eight weeks after nerve crush. None of the sciatic nerves showed conduction to the gastrocsoleus at one or two weeks after nerve crush. At eight weeks postcrush, the motor conduction latency returned to within normal limits, whereas the action potential amplitude was only 55% of the normal. For the eight-week period of study, the Pi/PCr ratio of the normal control muscles ranged between 0.09 +/- 0.02 and 0.11 +/- 0.02 (mean +/- SD). The denervated muscles showed an increase of Pi/PCr ratio by 54% at two weeks postcrush, compared to the respective contralateral control sides. The ratios returned to the normal value by eight weeks postcrush. In summary, these data suggested that the metabolic recovery of the crush-denervated muscle followed the same pattern as the parameters of nerve conduction.

Animals↗

Ovarian morphology and hormonal profiles in gilts following surgical denervation at day 12 of the oestrous cycle - preliminary data.

To establish the role of the nervous system in the etiopathogenesis of ovarian cysts we studied ovarian morphology and hormonal profiles in gilts that had undergone bilateral surgical denervation at day 12 of the oestrous cycle. Blood samples were collected from day 13 of the first cycle until day 20 of the second studied cycle. On this day the number of follicles (6 to 10 mm in diameter) was lower (p < 0.01) in the denervated ovaries when compared to the control group. Denervation resulted in a dramatic reduction in the number of TH/D betaH- and/or NPY-IR nerve fibres, especially in the vicinity of the follicles. Furthermore, denervation lead to a decrease (p < 0.05-0.001) in plasma concentrations of P(4) (at day 15 and 16 of the first cycle and during the luteal phase of the second studied cycle) and LH and E(2) (mainly during the perioestrous period). These results suggest that sympathetic neurons supplying ovaries may participate in the follicular development and steroidogenesis in gilts.

Animals↗

[Study on early motor neurotrophism of denervated red and white muscles].

OBJECTIVE: To investigate the early change of brain-derived neurotrophic factor (BDNF) in denervated red and white muscles and the regeneration of nerves innervating the muscles and to discuss the effect of the target organs on regeneration of the injured nerves. METHODS: Forty Wistar rats were divided into 5 groups. The sciatic nerves in 4 groups were sheared to make the models of the denervated muscles and the other one as control group. The amount of BDNF in muscles was measured with immunohistochemistry 1 day, 3 days, 7 days and 14 days after injury. The models of the regeneration of the nerves were made in another 15 rats whose sciatic nerves were disconnected with forceps. The nerve conduction velocity and electromyogram were tested with neuroelectrophysiology 7 days and 14 days after injury. RESULTS: The expression of BDNF in soleus increased significantly on the 1st day, the 3rd day and the 7th day (P<0.01); the expression in gastrocnemius was lower, but there was no significant difference (P>0.05) on the 1st day, the 3rd day, the 7th day and the 14th day when compared with control group. After 14 days of injury in the nerves innervating GAS and SOL, the nerve conduction velocities and the amplitudes of wave M recovered to (36.60+/-7.40)% and (19.9+/-6.4)% of normal value, and (42.50+/-3.50)% and (13.7+/-4.0)% of normal value respectively; there were no significant differences between the two muscles (P>0.05). CONCLUSION: There is difference in BDNF amount between the denervated red and white muscles, but the recovery of the two kinds of the motor nerves is similar, and the neurotrophism of denervated muscles was determined by all kinds of neurotrophic factors.

Animals↗