Search PubMed⌕ Search

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.

At least 343 records · Page 19Linked to original sources
PubMed2002

Calcium/calmodulin-dependent protein kinase IIbeta isoform is expressed in motor neurons during axon outgrowth and is part of slow axonal transport.

Previously, we identified calcium/calmodulin-dependent protein kinase IIbeta (CaMKIIbeta) mRNA in spinal motor neurons with 372 bp inserted in what corresponds to the "association" domain of the protein. This was interesting because known additions and deletions to CaMKIIbeta mRNA are usually less than 100 bp in size and found in the "variable" region. Changes in the association domain of CaMKIIbeta could influence substrate specificity, activity or intracellular targeting. We show that three variations of this insert are found in CNS neurons or sciatic motor neurons of Sprague-Dawley rats. We used PCR and nucleic acid sequencing to identify inserts of 114, 243, or 372 bases. We also show that addition of the 372 bases is associated with outgrowth of the axon (the standard CaMKIIbeta downregulates when axon outgrowth occurs). Radiolabeling, immunoblots, and 2D PAGE identified this larger CaMKIIbeta as part of the group of soluble proteins moving at the slowest rate of axonal transport (SCa) in sciatic motor neurons (similar1 mm/day). This group is composed mainly of structural proteins (e.g., tubulin) used to assemble the cytoskeleton of regrowing axons.

Amino Acid Sequence↗
PubMed1992

Acrylamide exposure preferentially impairs axonal transport of glycoproteins in myelinated axons.

The right L5 dorsal root ganglion of adult rats exposed to acrylamide (40 mg/kg body weight/day for nine consecutive days) was injected with either [3H]methionine or [3H]glucosamine. After allowing incorporation into macromolecules and axonal transport to proceed for 5 hr, the distribution of radioactivity in cross sections and longitudinal sections of sciatic nerve was determined by autoradiography. Control and treated animals showed no difference in distribution of label within the sciatic nerve with respect to rapidly transported proteins labelled with [3H]methionine. In control animals the distribution of rapidly transported glycoproteins labelled with [3H]glucosamine was similar to that found for [3H]methionine-labelled proteins. In contrast, acrylamide-exposed rats had a very different distribution of labelled glycoproteins; there was a marked paucity of label in the myelinated axons. We interpret this result as indicating that acrylamide preferentially inhibits glycosylation or axonal transport of glycoproteins in neurons bearing myelinated axons.

Acrylamide↗
PubMed1978

Axonal transport of lipid in goldfish optic axons.

After injection of labeled glycerol, choline, or serine into the eye of goldfish, labeled lipids were axonally transported along the optic nerve to the optic tectum. Although the different precursors were presumably incorporated into somewhat different lipid populations, all three were approximately equally effective in labeling the lipids transported to the tectum, but the amount of transported material remaining in the nerve was different, being highest with choline and lowest with serine. The labeled lipids appeared in the tectum within 6 hr of the injection, indicating a fast rate of transport, but continued to accumulate over a period of 1--2 weeks, which presumably reflects the time course of their release from the cell body. Since there was a gradual increase in the proportion of labeled lipid in the tectum during this period, some other process in addition to fast axonal transport may have affected the distribution of the lipids along the optic axons. When [3H]choline was used as precursor, the transported material included a small amount of TCA-soluble material, which was probably mainly phosphorylcholine, with labeled acetylcholine appearing in only insignificant amounts. With serine, which gave rise to a large amount of axonally transported protein in addition to lipid, a late increase in the amount of labeled lipid in the tectum was seen, accompanied by a decrease in labeling of the protein fraction.

Acetylcholine↗
PubMed1980

The short term accumulation of axonally transported organelles in the region of localized lesions of single myelinated axons.

Myelinated axons were isolated from the sciatic nerve of Xenopus laevis and were subjected to localized (less than 30 microns wide) lesions. In axons which were bathed in a 0.12 M potassium glutamate solution there was very little local reaction to the lesion and optically-detectable particles undergoing axoplasmic transport accumulated immediately adjacent to, and mostly distal to, the lesion. Preparations fixed for electron microscopy at times up to 3 h following the lesion showed that the axoplasmic changes about the lesion were asymmetrical. Large organelles predominated on the distal side of the lesion; these were mostly dense lamellar bodies (DLB) with mean dimensions, as determined from thin sections, of 0.48 by 0.19 microns. Multivesicular bodies, mitochondria, and a variety of smaller membrane bounded bodies also appeared in the particle accumulation distal to the lesion. Analysis of these results led to the conclusion that DLB were transported up to the lesion and represent the majority of the optically detectable particles which are transported in the retrograde direction. Small vesicles and tubules were the commonest structures which accumulated proximal to the lesion. The time course of this accumulation was consistent with the hypothesis that these structures are particulate bodies which move in the orthograde direction at about 1.5 microns/s. Incidental findings which are also of significance to the study of axonal transport were: large particulate material may reverse its direction of movement at an axonal obstruction, and organelles which accumulate on either side of a lesion do so in rows which are associated with microtubules.

