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PubMed1983

Extensive dendritic sprouting induced by close axotomy of central neurons in the lamprey.

Massive dendritic sprouting was induced in identified giant reticulospinal neurons of the lamprey by axotomy close to the soma. An axonal lesion slightly farther from the cell body induced new growth from both dendrites and axon. The amount of new growth per cell was the same whether it originated from the dendrites alone or from axonal and dendritic compartments. The location of the axonal lesion therefore determines where, in the neuron, membrane is inserted to produce the new neurites. The dendritic tree of a differentiated vertebrate central neuron was shown to have sufficient plasticity to extend new growth for several millimeters beyond the normal dendritic domain.

Animals↗
PubMed1994

Changes in retrogradely labelled neurones in the red nucleus and cortex after depletion of motoneurones by axotomy in neonatal rats.

Following nerve injury to the sciatic nerve in neonatal rats many motoneurones die, so that the target of the rubrospinal and corticospinal cord is altered. Retrograde labelling of neurones terminating in this region shows that, in the red nucleus as well as cerebral cortex, there is a significant reduction in labelled neurones on the side contralateral to the nerve injury. Thus neurones in the brain that give rise to descending fibres are influenced by the altered environment in the spinal cord following axotomy at birth.

Animals↗
PubMed1978

Molecular forms of acetylcholinesterase in the ciliary ganglion and iris of the chick. Developmental changes and effects of axotomy.

Four molecular forms of acetylcholinesterase (AChE) have been observed in extracts from ciliary ganglion and iris by gel electrophoresis followed by Koelle's reaction and densitometry on gels. Forms I, II, and III (order of anodic migration) are present in the 'soluble fraction' (SF) while forms II, III, and IV appear in the 'membranous fraction' (MF). 10 days after postganglionic axotomy in young chickens, the relative proportions of the membranous forms were changed in both the ciliary ganglion and iris, with a marked reduction of form IV occurring. A characteristic evolution of both the soluble and membranous forms of AChE was evident through different developmental stages (10th day of incubation; 2nd, 11th and 56th day posthatching). In the ciliary ganglion the faster components were reduced in favor of form IV. Conversely, the relative proportion of the faster components was increased in the iris. The observed changes in the AChE forms are compared with changes in the structure and function of these organs known to occur in the conditions under study. Evidence is presented which suggests a junctional localization for the form IV in both the ciliary ganglion and iris.

Acetylcholinesterase↗
PubMed1990

Administration of testosterone fails to attenuate axotomy-induced motoneuron loss but results in castration-like effect in young male rats.

It was shown previously that the severity of motoneuron loss induced by nerve transection in rats 3 or 6 weeks of age was correlated inversely with the level of testosterone in circulation [Yu, W.H.A., Exp. Neurol. 102: 230-235, 1988], and that administration of testosterone to female rats attenuated axotomy-induced neuronal cell loss in a dose-dependent manner [Yu, W.H.A., J. Neurosci. 9: 3908-3914, 1989]. The present study was undertaken to examine whether elevation of the level of plasma testosterone in gonadally intact male rats by exogenous testosterone would likewise reduce neuronal cell loss. Following unilateral transection of the hypoglossal and facial nerve at 3 or 6 weeks after birth, rats received subcutaneous injections of 0.5, 1.0, or 2.0 mg testosterone propionate (TP) dissolved in 0.1 ml sesame oil or an equal volume of vehicle alone twice weekly for the first 4 postaxotomy weeks, and once weekly thereafter for additional 6 weeks. Results indicated that males axotomized at 3 weeks of age and treated with 1.0 or 2.0 mg TP had nearly twofold greater neuronal cell loss than oil-treated controls. The resultant cell loss was similar to that of castrated males or females without TP treatment despite the fact that TP treatment significantly elevated the plasma testosterone level. Neuronal cell loss in males axotomized at 6 weeks of age, however, was unaffected by TP treatment. Although testicular atrophy was noted in all TP-treated rats, the damage appeared to be greater in the testis of the 3-week-old than that of 6-week-old rats, as manifested by the castration-like effect of neuronal cell loss in prepubertal rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1987

Structural changes in intercostal motoneurones following axotomy.

