Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Axonal Transport”

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 883 records · Page 49Linked to original sources
PubMed1986

The retrograde fast component of axonal transport in motor and sensory nerves of the rat during administration of 2,5-hexanedione.

The retrograde and anterograde fast component of axonal transport (rFC and aFC) were examined in rats following intoxication with 2,5-hexanedione (1 g/kg/week) for 2, 4, 6 and 8 weeks. rFC and aFC were measured as accumulations distal and proximal to a double ligature after labeling of protein by injection of [35S]methionine into L5 spinal cord or L5 dorsal root ganglion. Clinical symptoms appeared after an accumulated dose of 6 g/kg of the toxin and was dominated by motor deficiencies. Abnormalities in retrograde build-up appeared earliest in motor nerves after an accumulated dose of 4 g/kg, while the sensory nerves showed a decreased retrograde build-up only after 6 g/kg. In motor nerves retrograde build-up for the short and the long accumulation interval (11.5-17.5 h and 11.5-25.5 h, respectively) was equally depressed, while in sensory nerves the retrograde build-up for the early accumulation interval (10-16 h) was less severely depressed as compared to the late collection interval (10-24 h). These findings point to a decreased amount of rFC, rather than a delay in turn-around. Furthermore, build-up was inversely correlated with the dose of 2,5-hexanedione and was most pronounced in motor nerves (82% vs 52% in motor and sensory nerves, respectively) at the final dose of 8 g/kg. When intoxication was stopped, rats improved in muscle-strength, but still showed atrophy of leg muscles. Coincidently, retrograde transport in motor nerves was normalized for the short accumulation interval, and improved for the longer collection interval, though not completely normalized.

Animals↗
PubMed1981

The effect of ruthenium red on the assembly and disassembly of microtubules and on rapid axonal transport.

The assembly of microtubules was found to decrease in proportion to the mount of added ruthenium red, indicating a high affinity of ruthenium red for the microtubule system. An equimolar amount of ruthenium red per tubulin dimer inhibited the microtubule assembly completely and disassembled existing microtubules. Binding of ruthenium red to tubulin is accompanied by a shift in the absorption maximum fro 535 to 538 nm. The binding is very strong, as shown by the finding that ruthenium red could not be displaced from tubulin by gel chromatography on Sephadex G-25, or by the addition of Ca2+ or Mg2+. The binding of ruthenium red to tubulin did not affect the single colchicine site, nor the Mg2+ site(s), as shown by use of Mn2+ as an EPr probe. Ruthenium red also interfered with microtubules in an intact cell system, as it inhibited rapid axonal transport in the frog sciatic nerve, measured by the accumulation of [3H]leucine-labelled proteins in front of a ligature.

Animals↗
PubMed1988

Microtubule gelation-contraction in vitro and its relationship to component a of slow axonal transport.

Microtubule proteins, isolated by cycles of assembly, will undergo ATP-dependent gelation-contraction in vitro. A particulate component is present in these preparations, which is required for the gelation-contraction of microtubules assembled from purified tubulin. These particulates contain tubulin, neurofilament, spectrin, MAP2, and other as yet unidentified proteins. The particulates have a microtubule-stimulated ATPase that may be unique and is the likely motor for microtubule gelation-contraction. The basic structural unit of these particulates appears to be a crescent-shaped, or hemispherical, granule about 20 nm in diameter. The particles move along microtubule walls at a rate of about 1 micron. When compared to known physiological phenomena, microtubule gelation-contraction has striking similarities to component a of slow axonal transport (SCa), but displays no relationship to slow component b or to fast transport. On the basis of their similarities in composition, solubility, and rate of movement, we have proposed that the particulates responsible for microtubule gelation-contraction are the insoluble protein complexes, which have been suggested to be the transported component of SCa. We have termed these structures "slow component a particulates" or "SCAPs." It is probable that similar motile protein complexes exist in cells other than neurons, and we propose the term "dynasome" to describe such structures in general.

Animals↗
PubMed1981

Papain-derived fragment IIc of tetanus toxin: its binding to isolated synaptic membranes and retrograde axonal transport.