Animals↗
PubMed1984

An anterograde neuroanatomical tracing method that shows the detailed morphology of neurons, their axons and terminals: immunohistochemical localization of an axonally transported plant lectin, Phaseolus vulgaris leucoagglutinin (PHA-L).

A new neuroanatomical method for tracing connections in the central nervous system based on the anterograde axonal transport of the kidney bean lectin, Phaseolus vulgaris-leucoagglutinin (PHA-L) is described. The method, for which a detailed protocol is presented, offers several advantages over present techniques. First, when the lectin is delivered iontophoretically, PHA-L injection sites as small as 50-200 micron in diameter can be produced, and are clearly demarcated since the neurons within the labeled zone are completely filled. Second, many morphological features of such filled neurons are clearly demonstrated including their cell bodies, axons, dendritic arbors and even dendritic spines. Third, there is some evidence to suggest that only the neurons at the injection site that are filled transport demonstrable amounts of the tracer, raising the possibility that the effective injection site can be defined quite precisely. Fourth, even with the most restricted injections, the morphology of the labeled axons and axon terminals is clearly demonstrated; this includes boutons en passant, fine collateral branches, and various terminal specializations, all of which can be visualized as well as in the best rapid Golgi preparations. Fifth, when introduced iontophoretically, PHA-L appears to be transported preferentially in the anterograde direction; only rarely is it transported retrogradely. Sixth, PHA-L does not appear to be taken up and transported effectively by fibers of passage. Seventh, there is no discernible degradation of the transported PHA-L with survival times of up to 17 days. Finally, since the transported marker can be demonstrated with either peroxidase or fluorescent antibody techniques, it may be used in conjunction with other neuroanatomical methods. For example, double anterograde labeling experiments can be done using the autoradiographic method along with immunoperoxidase localization of PHA-L, and the retrogradely transported fluorescent dyes can be visualized in the same tissue sections as PHA-L localized with immunofluorescence techniques.

Animals↗
PubMed1992

Does GAP-43 support axon growth by increasing the axonal transport velocity of calmodulin?

GAP-43 is a neuronal protein whose synthesis is elevated during developmental and regenerative axon growth. We propose that one consequence of this increased synthesis may be the delivery of calmodulin-like proteins to the distal portions of the growing axon at an increased velocity; this is because calmodulin, which is transported slowly in mature intact axons, can bind to GAP-43, which is transported rapidly. The release of calmodulin from GAP-43 would be regulated by phosphorylation by protein kinase C. Such a rapid carrier function could be important for allowing certain recently synthesized slowly transported proteins to reach the moving growth cone in time to support its function. This hypothetical carrier mechanism is consistent with the phosphorylation pattern, calmodulin binding, transport velocity, and growth-association of GAP-43, and suggests an explanation for the specific importance of newly synthesized GAP-43 in supporting axon growth.

Animals↗
PubMed1975

The slow component of axonal transport. Identification of major structural polypeptides of the axon and their generality among mammalian neurons.

This study of the slow component of axonal transport was aimed at two problems: the specific identification of polypeptides transported into the axon from the cell body, and the identification of structural polypeptides of the axoplasm. The axonal transport paradigm was used to obtain radioactively labeled axonal polypeptides in the rat ventral motor neuron and the cat spinal ganglion sensory neuron. Comparison of the slow component polypeptides from these two sources using sodium dodecyl sulfate (SDS)-polyacrylamide electrophoresis revealed that they are identical. In both cases five polypeptides account for more than 75% of the total radioactivity present in the slow component. Two of these polypeptides have been tentatively identified as tubulin, the microtubule protein, on the basis of their molecular weights. The three remaining polypeptides with molecular weights of 212,000, 160,000, and 68,000 daltons are constitutive, and as such appear to be associated with a single structure which has been tentatively identified as the 10-nm neurofilament. The 212,000-dalton polypeptide was found to comigrate in SDS gels with the heavy chain of chick muscle myosin. The demonstration on SDS gels that the slow component is composed of a small number of polypeptides which have identical molecular weights in neurons from different mammalian species suggests that these polypeptides comprise fundamental structures of vertebrate neurons.

