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The effect of denervation on myosin isoform synthesis in rabbit slow-type and fast-type muscles during terminal differentiation. Denervation induces differentiation into slow-type muscles.

The soleus and gastrocnemius medialis of eight-day-old rabbits were denervated and the effects were examined after fifty-two days by biochemical, cytochemical and mechanical methods. The contralateral soleus exhibited the properties of slow-type muscle, namely a predominance of slow-type myosin isoforms and slow-type oxidative fibers, slow twitch and low maximal velocity for shortening. The contralateral gastrocnemius exhibited the properties of fast-type muscle, namely a predominance of fast-type myosin isoforms and fast-type non-oxidative fibers, fast twitch and high maximal velocity of shortening. Denervation of muscles caused the differentiation of the two muscles towards slow-type muscles. Both denervated soleus and gastrocnemius muscles exhibited a predominance of slow-type myosins (either the normal type, made up of slow heavy and light chains, or the hybrid type, made up of slow heavy and regulatory light chains and fast essential light chains), a predominance of slow-type fibers, and slow mechanical properties. Thus, innervation in rabbit appears to be a determining factor for differentiation into fast-type muscle, but it is not necessary for differentiation into slow-type muscle. This conclusion contradicts the findings of previous studies in rat and thus raises new questions concerning the role of nerves in controlling the expression of myosin isoforms and the differentiation of muscle fibers.

Animals↗

Experimental study of denervated rat muscle. Part II: The effects of electrical stimulation on the denervated rat muscles.

Electrical stimulation has been widely employed for the treatment of peripheral nerve lesion, however, its effects are not well known. Effects of electrical stimulation on denervated muscles were studied by measuring the weight of anterior crural muscles and the diameter of muscle fibers of the extensor digitorum longus muscle of the rat. The muscle fibers were classified by myofibrillar ATPase reaction. The denervated muscle showed loss of weight, a marked decrease in diameter of type 1 fibers and a small increase in diameter of type 2 fibers. Electrical stimulation suppressed weight loss of the denervated muscles. Electrical stimulation with high frequency cycle, like phasic motoneuron discharges, significantly suppressed the increase in diameter of type 2 muscle fibers. Electrical stimulation with low frequency cycle, like tonic motoneuron discharge, significantly suppressed the decrease in diameter of type 1 muscle fibers.

Adenosine Triphosphatases↗

Behavioral and biochemical evidence for a different effect of repeated administration of L-dopa and bromocriptine on denervated versus non-denervated striatal dopamine receptors.

The effect of repeated administration of bromocriptine and L-3,4-dihydroxyphenylalanine (L-DOPA) was studied behaviorally and biochemically in rats with a unilateral lesion of the nigrostriatal pathway. Groups of rats injected eight times with bromocriptine or L-DOPA significantly increased their contraversive circling. Rats receiving only two injections of bromocriptine did not. Animals receiving two injections of L-DOPA showed a slight but significant increase in circling. The affinity of the binding of [3H]spiperone to the dopamine receptors was unchanged by the lesion or the treatments, while the density of the binding was significantly modified. Chronic treatment with bromocriptine induced a significant decrease in the density of D2 dopamine receptors in the intact striata, while on the lesioned side, it remained unchanged. By contrast, chronic administration of L-DOPA induced a significant increase in density of the striatal dopamine receptors in the lesioned striata in addition to that caused by denervation, while the decrease on the intact side was not significant. It seems that contrary to the intact striatum, the lesioned side had a defective down-regulation mechanism in response to chronic treatment with a dopamine agonist. The results also show that L-DOPA was more potent than bromocriptine in inducing agonist supersensitivity in a denervated striatum. This may explain why chronic treatment with bromocriptine has a lesser tendency to induce dyskinesia in patients with Parkinson's disease.

Animals↗

Effects of complete renal denervation and selective afferent renal denervation on the hypertension induced by intrarenal norepinephrine infusion in conscious rats.

To test the hypothesis that continuous intrarenal norepinephrine (NE) infusions produce hypertension via activation of afferent renal nerves (ARN), rats were subjected to complete renal denervation (RN-x), selective renal deafferentation (ARN-x) or sham surgery, prior to infusion of NE. In the pre-infusion period, mean arterial pressure (MAP) was significantly lower in RN-x than in ARN-x or sham-operated rats. Plasma renin concentration (PRC) was significantly reduced following ARN-x, but not RN-x. During 5-day intrarenal infusions of 4, 12 or 36 micrograms NE/kg per h, MAP rose to similar levels in RN-x and sham-RN-x rats. However, RN-x rats exhibited significantly elevated PRC levels, suggesting that denervation supersensitivity masked the possible effects of RN-x. In sham-RN-x rats, MAP increased significantly more during intrarenal infusion of 12 micrograms NE/kg per h than during intravenous infusion of the same amount. In ARN-x rats, MAP rose to a similar degree during intravenous and intrarenal infusions. The pressor responses in the ARN-x rats, however, were not significantly smaller at any point than those in intact rats. PRC rose to comparable levels in ARN-x and intact rats. Thus, in normotensive rats, efferent renal nerves (ERN) but not ARN are of functional significance in maintaining basal blood pressure. ARN may be involved in the control of renin release. Since neither RN-x nor ARN-x attenuated the development of hypertension, renal nerves are not necessary for the full expression of hypertension in this model.

