Norepinephrine and serotonin axonal dynamics and clinical depression: a commentary on the interaction between serotonergic and noradrenergic axons during axonal regeneration.
Explore the source record for details and available documents.
Animals↗
SEARCH · Search PubMed
Results for “Axons”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Further studies on the nature of the excitable system in nerve. I. Voltage-induced axoplasm movement in squid axons. II. Penetration of surviving, excitable axons by proteases. III. Effects of proteases and of phospholipases on lobster giant axon resistance and capacity.
Explore the source record for details and available documents.
Animals↗
Altered axons and axon terminals in the lateral vestibular nucleus of the rat. Possible example of axonal remodeling.
Explore the source record for details and available documents.
Acid Phosphatase↗
Model of spike propagation reliability along the myelinated axon corrupted by axonal intrinsic noise sources.
We investigated how selected electromorphological parameters of myelinated axons influence the preservation of interspike intervals when the propagation of action potentials is corrupted by axonal intrinsic noise. Hereby we tried to determine how the intrinsic axonal noise influences the performance of axons serving as carriers for temporal coding. The strategy of this coding supposes that interspike intervals presented to higher order neurons would minimally be deprived of information included in interspike intervals at the axonal initial segment. Our experiments were conducted using a computer model of the myelinated axon constructed in a software environment GENESIS (GEneral NEural SImulation System). We varied the axonal diameter, myelin sheath thickness, axonal length, stimulation current and channel distribution to determine how these parameters influence the role of noise in spike propagation and hence in preserving the interspike intervals. Our results, expressed as the standard deviation of spike travel times, showed that by stimulating the axons with regular rectangular pulses the interspike intervals were preserved with a microsecond accuracy. Stimulation with pulses imitating postsynaptic currents, greater changes of interspike intervals were found, but the influence of implemented noise on the jitter of interspike intervals was approximately the same.
Action Potentials↗
The predominant form in which neurofilament subunits undergo axonal transport varies during axonal initiation, elongation, and maturation.
The forms in which neurofilament (NF) subunits undergo axonal transport is controversial. Recent studies from have provided real-time visualization of the slow axonal transport of NF subunits by transfecting neuronal cultures with constructs encoding green fluorescent protein (GFP)-conjugated NF-M subunits. In our studies in differentiated NB2a/d1 cells, the majority NF subunits underwent transport in the form of punctate NF precursors, while studies in cultured neurons have demonstrated transport of NF subunits in predominantly filamentous form. Although different constructs were used in these studies, transfection of the same cultured neurons with our construct yielded the filamentous pattern observed by others, while transfection of our cultures with their construct generated punctate structures, confirming that the observed differences did not reflect variances in assembly-competence among the constructs. Manipulation of intracellular kinase, phosphatase, and protease activities shifted the predominant form of GFP-conjugated subunits between punctate and filamentous, confirming, as shown previously for vimentin, that punctate structures represent precursors for intermediate filament formation. Since these prior studies were conducted at markedly differing neuronal differentiation states, we tested the alternate hypothesis that these differing results reflected developmental alterations in NF dynamics that accompany various stages of neuritogenesis. We conducted time-course analyses of transfected NB2a/d1 cells, including monitoring of transfected cells over several days, as well as transfecting cells at varying intervals prior to and following induction of differentiation and axonal neurite outgrowth. GFP-conjugated subunits were predominantly filamentous during the period of most robust axonal outgrowth and NF accumulation, and presented a mixed profile of punctate and filamentous forms prior to neuritogenesis and following the developmental slowing of neurite outgrowth. These analyses demonstrate that NF subunits are capable of undergoing axonal transport in multiple forms, and that the predominant form in which NF subunits undergo axonal transport varies in accord with the rate of axonal elongation and accumulation of NFs within developing axons.
Animals↗
Axonal regeneration in wobbler motor neuron disease: quantitative histologic and axonal transport studies.