Animals↗
PubMed1987

Acrylamide neuropathy: changes in the composition of proteins of fast axonal transport resemble those observed in regenerating axons.

Proteins conveyed by fast axonal transport along sensory and motor axons of rat sciatic nerve were labelled with L-[35S]methionine and characterized by one- and two-dimensional electrophoresis on polyacrylamide gels, followed by fluorography. Nerves from normal or bis-acrylamide-treated animals were compared with nerves from acrylamide-treated animals and nerves regenerating after a crush axotomy. In both sensory and motor axons significant changes in the pattern of labelled bands on one-dimensional gels occurred after 10 days of acrylamide treatment (50 mg/kg daily, i.p.). These changes resembled those seen in regenerating axons, but were less pronounced. No changes were detectable after shorter periods of treatment, even though the onset of the neuropathy, assessed by a behavioral test, occurred on days 4-6 of treatment. Two-dimensional separations of the labelled proteins revealed increased labelling of growth-associated protein 43 in acrylamide-treated animals, but again this was less pronounced than in regenerating nerves. Acrylamide treatment induces changes in composition of fast-transported protein that are qualitatively similar to those seen after axotomy. Since these changes are not detectable until the neuropathy is advanced, it is unlikely that they are causative factors. Instead, they are most likely a result of the cell body reaction previously observed in acrylamide intoxication, a reaction that resembles that produced by axotomy.

Acrylamide↗
PubMed1998

The delayed depolarization in rat cutaneous afferent axons is reduced following nerve transection and ligation, but not crush: implications for injury-induced axonal Na+ channel reorganization.

Two distinct populations of Na+ channels (kinetically fast and slow) are present on the cell bodies and axons of cutaneous afferent neurons; the fast current is increased and the slow current reduced in amplitude following nerve injury. The present study was undertaken to determine if similar changes occur on the axons of these neurons following peripheral nerve injury. The compound action potentials from rat sural nerves were recorded in a sucrose gap chamber. Following application of 4-aminopyridine, a prominent and well-characterized depolarization (the delayed depolarization) followed the action potential. This potential, only present on cutaneous afferent axons, has been correlated with activation of a slow Na+ current. The delayed depolarization was reduced after nerve transection. The refractory period of transmission of the action potential was shortened in the transected nerves, but that of the delayed depolarization was prolonged. The changes were largest when the sural nerve was cut and ligated [control: 38.1 +/- 1.7% (n = 5); injury: 24.5 +/- 2.8% (n = 5), P < 0.05], which prevented reconnection to its peripheral target. When the nerve was crushed and allowed to reestablish peripheral target connections, the delayed depolarization was minimally effected. These results indicate that the changes in Na+ channel organization following peripheral target disconnection observed on cutaneous afferent cell bodies also occur on their axons.

4-Aminopyridine↗
PubMed1995

Acute axonal Guillain-Barré syndrome with IgG antibodies against motor axons following parenteral gangliosides.

We studied 7 patients with an acute motor axonal Guillain-Barré syndrome (GBS), manifested 5 to 15 days after parenteral injection of a commercial ganglioside preparation given for nonspecific pain syndromes. The serum IgG and IgM antibody response to ganglioside was studied serially and the recognition of epitopes on the peripheral nerves and motor end-plates was examined using biotinylated IgG extracted from the patient's serum. Sera from 8 patients treated with the same ganglioside preparation who did not develop neuropathy and from 25 patients with classic GBS never treated with gangliosides were studied concurrently. All patients with ganglioside-related GBS had a rather severe axonal degeneration, incomplete recovery, and high IgG, but not IgM, antiganglioside antibody titers, ranging from 1:320 to 1:10,240. Seven (28%) of the 25 GBS patients had IgG antibody titers, ranging from 1:160 to 1:10,240. None of the ganglioside-treated patients who did not develop GBS and none of the 50 disease control subjects had IgG GM1 antibodies. Purified IgG from the patients with high GM1, antibodies, but not from the others, recognized epitopes at the nodes of Ranvier and the distal motor nerve terminals at the end-plate. We conclude that exogenous ganglioside injections can be immunogenic, triggering IgG antiganglioside antibodies with specificity for motor nerve-terminals. In some patients with axonal GBS such antibodies may be markers or mediators of axonal involvement.

Antibodies↗
PubMed1975

Horizontal cell axons and axon terminals in goldfish retina.