The papain-derived fragment IIc of tetanus toxin, which is immunologically identical to the B-IIb fragment, has previously been shown to bind gangliosides. As could be expected from its analogy with the B-IIb fragment, the IIc fragment was also found to bind to isolated synaptic membranes and to be transported retrogradely from the axonal endings within muscle to the motoneuronal perikarya. It is concluded that the IIc fragment--like the B-IIb fragment--might also serve as a specific carrier for chemical and chemotherapeutical agents into the central nervous system.

Afferent Pathways↗
PubMed1977

Fast axonal transport: effect of antimitotic drugs and inhibitors of energy metabolism on the rate and amount of transported protein in frog sciatic nerves.

Mitosis inhibitors, drugs affecting the energy metabolism, heavy water, and ouabain were used to partially inhibit fast axonal transport in frog sciatic nerves. Effects on the rate and on the amount of pulse labeled protein could be separated. The pulse of labeled protein, released after a cold-block, rapidly reached a maximum height which indicated that the transport system was saturated in the nerve segment occupied by the pulse. Both the rate and the amount were reduced by the mitosis inhibitors colchicine, vinblastine, and griseofulvin. Colchicine had a differential effect and reduced the rate of material migrating in the advancing front of the pulse less than the rate of that moving in the peak. Preincubation at low temperature potentiated the effects of colchicine. Two inhibitors of energy metabolism, NaCN and IAA, reduced the amount of labeled material in the pulse. The slope of the pulse was markedly reduced and multiple peaks appeared. The distance covered by the migrating pulse was largely unaffected, but some retardation of late components might have occurred. In contrast, 2.4-DNP reduced the rate without any effects on the amount of migrating material. Heavy water uniformly reduced the rate of the migrating pulse, whereas the main effect of ouabain was a diminished amount and multiple peaks as with NaCN and IAA. All drugs were tested for their effects on the electrical activity of sciatic nerves. The compound action potential was not affected by the mitosis inhibitors and heavy water, but was depressed by the inhibitors of energy metabolism and abolished by ouabain. The results indicate that the effects of various transport inhibitory drugs can be differentiated if both the rate and the amount are considered.

Action Potentials↗
PubMed1980

Effects of reserpine on fast, intermediate and slow axonal transport of proteins in rat locus coeruleus neurons.

The effects of a single injection of reserpine (5 mg/kg, i.p.) on protein turnover and axonal transport (AT) in locus coeruleus (LC) noradrenergic neurons was investigated in the rat. Reserpine pretreatment, at intervals of 1--21 days prior to [3H]-fucose or leucine injection into the LC, resulted in marked alterations in the turnover of [3H]glycoproteins and proteins in the LC and hypothalamus which were present for up to 14 days and varied according to the time after reserpine pretreatment. Reserpine produced an intermittent blockade, of variable degree, in rapidly and intermediately transported proteins for up to 2 weeks following injection. Slow AT was uniformly decreased over the first 10 post-treatment days to 2--42% of controls. Blockade and not a change in the rate or time of onset of transport appeared to be responsible for the observed changes. The suggested mechanism for these alterations is a re-ordering of metabolic priorities in the synthesis and transport of proteins in these noradrenergic cells secondary to a reserpine-induced depletion of norepinephrine in the nerve terminals.

Animals↗
PubMedDate not supplied

Cytofluorimetric scanning: a tool for studying axonal transport in monoaminergic neurons.

A new technique is described which makes it possible to measure several substances and parameters related to axonal transport in peripheral nerves. The technique is based on histofluorescent techniques and measures accumulated amounts of fluorescent substances, e.g. proximal to a crush or local cooling of the nerve. Sections from nerves, treated according to the FIF method for visualization of catecholamines or for immunofluorescence, are placed in a cytofluorimeter (Leitz MPV 2). The nerve sections are passed under a measuring slit by a motor-driven cross-table and the fluorescence intensity is continuously registered via a recorder with integrator which gives a graphical "nerve-accumulation profile." Comparisons between accumulation curves obtained with the cytofluorimetric scanning technique and biochemically determined accumulation curves of noradrenaline, dopamine-beta-hydroxylase and tyrosine-hydroxylase in the sciatic nerve following crush operations, demonstrated a striking similarity. With this technique it is possible to semiquantify the accumulated amount of a fluorescent substance, study morphology, perform morphometry and photographical documentation in the same section. This scanning technique may prove useful, since the accumulation and distribution of several substances in consecutive sections, along the length of a nerve, can be demonstrated graphically using superimposed curves.