The regenerative capacity of the cervical anterior horn cells was studied at 4 and 7 days following forelimb nerve crush in 19 wobbler mice and 18 normal littermates. Quantitative histologic and radiolabeled axonal transport techniques showed that the axotomized neurons of the wobbler mouse supported active axonal elongation. However, the average axon outgrowth rate determined by histologic technique was diminished by 25% and the fastest axon outgrowth rate determined by axonal transport technique was also decreased by 30% in wobbler mice as compared to controls. The distal labeled peak was absent in the wobbler mouse at 7 days, indicating that the regeneration rate of individual axons was widely dispersed. Histologic studies also showed that the wobbler axons grew slowly. This study suggests that axonal regeneration does occur in motor neurons undergoing a primary neuronopathy. However, the regenerative capacity was reduced and this appears to reflect an impairment of functional integrity in the anterior horn cells of the wobbler mouse.
Animals↗
Depression of fast axonal transport in axons demyelinated by intraneural injection of a neurotoxin from K. humboldtiana.
Tullidinol, a neurotoxin extracted from the Karwinskia humboldtiana fruit, dissolved in peanut oil was injected into the right sciatic nerve of adult cats. The contralateral sciatic nerve received an equivalent volume of peanut oil alone. The fast axonal transport of labeled ([3H]Leucine) protein was studied in sensory and motor axons of both sciatic nerves. The radioactive label was pressure injected either into the L7 dorsal root ganglion or the ventral region of the same spinal cord segment. Several days after the toxin injection, the cat limped and the Achilles tendon reflex was nearly absent in the right hind limb. The amount of transported label was decreased distal to the site of toxin injection. Proximal to this site, the transported material was damned. Sensory and motor axons showed similar changes. In addition, the toxin produced demyelination and axonal degeneration. Axonal transport and the structure of the axons were normal in the contralateral nerve. Both, Schwann cells and axons of the right sciatic nerve showed globular inclusions, presumably oil droplets containing the toxin. We conclude that Schwann cells and axons as well are tullidinol targets.
Achilles Tendon↗
Focal axonal injury: the early axonal response to stretch.
The development of a model for axonal injury in the optic nerve of the guinea pig has allowed analysis of early morphological changes within damaged axons. We provide evidence that the initial site of damage after stretch is the nodes of Ranvier, some of which develop 'nodal blebs'. The development of nodel blebs is correlated with the loss of subaxolemmal density, disruption of the neurofilament cytoskeleton and aggregation of membranous profiles of smooth endoplasmic reticulum. Nodal blebs are numerous 15 min after injury but less so at later survivals. The glial-axonal junction is intact at early survivals in damaged nodes. Marked accumulation of membranous organelles occurs in the paranodal and internodal regions adjacent to damaged nodes between two and six hours and is correlated with disruption of the myelin sheath. Axotomy and the formation of degeneration bulbs occurs between 24 and 72 h. The area of axonal injury is invaded by phagocytic cells by 72 h and large numbers of myelin figures occur within the neuropil until 14 days. The results are compared with those of other studies of diffuse axonal injury and other neuropathies. The time course of axonal changes is more rapid than during Wallerian degeneration. Our data from longer surviving animals is exactly comparable with published data. We are confident that the principal site of axonal injury is the node of Ranvier. We suggest that damage at the node results in disruption of axonal transport, which in turn leads to a cascade of events, culminating in axotomy between 24 and 72 h after the initial insult.
Animals↗
The smooth endoplasmic reticulum: structure and role in the renewal of axonal membrane and synaptic vesicles by fast axonal transport.
The spatial arrangement of the smooth endoplasmic reticulum (SER) was studied in 0.5-2 mum thick sections of rat spinal and chick ciliary ganglia previously impregnated with heavy metal salts. Electron microscopy at low (10-5 V) or high (10-6 V) voltage showed the impregnated SER as a continuous system extending probably from the perikaryon to the axon terminal. Tubules of the SER, which were running in a parallel direction with the axon, were occasionally seen in close apposition with the axonal membrane. Moreover in the preterminal region, anastomosed tubules of the SER formed a subsurface 'primary network' and gave rise to a deeper 'secondary network' made of thinner tubules; synaptic vesicles bulging at the tip of thin tubules of the SER were frequently observed. To specify the role played by the SER in the fast axonal transport, chicken ciliary ganglia were slighty compressed and radioautographed 3 h after the intracerebral injection of [3-H]lysine. Quantitative analysis of the silver grain distribution indicated that labeled proteins, rapidly conveyed down the axon, piled up in regions containing an accumulation of SER profiles. On the basis of these results, it is concluded that: (1) the SER appears as a continuous intraaxonal pathway bridging the perikaryon and the axon terminal; (2) the SER conveys macromolecular components with the fast axonal transport; (3) the conveyed macromolecules, which are delivered to the axonal membrane and to the synaptic vesicles, are probably transferred by means of connections with the SER.