Retinas of ordinary and black moor varieties of goldfish (Carassius auratus) were prepared by the Golgi method, mounted flat or sectioned vertically, and studied in the light microscope. Three types of horizontal cells whose dendrites contact only cones, and one type whose dendrites contact only rods, were observed. The cone horizontal cells (Cajal's "external horizontal cells") all have slender axons which descend gradually to the inner nuclear layer and terminate there in long, fusiform expansions (Cajal's "internal horizontal cells"). The thin and thick portions of the axons, as well as the perikarya of the horizontal cells, bear small numbers of straight, horizontally-directed, knobby filamentous appendages which may be sites of synaptic contact. The cone horizontal cell axons in goldfish, unlike those in higher vertebrates, do not terminate in contact with synaptic endings of photoreceptor cells, but in proximity to cells and processes deep in the inner nuclear layer. Axons have not yet been demonstrated on rod horizontal cells in goldfish.

Animals↗
PubMed1982

The structural correlate of saltatory conduction along the Mauthner axon in the tench (Tinca tinca L.): identification of nodal equivalents at the axon collaterals.

The spiny collaterals of the Mauthner axon were reinvestigated in the tench (Tinca tinca L.) with the electron microscope and special staining procedures. These collaterals, as demonstrated by intraaxonal labelling with lucifer yellow, are more or less regularly spaced (100-300 micrometers) and make synaptic contacts with processes of spinal motoneurons and interneurons. The unmyelinated tips of the collaterals are further characterized by the following structural features: (1) an electron-dense undercoating of the axolemma, (2) a positive Prussian blue reaction of the inner surface of the axolemma following ferric ion-ferrocyanide staining (Waxman and Quick, '78a), (3) expanded extracellular spaces which react specifically to inorganic phosphate, metallic ions, and diaminobenzidine. All these properties are known to be shared by the axolemma of central and peripheral nodes of Ranvier. Previous studies from this laboratory have shown that the nerve impulse is propagated along the Mauthner axon in a saltatory mode. Since classical nodal gaps could not be identified within the myelin sheath of this giant fiber, it is concluded on the basis of the present findings that the unmyelinated tips of the spiny collaterals represent nodal equivalents, and thus provide the morphological substrate for the saltatory propagation of the nerve impulse along the Mauthner axon. The typical latency steps, as demonstrated in the latency plot of the longitudinal current signals (Greeff and Yasargil, '80), and the distances between the identified membrane specializations at the axon collaterals are consistent with this conclusion.

Animals↗
PubMed1983

Investigations on the development and topographic order of retinotectal axons: anterograde and retrograde staining of axons and perikarya with rhodamine in vivo.

Rhodamine-B-isothiocyanate (RITC) is shown to be a convenient and advantageous fluorescence tracer both for anterograde staining of retinal ganglion cell axons on the tectum and for retrograde staining of ganglion cell bodies in the retina of chick embryos. After intravitreal injection the dye is taken up by ganglion cells of the retina from the extracellular space and is transported anterogradely at about 10 mm/day up to the axonal growth cones on the tectum. RITC can be taken up by growing axons on the tectum and it is transported retrogradely at about 5 mm/day to the cell bodies in the retina. Local staining can be achieved if RITC is applied in its crystalline form. RITC is nontoxic for the cells and their axons, is resistant to histological fixation procedures, and allows quick observation in vivo and on dissection stained tissue. Local application of RITC to distinct retinal areas allows examination of the position of the corresponding stained fibers along the retinotectal pathway. Fibers which arise from the central temporal retina occupy deeper layers, whereas fibers from the peripheral temporal retina occupy more superficial layers in the optic tract and in the stratum opticum on the anterior tectum. The growth cones of early retinal fibers growing directly on the tectal surface show a different morphology to later growth cones growing on top of the stratum opticum on the tectum.

Animals↗
PubMed1987

Morphological and physiological studies of rod-driven horizontal cells with special reference to the question of whether they have axons and axon terminals.

Rod-driven (intermediate) horizontal cells were examined in the carp retina to determine whether they bear axons and axon terminals. These cells were injected with HRP after physiological identification of the response type; which consisted of a higher sensitivity to light and a slower response time course than cone-driven (external) horizontal cells, and spectral sensitivity peaking at 520 nm. The labeled cells were further identified morphologically by tracing their dendrites to rod photoreceptors by light and electron microscopy. About two-thirds of the labeled cells (18/30) had a slender, axonlike process (less than 1 micron in diameter, 70-300 micron in length) running horizontally from the soma. No axonlike process was found in the remaining cells. Unlike the axons of external horizontal cells, this axonlike process was short and did not form a long fusiform expansion. No membrane specialization was found along the axonlike process. Since it has been reported that the syncytium made of axon terminals of external horizontal cells serves as a signal bypass of the syncytium made of the somata, it was asked, in separate experiments, whether the intermediate horizontal cells also had such a double syncytial layer. Response amplitudes to a slit of light were measured by placing the slit at various distances from the recording electrode. The response amplitude decayed with distance with a single exponential function, indicating that the syncytium of intermediate horizontal cells consists of a monolayer. These physiological data are consistent with the morphological observations.