Animals↗
PubMed1996

Effects of nerve growth factor on axonal retrograde transport after axonal injury of motoneurons.

In this experimental study we coupled nerve growth factor (NGF) with notatin by dicyclohexylcarbodiimide to label NGF and observed the effects of NGF on axonal retrograde transport after axonal injury of motoneurons with the aid of notatin chemiluminescence system. The results showed that NGF could be transported through axon not only to sensory neurons in dorsal root ganglia but also to motoneurons in spinal cord ventral horn.

Animals↗
PubMed1996

Increased neurite outgrowth of cultured rat dorsal root ganglion cells following transection or inhibition of axonal transport of the sciatic nerve.

Dissociated dorsal root ganglion cells (DRGs), taken from rats 2 weeks after sciatic nerve transection, have an increase in the percentage of cells with neurites compared to DRGs taken from normal animals. This study examines the possible factors that may contribute to the nerve injury-induced increase in neuritogenesis. Topical application of the local anaesthetic, bupivicaine, either to the nerve trunk prior to transection or to the proximal nerve stump for 2 weeks had no effect on the increased neurite outgrowth induced by nerve transection. Neurite outgrowth was also not influenced by administration of either nerve growth factor (NGF) via the femoral artery into normal rats or anti-NGF antiserum to the proximal nerve stump. Inhibition of axonal transport by topical application of vinblastine, however, induced a significant increase in neurite outgrowth compared to untreated controls. In addition, vinblastine-treated animals also develop hyperalgesia to mechanical stimulation and transganglionic labelling of sensory neurons with choleragenoid-horseradish peroxidase shows that the area of termination of myelinated sensory neurons in the spinal cord expands into lamina II. The results suggest that nerve injury-induced increase in neurite outgrowth is not dependent on NGF nor nerve impulses generated at the site of injury and supports the view that the absence of an inhibitory factor(s), that in normal animals may regulate neuronal outgrowth.

Anesthetics, Local↗
PubMed1975

A correlation between the effects of anti-mitotic drugs on microtubule assembly in vitro and the inhibition of axonal transport in noradrenergic neurones.

1. Podophyllotoxin, colchicine and griseofulvin inhibit the intra-axonal movement of noradrenaline storage vesicles in cat hypogastric nerve/inferior mesenteric ganglion preparations maintained in vitro, cause the disappearance of axonal microtubules and inhibit the assembly of microtubules from tubulin in vitro. The order of potency of the three effects is podophyllotoxin greater than colchicine greater than griseofulvin. 2. Lumicolchicine is without effect on the three parameters and does not interfere with the binding of tritiated colchicine to tubulin. 3. Podophyllotoxin causes a more rapid loss of microtubules from axons than the same concentration of colchicine. 4. The experiments provide strong evidence that microtubules are components of the system responsible for the intra-axonal migration of noradrenaline storage vesicles.

Animals↗
PubMed1985

Inhibition of the retrograde axonal transport of acetylcholinesterase by the anti-calmodulin agents amitriptyline and desipramine.

The possible involvement of calmodulin in mediating the calcium requirement for retrograde axonal transport of acetylcholinesterase was studied in vitro in bullfrog spinal nerves, with the use of the calmodulin inhibitors amitriptyline and desipramine. When nerves were preincubated with 0.2 mM amitriptyline or desipramine for 5 h, and were then ligated and incubated for an additional 17-18 h in drug-containing medium, the accumulation of acetylcholinesterase distal to the ligature was significantly reduced as compared to contralateral control nerves maintained in drug-free medium. The identical degree of transport inhibition observed for both drugs is consistent with their similar anti-calmodulin activity.

Acetylcholinesterase↗
PubMedDate not supplied

Heat shock protein 90 in retinal ganglion cells: association with axonally transported proteins.