Animals↗
Regeneration of motor axons in the rat sciatic nerve studied by labeling with axonally transported radioactive proteins.
Labeling regenerating axons with axonally transported radioactive proteins provides information about the location of the entire range of axons from the fastest growing ones to those which are trapped in the scar. We have used this technique to study the regeneration of motor axons in the rat sciatic nerve after a crush lesion. From 2 to 14 days after the crush the lumbar spinal cord was exposed by laminectomy and multiple injections of [3H]proline were made stereotactically in the ventral horn. Twenty-four hours later the nerves were removed and the distribution of radioactivity along the nerve was measured by liquid scintillation counting. There was a peak of radioactivity in the regenerating axons distal to the crush due to an accumulation of label in the tips of these axons. After a delay of 3.2 +/- 0.2 (S.E.) days, this peak advanced down the nerve at a rate of 3.0 +/- 0.1 (S.E.) mm/day. The leading edge of this peak, which marks the location of the endings of the most rapidly growing labeled fibers, moved down the nerve at a rate of 4.4 +/- 0.2 mm/day after a delay of 2.1 +/- 0.2 days; this is the same time course as that of the most rapidly regenerating sensory axons in the rat sciatic nerve, measured by the pinch test. Another peak of radioactivity at the crush site, presumed to represent the ends of unregenerated axons or misdirected sprouts, declined rapidly during the first week, and more slowly thereafter.
Animals↗
Progressive deficits in retrograde axon transport precede degeneration of motor axons in acrylamide neuropathy.
Single injection of acrylamide (1.3 mmol/kg, i.p.) inhibited retrograde axon transport of [125I]tetanus toxin in hen sensory and motor axons. Retrograde axon transport deficits appeared within hours of dosing with acrylamide. The inhibitory effect of acrylamide on retrograde axon transport was transient since transport deficits were not detectable 35 h after dosing. Acrylamide impaired the retrograde movement but not the uptake of [125I]tetanus toxin in the axon. Multiple doses of acrylamide (0.42 mmol/kg, i.p.) induced progressive clinical signs of acrylamide neuropathy that correlated with increasing deficits in retrograde axon transport of [125I]tetanus toxin to ventral spinal cord. Deficits were also observed in sensory neurons but were not statistically significant. Accumulated decrements in retrograde axon transport may be the underlying cause of degeneration of motor axons in acrylamide neuropathy in fowl.
Acrylamide↗
Neuronal dynamics and axonal flow. IV. Blockage of intra-axonal enzyme transport by colchicine.
The fact that the nucleated center of the nerve cell is the major source of the macromolecular materials required in the maintenance and function of the whole neuron requires the operation of a steady cellulifugal convection of these supplies into and down the nerve fiber. This proximo-distal traffic has been firmly established, but the mechanisms involved in it are still poorly understood. Besides the slow (ca. 1 mm per day) advance of the axonal column as a whole ("axonal flow" in the strict sense), the demonstration of additional, much faster, traffic rates (up to several cm per day) calls for special conduits within the axon ("intra-axonal flow"). To test the possible role of neurotubules (average width:220 A) in this traffic, the drug colchicine, known for its immobilizing effect on microtubules in other types of cells, was locally injected into peripheral nerves. This resulted in a major blockage of the proximo-distal movement of a test enzyme, acetylcholinesterase, into and through the injected zone, the extent of blockage varying with the applied dosage. By analogy, the neurotubules thus seem to be definitely implicated in the motile mechanism of intra-axonal transport. By contrast, the movement of a mitochondrion-associated marker enzyme, diphosphopyridine nucleotide diaphorase, was not perceptibly affected (in the submaximal dosage range), which seems to signify that the proximo-distal shift of mitochondria, for which the slow axonal flow acts as carrier, has gone on uninterruptedly. The experiments thus indicate the possibility of uncoupling the axonal and intra-axonal transport mechanisms.