Afferent Pathways↗

Effects of denervation on the rate of entry of inorganic phosphate into rat slow and fast muscles: selective inhibition of denervation changes by actinomycin D.

Actinomycin D abolishes the post denervation increase in inorganic phosphate flow observed in the fast gastrocnemius muscle. In the slow soleus muscle, the initial decrease in phosphate flow is unaffected but the secondary rise is suppressed in the same manner as in the fast muscle. These observations put the post denervation increase in inorganic phosphate flow on a par with the development of extrajunctional cholinergic receptors in being the result of the synthesis of new proteins. It has the added advantage of being suitable to quantitative assessment at the whole muscle level.

Animals↗

Involvement of adenylate cyclase in mechanisms of denervation supersensitivity following surgical denervation of the dog heart.

Following surgical disruption (4-16 weeks) of the nerves supplying the dog heart, catecholamine (norepinephrine and epinephrine) levels in the atria and ventricles were markedly reduced. Using the 10,000 g particulate fraction as an enzyme source, the activation of adenylate cyclase by norepinephrine was considerably greater in the denervated myocardial preparations (atria and ventricles) than in control hearts. Moreover, in the denervated ventricular preparation fluoride (5 and 10mM) elicited a significantly greater stimulation of the enzyme than that observed in the controls.

Adenylyl Cyclases↗

[Acquired disorders of peritoneal cavity muscles. Abdominal wall denervation in pregnancy, denervation incontinence, and continent and incontinent constipation].

The peritoneal cavity has a fascial skeleton that is kept under tension by permanent variable resting tone maintained by the abdominal muscles. The lateral abdominal muscles, the diaphragm and the pelvic floor are all components of this fasciomuscular support system. Voluntary and reflective changes in muscle tension allow the entry and exit of matter into and out of the spherical abdominal cavity by opening and closing of specialized wall segments called sphincters. We have previously demonstrated the existence of a resting tone in the tail muscles of mammals from which the human pelvic floor muscles are derived. The pelvic floor and its integrated sphincters form the anorectal organ of continence. This organ is much weaker in females than in males. The spinal centers that govern continence, contain in the female significantly fewer ganglion cells than the corresponding centers in the male. Childbirth and a commonly found tendency to develop constipation are additional stressors for the congenitally weaker female organ of continence. We explain in this paper why the abdominal wall and the pelvic floor may suffer stretch-induced denervation injuries during pregnancy and delivery. Such damage may persist in later life and can give rise to incontinence and "flabby abdomen". Based on our work in this field, we found a new differentiation between continent and incontinent constipation. Continent constipation is caused by spasticity of the pelvic floor characterized by abnormally high sphincter activity. This spastic pelvic floor syndrome can be treated successfully by psychotherapeutic techniques. Incontinent constipation, in contrast, is always associated with subnormal activity of the sphincters and may be a cause of rectal prolapse. It can be treated successfully by anterior rectosigmoid resection. Incontinent constipation will also require operative approximation of the levators in many cases. Improvement cannot be expected to result from this procedure, however, unless the pelvic floor shows some residual resting activity.

Abdominal Muscles↗

Animal models of Alzheimer's disease: glutamatergic denervation as an alternative approach to cholinergic denervation.

Alzheimer's disease (AD) is a neurodegenerative disorder that severely reduces lifespan. In this article, a new, glutamatergic denervation model of AD is presented as a supplement to the well known cholinergic one, because these models are trying to mimic different aspects of the pathology in AD. Impaired memory and disorientation are prominent features in the symptomatology of AD. In searching for neurochemical systems associated with the initial cognitive disorders of AD, a reorientation from cholinergic to glutamatergic systems is suggested. Results from recent behavioral studies of damage to the temporal and entorhinal cortices in rats imply that these structures are strongly involved in mnemonic function. Findings from Alzheimer brains and laboratory animals indicate that major losses of glutamatergic receptors may underly the cognitive impairment seen in AD patients. A growing body of evidence appears to support a glutamatergic hypothesis of AD. Possible pharmacological approaches are suggested.

Alzheimer Disease↗

Outgrowth of cholinergic nerves in the rat urinary bladder either partially denervated or partially denervated and decentralized.

Unilateral excision of the pelvic ganglion caused a loss in the number of AChE-positive nerves in the rat urinary bladder both on the operated side and on the contralateral side, thus indicating a bilateral intramural distribution of cholinergic nerves derived from the pelvic nerve. In the course of the subsequent observation period (3-28 days) the AChE-positive nerves increased in number and in staining intensity and further, the nerves became ramified and twisted. Similar events were found to occur in the urinary bladder decentralized on one side and denervated on the other. The morphological findings indicate an outgrowth of cholinergic nerves by collateral sprouting. These findings are discussed in relation to previous physiological studies.

Acetylcholinesterase↗

Denervated muscle flaps: mass and thickness changes following denervation.

It has been previously well documented in different animal models and different muscle groups that there is an early rapid loss, followed by stabilization, of muscle mass. This study supports the findings and, in addition, correlates the change in thickness with the change in weight after ligation of the thoracodorsal pedicle.

Animals↗