Animals↗
PubMed1994

Cytoarchitectonic development, axon-glia relationships, and long distance axon growth of porcine striatal xenografts in rats.

Porcine fetal lateral ganglionic eminence cells were transplanted into the quinolinic-acid-lesioned corpus striatum of immunosuppressed adult rats. The resulting grafts were analyzed for graft development with respect to donor age, donor cell dosage, and survival time from 5 to 22 weeks postimplantation. Graft development is prolonged by a factor of 3-4 times in porcine xenografts as compared to rat allografts. As grafts matured, neuronal somata developed in clusters that expressed acetylcholinesterase (AChE), tyrosine hydroxylase, and dopamine- and cAMP-associated phosphoprotein. These clusters were interspersed with AChE-poor graft regions consisting of small densely packed cells that stained for glial fibrillary acidic protein and porcine cluster of differentiation factor 44 (a species-specific glial marker). Graft axons could be selectively stained for 70-kDa neurofilament and were preferentially associated with AChE-poor, glial-rich regions in younger grafts (8 weeks), but AChE-rich neuronal regions in older grafts (22 weeks). Both graft axons and graft glial fibers projected for long distances into the host internal capsule, external capsule, corpus callosum, and anterior commissure. Donor axons also innervated host target structures including the globus pallidus and substantia nigra. This demonstrates a prolonged development of striatal cells that is appropriate to the donor species and which produces long-distance target-specific axonal growth within the adult host brain.

Animals↗
PubMed1985

Axonal degeneration distal to the site of accumulation of vesicular profiles in the myelinated fiber axon in experimental isoniazid neuropathy.

Morphometric sequential studies of pathologic changes were carried out on myelinated fibers in the lumbar ventral root of Sprague-Dawley rats administered with isoniazid, 1,500 mg/kg body weight, in a single dose. Accumulation of axoplasmic organelles with secondary paranodal retraction of myelin sheath occurred in the middle part of the ventral root as early as day 2 after the administration. On day 3, axonal degeneration started to occur, distal to the middle part, where the accumulation of axoplasmic organelles is prominent. Such accumulation with the possible blockade of the fast axoplasmic transport in the proximal axon may be directly responsible for the distal axonal degeneration. Alternatively such accumulation may be secondary to the distal axonal degeneration. The morphological sequential findings described clearly reflects the pathological events in isoniazid neuropathy.

Animals↗
PubMed1988

Abnormalities of the axonal cytoskeleton in giant axonal neuropathy.

Intermediate filaments accumulate abnormally in a variety of cell types in individuals with human inherited giant axonal neuropathy (GAN). A characteristic feature of this disorder is the occurrence of focal axonal enlargements filled with accumulations of neurofilaments. The minimum separations between neurofilaments in sural nerve axons of a patient with GAN were 12-30 nm compared with 24-60 nm in controls. The normal sidearm protrusions which cross-bridge adjacent filaments were rare in GAN. Average minimum neurofilament diameter was 12.4 nm in GAN compared with 10.1 nm in controls. Many axons were devoid of neurofilaments and contained an increased density of microtubules, many of which did not run longitudinally. This disorganization of microtubule alignment may reflect the lack of an associated neurofilament lattice. It is concluded that GAN involves abnormalities of neurofilament cross-linkage to one another and to adjacent microtubules. Mechanisms are discussed which could account for this inherited disorder of intermediate filament organization affecting various cell types.

Adult↗
PubMed1979

Extra-axonal diffusion in the rabbit optic system: a caution in axonal transport studies.

The hazards of using optic nerve (as opposed to optic tract and more distal components of the optic system) to study axonal transport were highlighted by observing the fate of [14C]serine and [3H]glycerol injected into the rabbit eye. Despite prior blockage of axonal transport with colchicine, appreciable radioactivity rapidly appeared in the optic nerve adjacent to the injected eye. Radioactivity decreased exponentially along the entire optic chiasm. Counts were distributed among the lipid, protein, and acid-soluble fractions. Separation of optic nerve lipids revealed appreciable labeling of most lipid classes including those characteristic of myelin; a markedly different labeling pattern was observed for axonally transported lipids. The data are consistent with a mechanism involving extra-axonal diffusion of precursor into the surrounding glia followed by incorporation into lipids and proteins of those cells and ultimately myelin. The phenomenon is discussed in relation to possible errors that were made in interpreting earlier experiments.

Animals↗