Acetylcholinesterase↗
Changes in axon size and slow axonal transport are related in experimental diabetic neuropathy.
In the sciatic system of rats with streptozocin (SZ)-induced diabetes, delay of axonal transport of neurofilament (NF) proteins, tubulin, and other proteins is associated with a change in axonal caliber, which increases by 40% in lumbar motor roots and decreases by 36% in tibial nerves. Since in large myelinated axons caliber is a function of the number of NF, which, in turn, is regulated by axonal transport, we studied the correlation of the number of NF and microtubules (MT) with axonal cross-sectional area in the sciatic system of SZ-treated rats to investigate whether the changes in caliber could be attributed to the impairment of transport. Despite the changes in cross-sectional area, diabetic axons in both proximal motor roots and distal tibial nerves maintained the ratios of number of NF and MT to cross-sectional area found in controls. Our findings suggest that, in rats with SZ-induced diabetes, the proximal and distal alterations of axonal caliber are an adjustment to the change in number of NF and/or MT that results from the impairment of the slow axonal transport.
Animals↗
Fast axonally transported proteins in regenerating goldfish optic axons.
Fast axonal transport of protein was examined in regenerating goldfish optic axons after a lesion of either the optic tract or optic nerve, which revealed changes in the original intact optic axon segments or in the newly regenerated axon segments, respectively. In animals killed either 6 or 24 hr after injection of 3H-proline into the eye, labeling of total fast-transported protein in the original axon segments was increased by 2 d after the lesion, reached a peak of nearly 20 X normal at 2 weeks, and then declined to a level somewhat above normal at 12 weeks. When the labeling of individual transported proteins was examined by 2-dimensional gel electrophoresis, it was found that no new labeled proteins appeared during regeneration, but all proteins examined showed an increase in labeling. Among the various proteins, there was great variation in the magnitude and time course of the labeling increase. The largest increase, to nearly 200 X normal with 6 hr labeling, was seen in a protein with a molecular weight of 45 kDa and a pl of about 4.5, resembling a protein that has previously been designated a "growth-associated protein" (GAP-43; Skene and Willard, 1981a). The proteins showing increased labeling included a small fraction of cytoskeletal proteins (alpha-tubulin, beta-tubulin, and actin) that was apparently transported at a much faster rate than is usually expected of these constituents. In the new axon segments, the total protein labeling was increased by 1 week after the lesion, remained elevated at a nearly constant level of about 7 X normal from about 2 to 5 weeks, and then declined to levels somewhat above normal by 12 weeks. The 45 kDa protein again showed the largest increase, and became the single most prominently labeled constituent in the new axons. On the basis of the time course of labeling in both original and new axon segments during regeneration, the fast-transported proteins were tentatively separated into 5 classes that may represent groups of proteins that are coregulated during regeneration. They may conceivably correspond to different functional or structural entities within the neuron.
Animals↗
Relations between cell body size, axon diameter and axon conduction velocity of triceps surae alpha montoneurons during the postnatal development in the cat.
Triceps surae alpha-motoneurons in cats of different postnatal ages were stained intracellularly with horseradish peroxidase (HRP) and studied light microscopically. In individual neurons, the mean diameter of the cell body and the intramedullary axon diameter were measured and related to the axon conduction velocity. The mean diameter of the cell body grew from 39.6 micrometer at birth to 57.6 micrometer in the adult cat, while the corresponding figures for the intramedullary axon diameters were 2.4 micrometer and 6.7 micrometer. During the same period of time, the axon conduction velocity increased from 11.3 m/s to 93.5 m/s, and the ratio between the conduction velocity and the intramedullary diameter of the axon (CV/d ratio) increased from 4.6 to 14.1. The results indicate that the growth of the cell body is smaller and completed earlier than the growth in diameter of the intramedullary and, in particular, the peripheral parts of the axon. The considerable change of the CV/d ratio during the postnatal development may be explained by previously described immature morphological properties of the axons in very kittens, and by a changing relation between the dimensions of the intramedullary and peripheral parts of the axon.
Animals↗
Decreased axonal calibres without axonal loss in optic nerve following chronic alcohol feeding in adult rats: a morphometric study.