Motoneurone disease (MND or amyotrophic lateral sclerosis) is a paralysing disease of unknown cause involving progressive, widespread muscle atrophy due to degeneration of spinal and other motoneurones and an accompanying loss of Betz cells in the motor cortex. A current hypothesis attributes the disease to the loss of a muscle-derived neurotrophic factor acting in concert with the normal age-related deterioration and loss of motoneurones. The roots of this hypothesis are traced through research based mainly on the developing neuromuscular system, and in particular on the age-related processes of natural motoneurone death during embryogenesis: the neonatal reduction of polyneuronal innervation and the age-dependent variations in motor nerve terminal sprouting in response to partial denervation. A consideration of the disease process itself in association with the review of earlier work provide the background for the present work which reexamines ultrastructurally the chromatolytic and later responses to axotomy and the muscle-dependent factors responsible for the reformation of the Nissl bodies.

Animals↗
PubMed1980

A reliable method for demonstrating axonal degeneration shortly after axotomy.

A method has been elaborated by which degenerating axons can be selectively impregnated with silver. Based on reconsideration of the physicochemical mechanisms of the degeneration methods it takes advantage of physical developers over the chemical ones. The staining procedure is applied to frozen sections of brains fixed with formol. It consists of 6 steps: (1) pretreatment with alkaline hydroxylamine, (2) washing in acetic acid, (3) impregnation in silver nitrate in the presence of ferric ions, (4) washing in citric acid, (5) physical development, and (6) washing in acetic acid. By electron microscopy silver precipitates by this method are almost entirely restricted to the cytoplasm of dense, degenerating axons, sparing mitochondria and myelin sheaths. No special expertise is required to achieve reproducible results. Large numbers of sections treated simultaneously, and large sections, can be stained uniformly. Light microscopic criteria are described which help diagnose the source of possible failures. Low background staining allows dark field illumination and television image analysis to be applied. The method works at survival times of only 3 to 5 days after axotomy. Hence, degenerating axons and axon terminals can be stained in alternating sections from the same brain using this method and another being described separately, which, using different conditions, demonstrates degenerating axon terminals.

Animals↗
PubMed2001

[Effects of different methods of fetal spinal cord tissue transplanted on reversing the axotomy-induced neurons atrophy rats injured spinal cord].

OBJECTIVE: To explore the effects of different methods of fetal spinal cord(FSC) tissue transplanted on reversing the axotomy-induced neurons atrophy of adult rats injured spinal cord. METHODS: One hundred and twenty adult rats received lumbar spinal cord hemisection. Experimental rats were divided into five groups, the control group(Group A); spinal cord hemisection only(Group B); spinal cord hemisection plus FSC transplant (Group C); spinal cord hemisection plus FSC transplant plus pedicled paraspinal muscle(Group D); spinal cord hemisection plus FSC transplant plus pedicled omentum (Group E). Combined behavioral scores(CBS), somatosensory evoked potentials (SEP), motor evoked potentials(MEP) were examined to evaluate the recovery of neurological function after operation. Rats were sacrificed after 1, 4 and 12 weeks. Nissl stained section was used for neurons quantitative image analysis. The positive cells were quantitative analysis by computer image analysis system. RESULTS: The different methods of FSC tissue transplantation could prevent the neurons atrophy secondary to axon injury of spinal cord in adult rats. The size of neurons were observed in five groups, they were group E > group D > group C > group B > group A (P < 0.05). Those increases in size of neurons were paralleled with a significant improvement in neurological function recovery. CONCLUSION: It indicates that the different methods of FSC tissue transplantation can maintain the neurons morphology and improve the neurological function of rats.

Animals↗
PubMed1992

Microtubule-based filopodium-like protrusions form after axotomy.