The mRNAs for heat shock protein 90 (HSP90) are found at highest levels (differentially expressed) in the primate retinal fovea, the region of highest visual acuity, compared to the peripheral retina. HSP90 expression and retinal associations were analyzed by immuno-localization, in situ hybridization, and western analysis. Retinal ganglion cells (RGCs) express much of the HSP90 mRNA present in the primate retinal fovea. A large fraction of RGC synthesized HSP90 is apparently present in the axonal compartment. To identify the role of HSP90 protein in the optic nerve and retina, co-immunoprecipitation experiments were performed, using antibodies specific for HSP90 isoforms. The immunoprecipitates were analyzed for neurotrophin receptor and ligand activities, and MAP kinase activity. MAP kinase assay was used to determine the activation state of MAP kinase associated with HSP90. HSP90 proteins selectively associate with the inactive form of full-length tyrosine kinase growth factor receptor trkB, suggesting utilization during anterograde axonal transport. Activated MAP kinase, associated with the trk downstream signaling cascade, was found to co-immunoprecipitate with optic nerve HSP90, suggesting that HSP90 may be utilized in retrograde transport of the secondary messengers associated with neurotrophin signaling. HSP90 can thus be hypothesized to play a role in bidirectional RGC axonal protein transport.

Animals↗
PubMed1989

Calcitonin gene-related peptide and chromogranin A: presence and intra-axonal transport in lumbar motor neurons in the rat, a comparison with synaptic vesicle antigens in immunohistochemical studies.

The presence and intra-axonal transport of calcitonin gene-related peptide and chromogranin A were investigated in motor neurons belonging to the rat sciatic nerve. Their co-localization with markers of cholinergic organelles (SV2, p38, and synapsin I) was also investigated, using immunofluorescence techniques, including double labelling experiments. It was found that motor perikarya in the lumbar spinal cord contained calcitonin gene-related peptide-like immunoreactivity and chromogranin A-like immunoreactivity, and probably also caligulin-like immunoreactivity, located in the Nissl substance of the cytoplasm. Also, some SV2 (detected by the monoclonal antibody 10H) was present in some motor neuron perikarya, but most often these were devoid of SV2 and p38, as well as of synapsin I-like immunoreactivity. These three antigens were, on the other hand, concentrated in nerve terminals in the entire gray substance of the spinal cord. In the ventral root, after crushing, calcitonin gene-related peptide, chromogranin A, synapsin I, SV2, p38 and caligulin-like immunoreactivity accumulated in thick and medium-sized axons proximal to the crush, while only antisera against SV2 and p38 labelled accumulated material distal to the crush. In the sciatic nerve, the same essential picture was observed as in the ventral root, but here two other nervous components were also present in the normal sciatic nerve, i.e. peripheral branches of the sensory system and axons of the sympathetic system. By various denervation procedures, it was demonstrated that most calcitonin gene-related peptide-like immunoreactivity and almost all chromogranin A-like immunoreactivity, accumulating in thick axons proximally, emanated from the ventral root. Thin and medium-sized axons originated from the sensory and sympathetic systems and contributed to accumulations both proximally and distally to the crush. Synapsin I-like immunoreactive material accumulated only proximal to the crush, while SV2 and p38-like material accumulated bidirectionally in axons of all sizes. In motor endplates of the rat diaphragm and gastrocnemic muscle, no calcitonin gene-related peptide-like material was observed. However, some chromogranin A-like immunoreactivity was present, in addition to large amounts of synapsin I-like, p38-like and SV2-like material, which had a finely granular appearance and was concentrated near the presynaptic membrane of the nerve terminal endfeet, where synaptic vesicles are known to be located.

Animals↗
PubMedDate not supplied

Retardation in the slow axonal transport of cytoskeletal elements during maturation and aging.

Using the pulse-labeling method, the rate of the slow component (SC) of axonal transport was analyzed during maturation and aging. Ventral motor neurons and retinal ganglion cells of 3-, 6-, and 24-month-old Fischer 344 rats were radiolabeled with 35S-methionine. To measure the rates of SCa and SCb subcomponents, distributions of the total radiolabeled proteins and certain cytoskeletal proteins (actin, clathrin, tubulin, and the neurofilament proteins) were analyzed in the ventral root-sciatic nerve and optic nerve. Our results show that the rate of transport for both SCa and SCb proteins decreases with age in ventral motor axons and optic axons. For example, in ventral motor axons the rates of both SCa and SCb decreased 40% between 6 and 24 months. These results, with those of others, show that the rate of slow transport gradually decreases in the neurons of adult rats (7,11) The factors that may contribute to the slowing are discussed.