The effects of chronic ethanol exposure on number and calibres of optic nerve axons (and number of retinal ganglion cells) were investigated in a rat model. Male Sprague-Dawley rats were fed a liquid, ethanol-containing diet for 5, 10 and 17 weeks with littermates given isocaloric amounts of ethanol-free diet serving as controls. After fixation by perfusion, the optic nerves were imbedded in epoxy resin and sectioned for electron microscopy. Systematic random sampling was made from a cross-shaped area over the nerve. Axons within a counting frame were counted and morphometrically categorized with regard to mean diameter and the total number of axons estimated from number per area and the cross-sectional area of the nerve, which was measured using a digitizer table. According to non-parametric statistical analysis, ethanol exposure resulted in a significant reduction in mean cross-sectional area of the optic nerve and in mean axonal calibre but not in total axonal number in the ethanol-treated rats but there was no significant effect of duration of the exposure. The mean cross-sectional area of the nerve was reduced by 9%, 10% and 18% after 5, 10 and 17 weeks of exposure, respectively. The reduction in cross-sectional area appeared to be related to a proportional reduction in axonal and myelin area fractions. The findings indicate that chronic ethanol exposure results in decreased axonal calibres without axonal loss. This also implies that there is no reduction in the number of retinal ganglion cells.
Animals↗
Age-related and region-specific increase in number of concentric lamellar bodies in axon terminals and presynaptic axons in central nervous system of groggy mutant rat.
In some regions of the central nervous system (CNS) of the groggy rat, a mutant with a movement disorder, concentric lamellar bodies (CLBs) were formed in numerous axon terminals and presynaptic axons. These bodies were counted electron microscopically in the lateral cerebellar nuclei of Slc:Wistar and groggy mutant rats at 20 to 180 days of age. In the Slc:Wistar rat groups, the mean numbers of axonal CLBs were mostly under 1.0 per 100 microns2, except for the 30-day-old rat group which showed a value of 1.7. In the groggy rat groups, the numbers of axonal CLBs greatly increased from 40 days of age onward, reaching the maximum mean number of 23.7 per 100 microns2 in the 90-day-old rat group and subsequently decreasing; however, significant numbers were still present in the 180-day-old rat group. Since these bodies have been reported to contain an acid phosphatase (ACPase), the regional specificity of their appearance in the CNS was examined by light and electron microscopic ACPase histochemistry. In the 90- and 180-day-old groggy rats, numerous particulate deposits of ACPase reaction products were found in the neuropil of the lateral, interposed and medial cerebellar nuclei, the superior, lateral and spinal vestibular nuclei, and the spinal gracile nuclei. By electron microscopy, the particulate deposits in the cerebellar and vestibular nuclei were confirmed as the CLBs in axon terminals, while those in the gracile nuclei were revealed to be the dystrophic axons. Thus, it was suggested that the axon terminals and presynaptic axons, having a high capacity to form the CLBs in the groggy rats from 40 days of age onward, belong to the Purkinje cells.
Acid Phosphatase↗
Smaller axon and unaltered numbers of microtubules per axon in relation to number of myelin lamellae of myelinated fibers in the mutant quail deficient in neurofilaments.
To characterize the morphological features of the myelinated fibers in the mutant quails deficient in neurofilaments (NF), caused by a nonsense mutation in the NF-L gene, the morphological parameters of the axon and myelin sheath, and their relationships in the peroneal nerve were evaluated. In the mutant, the axonal area was smaller than in the control (P > 0.01), reflecting the lack of large diameter axons. There was no significant difference in the mean number of myelin lamellae and of their spacings between controls and mutants. Therefore, it was decided to analyze the alteration of axonal parameters in relation to the number of myelin lamellae. In the regression analysis, the number of microtubules (MT) per square micrometer of the axonal area was greater in the mutant than in the control (P < 0.05); however, the number of MT per axon was similar in controls and mutants with the same given number of myelin lamellae. The number of MT+NF per axon was smaller in the mutant than in the control only for myelinated fibers with more than 25 myelin lamellae (P > 0.05). These findings indicate that there was a less significant effect of NF deficiency on the smaller than on the larger myelinated fibers. There was no compensatory increase in the numbers of MT per axon of the myelinated fibers in the mutant as found previously in the unmyelinated fibers of the mutant.
Animals↗