The growth cone at the front of a growing neurite often has F-actin-rich structures--digitate filopodia and sheet-like veils and lamellipodia--whose protrusion advances the leading edge. Microtubules and other cytoplasmic constituents later fill the protruded area, transforming it into new neuritic length. Growth can be initiated from an axon by transecting it. We have used video-enhanced contrast-differential interference contrast microscopy to observe the early events following transection of Aplysia axons in culture. Many filopodium-like protrusions (FLPs) grew rapidly (average instantaneous velocity of 1.6 microns/sec) from the sides and end of the axon stump within minutes of transection. Some of these displayed bidirectional transport of swellings, at a rate similar to fast axonal transport. Dihydrocytochalasin B, which blocks actin polymerization, only halved the number of FLPs that formed within 10 min of transection, and actually increased the number of transporting FLPs. Nocodazole, a microtubule-specific drug, also halved the number of FLPs, but none of them displayed transport of swellings. No FLPs formed in the presence of both drugs. In transected axons that had not been exposed to either drug, removal of the plasma membrane revealed fibers in many of the FLPs; immunofluorescence showed these fibers to be microtubules. Thus, a substantial number of the FLPs that form soon after axotomy are microtubule based, rather than actin based, underscoring the potential of microtubules to drive the rapid extension of neuritic precursors.

Actins↗
PubMed1990

[Ganglionic synapses and synaptic transmission after axotomy of sympathetic neurons in the frog].

In frog ganglia, efficacy of synaptic transmission was analyzed in parallel with the number of synapses at different times after axotomy of sympathetic neurons: the number of synapses was at their minimum at two weeks whereas depression of synaptic transmission was strongest at one month. The relationship between the presence of synaptic dense specializations and the existence of efficacious transmission is discussed.

Animals↗
PubMed1986

Consequences of partial axotomy for production of neurotransmitter vesicles and routing of rapidly transported membrane glycoproteins in the axonal tree.

It was found previously that transection of one branch of the bifurcate axon of a giant serotonergic neuron of Aplysia causes a proportionate decrease in the export of transmitter storage vesicles from the cell body, despite the ability of the remaining branch to transport all of the vesicles normally exported (Aletta and Goldberg, 1982). We report here evidence that this down-regulation is achieved by a decrease in the production of vesicles, rather than a slowing of the processing of vesicles for export from the cell body. Counts of serotonergic vesicles in the cell body show that the size of the somal pool of vesicles is not increased at a time when their rate of export has been halved. Also, transection of one or both branches of the axon decreases the amount of 3H-fucose incorporated during a short period into a putative vesicle membrane glycoprotein but not into other glycoproteins. The results indicate that axotomy should be a useful technique for studying the mechanism of regulation of the synthesis of a secretory organelle. It was also previously shown that transection of one branch of the axon far from the cell body does not impair the ability of the injured branch to transport serotonergic vesicles, yet the majority of vesicles that would normally enter that branch are nevertheless rerouted into the uninjured branch. We have studied quantitatively the partitioning between the 2 branches, after one has been transected distally, of 6 fucosyl glycoproteins, including the putative vesicle glycoprotein and a glycoprotein whose transport moderately increases after transection.(ABSTRACT TRUNCATED AT 250 WORDS)

Aplysia↗
PubMed1988

Changes in cytoskeletal proteins in the rat facial nucleus following axotomy.

Changes in L-35S-methionine incorporation into cytoskeletal proteins of the facial nucleus of the rat were studied at various times after unilateral crush or resection of the facial nerve by using 2-dimensional gel electrophoresis and fluorography. We found an increase in labeling of actin and tubulin and a decrease in the 68 kDa and 150 kDa neurofilament polypeptides (200 kDa was not studied). The increase in actin and decrease in neurofilament polypeptide labeling was already significant by 24 hr after nerve resection. These changes were more pronounced after nerve resection than after nerve crush on day 7; actin labeling increased to 270%, and tubulin to 205% of contralateral normal nuclei after resection, whereas both proteins increased to only 165% after crush. Neurofilament labeling decreased to 28% of the contralateral side after resection and to 50% after crush. Immunocytochemistry with a monoclonal antibody to the 150 kDa neurofilament component revealed decreased immunoreactivity in the axotomized facial axons at the inner facial genu, 1 cm proximal to the crush. In contrast, neurofilament immunoreactivity was not decreased in the axotomized perikarya of the facial motoneurons. All changes returned to normal 3 weeks after crush. When axonal regeneration was impeded by nerve resection, incorporation into tubulin remained elevated and into neurofilament proteins remained depressed. Actin returned to normal after either nerve resection or crush. We conclude that the synthesis of tubulin and neurofilament proteins following axotomy is regulated by successful axonal regeneration and/or target contact. Actin synthesis seems to be regulated independently of target-derived factors.

Actins↗
PubMedDate not supplied

Distribution of degeneration of cholinergic neurons in the septum following axotomy in different portions of the fimbria-fornix: a correlation between degree of cell loss and proximity of neuronal somata to the lesion.

The degree of cell loss of immunohistochemically stained cholinergic neurons was quantitatively compared in equivalent regions of the septum in three groups of animals with lesions transecting their axons at different levels in the fimbria-fornix (FF). Locations of different septal regions and of FF lesions were defined according to their distances from fixed anatomical reference points. Individual animals all exhibited a gradient of cholinergic cell loss, such that the severity of cell loss diminished progressively in the rostral and ventral directions as the distance from the lesion increased beyond a certain point. Comparison of animals with FF lesions in different locations showed that this gradient of cell loss shifts in the caudo-rostral and dorso-ventral directions within the septal complex in direct relation to the proximity of the axotomizing FF lesion. These findings suggest that among septal cholinergic neurons there is a fixed spatial relationship between the distance of neuronal somata from an axotomizing FF lesion and the likelihood of neuronal loss in response to axotomy. This relationship could not be defined precisely using the material studied, but simple geometrical calculations showed that within 2500 microns of the lesion cell loss is always pronounced (less than 30 per cent detectable cells vs controls) and beyond 4000 microns cell loss is generally not severe (greater than 80 per cent detectable cells). Between these two distances cell loss diminishes in a gradiated manner. Thus, relatively small differences (1 mm) in the location of FF lesions can lead to marked differences in the severity of degeneration observed in certain equivalent regions of the septum. The findings have implications both for attempts to understand the causes underlying retrograde neuronal degeneration and for studies investigating means of preventing retrograde degeneration of cholinergic septal neurons.

Animals↗
PubMed1987

Changes in the dendritic geometry of mouse superior cervical ganglion cells following postganglionic axotomy.

The dendritic geometry of mouse superior cervical ganglion cells was studied over periods of up to 3 months after postganglionic axotomy. Intracellular injection of HRP showed that total dendritic length and complexity were reduced by 60-70%, on average, among cells whose postganglionic axons had been crushed 2 weeks before. Both parameters gradually recovered in parallel with ganglion cell reinnervation of the periphery. These results indicate that neuronal interactions with peripheral targets influence the configuration of ganglion cell dendrites throughout life. The implications of this conclusion are discussed.

Animals↗
PubMed1985

[Effects of axotomy on the activity of the motor neurons of the external ocular motor nucleus during saccadic movements].

The instantaneous firing frequency of cat abducens nucleus motoneurons (Mns) during spontaneous saccadic eye movements has been analyzed. Recordings were carried out from both control and axotomized Mns. Firing frequency of control Mns increased gradually during the first four to five interspike intervals, at which point maximum firing frequency was reached. Axotomized Mns showed an increase in firing frequency only up to the second or third interval, decreasing rapidly then. Linear relationships, with high correlation coefficients, were established between the first five intervals versus maximum frequency or peak eye velocity during saccades, in both control and axotomized Mns. However, the latter showed a decrease in the linear correlation from the third interval because of the decrease in the slope of the relationship. Functional implications of these results are discussed according to the present hypothesis on the effects of axotomy upon oculomotor neurons.

Abducens Nerve↗
PubMed1977

Light and electron microscopic studies on the intrinsic innervation of the guinea-pig seminal vesicle following selective axotomy.

Selected peripheral autonomic nerves have been surgically divided or removed and the seminal vesicles subsequently examined using neurohistochemical and electron microscopic techniques. Following bilateral hypogastric anf pelvic nerve transection, the arrangement and distribution of intramural axons 14 days after operation were similar to those in control specimens. In contrast, removal of the pelvic plexus was accompanied by a gradual reduction of catecholamine and acetylcholinesterase so that by the seventh post-operative day nerves were not observed light microscopically in the muscle coat or the submucosa. These observations have been endorsed using electron microscopy, and the fine structure of intramural autonomic nerves in response to axotomy has been monitored during the post-operative period. It has been concluded that the cell bodies of axons which supply the wall of the seminal vesicles are located within the pelvic plexus and do not extend proximal to the sites of division of the hypogastric and pelvic nerves.

Acetylcholinesterase↗
PubMed1977

[Dynamics, following axotomy, of the A1 and A2 median protocerebral neurosecretory cells of the African locust. I. Histophysiological study].

In the African locust, the secretory dynamics of the A1 and A2 median protocerebral neurosecretory cells (M-NSC) is evaluated by the product content and the gonadotropic action of these cells. The axotomy of the A1 and A2 M-NSC disturbes their secretory dynamics. The axonal regeneration, if it leads to a reconnexion with the corpora cardiaca (CC), restores a normal secretory dynamics of the M-NSC. Without reconnexion to the CC, the nervi corpori cardiaci interni (NCCI) do note regenerate or regenerate to form new nerve endings. In these cases, the secretory dynamics of the M-NSC remains more or less inhibited specially that of the A2 M-NSC which can be completely suppressed. A functional state of the A2 M-NSC could be necessary for the beginning of the vitellogenesis. In the CC, separated from the regenerating M-NSC, the A1 and A2 neurosecretory products are transformed into large globules which became intensively basophil before disappearance.

Animals↗
PubMed1984

Stimulation of protein synthesis and glucose utilization in the hypoglossal nucleus induced by axotomy.

The metabolic responses of rat hypoglossal nuclei to unilateral section of the 12th cranial nerve have been studied. Changes in the rates of protein synthesis and glucose utilization in the regenerating nucleus were determined with two quantitative autoradiographic techniques, the L-[1-14C]leucine method and the [14C] deoxyglucose method, respectively. The results show that both of these processes increase in the nucleus ipsilateral to the sectioned nerve and are unaffected in the contralateral nucleus as compared with sham-operated animals. The time courses of these metabolic changes have been compared with that of the return of functional innervation of the tongue. An increase in glucose utilization is first detected 24 hr postaxotomy. It is maximal between 1 and 3 days postaxotomy and constitutes an 84% increase over the rate in the contralateral control nucleus. The increase in protein synthesis is of smaller magnitude than that of glucose utilization. It is maximal at 48 hr after axotomy and constitutes a 25% increase over the rate in the contralateral nucleus. The increases in both of these metabolic processes persist even after functional recovery of the tongue at 21 days postaxotomy. Protein synthesis and glucose utilization return to normal levels between 24 and 35 days postaxotomy. Although the time courses of the changes in protein synthesis and glucose utilization are similar, the magnitude of the increase in glucose utilization is too large to be accounted for by the energy requirements of the relatively small increase in protein synthesis and probably reflects other processes as well, including altered function of the soma-dendritic membrane of regenerating neurons.

Animals↗
PubMed1995

A novel RING-H2 motif protein downregulated by axotomy: its characteristic localization at the postsynaptic density of axosomatic synapse.

Axonal injury and its repair are common and basic neuropathological processes in the CNS, and are composed of a complex of events in a molecular term. In order to get a comprehensive understanding of these processes, we isolated several known and unknown genes which were up-or downregulated in the facial nucleus after transection of the facial nerve by a subtractive/differential screening. Among them, we focus on one downregulated gene, named Neurodap1, because this gene encodes a novel protein carrying the RING-H2 sequence motif categorized in the zinc finger family. Immunoelectron microscopic analysis revealed that the protein encoded by Neurodap1, Neurodap1, was distributed mainly on the cytoplasmic side of the membranes constituting endoplasmic reticulum and Golgi apparatus, supporting the notion of a previously postulated function of RING-H2 motif proteins, that is, involvement in the protein sorting machinery. More interestingly, Neurodap1 was also bound to the postsynaptic density (PSD) region of axosomatic synapses. This fact suggests that Neurodap1 is associated with a specific system sorting proteins to PSD. Therefore, Neurodap1, a newly identified protein as an axotomy-suppressed gene product, might play a significant role in synaptic communication and plasticity through the control of the formation of PSD for maintaining vital functions of nerve cells.

Amino Acid Sequence↗