Aging↗
PubMed1998

A role for cyclin-dependent kinase(s) in the modulation of fast anterograde axonal transport: effects defined by olomoucine and the APC tumor suppressor protein.

Proteins that interact with both cytoskeletal and membrane components are candidates to modulate membrane trafficking. The tumor suppressor proteins neurofibromin (NF1) and adenomatous polyposis coli (APC) both bind to microtubules and interact with membrane-associated proteins. The effects of recombinant NF1 and APC fragments on vesicle motility were evaluated by measuring fast axonal transport along microtubules in axoplasm from squid giant axons. APC4 (amino acids 1034-2844) reduced only anterograde movements, whereas APC2 (aa 1034-2130) or APC3 (aa 2130-2844) reduced both anterograde and retrograde transport. NF1 had no effect on organelle movement in either direction. Because APC contains multiple cyclin-dependent kinase (CDK) consensus phosphorylation motifs, the kinase inhibitor olomoucine was examined. At concentrations in which olomoucine is specific for cyclin-dependent kinases (5 microM), it reduced only anterograde transport, whereas anterograde and retrograde movement were both affected at concentrations at which other kinases are inhibited as well (50 microM). Both anterograde and retrograde transport also were inhibited by histone H1 and KSPXK peptides, substrates for proline-directed kinases, including CDKs. Our data suggest that CDK-like axonal kinases modulate fast anterograde transport and that other axonal kinases may be involved in modulating retrograde transport. The specific effect of APC4 on anterograde transport suggests a model in which the binding of APC to microtubules may limit the activity of axonal CDK kinase or kinases in restricted domains, thereby affecting organelle transport.

Adenomatous Polyposis Coli↗
PubMed1978

Cerebellar afferent projections from the perihypoglossal nuclei: an experimental study with the method of retrograde axonal transport of horseradish peroxidase.

Details of cerebellar afferent projections from the perihypoglossal nuclei were studied in the cat by means of retrograde axonal transport of horseradish peroxidase (HRP). Labeled cells were observed bilaterally (with a preponderance ipsilaterally) in nuclei intercalatus and praepositus hypoglossi following injections in various folia of the entire vermis, paraflocculus, flocculus, fastigial nucleus, and the nucleus interpositus anterior and posterior. Relatively high densities of labeled cells were found in nucleus intercalatus following injections in the anterior part of the vermis, whereas labeled cells in nucleus praepositus hypoglossi were found more frequently following injections in the posterior part of the vermis. Labeled cells in the nucleus of Roller were found only following injections in the anterior lobe vermis, posterior vermal lobules VI and VII, in the flocculus and in the nucleus interpositus anterior. No labeled cells could be detected in the three subdivisions of the perihypoglossal nuclei following HRP injections in crus I, crus II, paramedian lobule, and lateral cerebellar nucleus. The distribution of the HRP positive cells indicated the presence of a topographically organized projection from certain regions of the perihypoglossal nuclei to different parts of the cerebellum. The afferent and efferent connections of the perihypoglossal nuclei in relation to a functional role in eye and head movements are discussed.

Afferent Pathways↗
PubMedDate not supplied

Acetylcholinesterase activity and its fast axonal transport in rabbit sciatic nerves during the recovery phase of experimental allergic neuritis.

Acetylcholinesterase (AChE) activity and its fast axonal transport were studied in rabbit sciatic nerves with a double ligature system during the recovery phase of experimental allergic neuritis (EAN), 6-9 days after the maximal symptoms, in order to obtain biochemical evidence of possible axonal damage in this primary demyelinating disease. The stationary AChE activity was significantly decreased, but the amount of the fast transported enzyme activity remained at the level of the controls. The velocity of the orthograde transport of AChE was slowed by about 15%, but this decrease was not statistically significant. Our results lend further support for the suggested neuronal damage in EAN, which can provide an explanation to the finding that the clinical symptoms in demyelinating diseases of the peripheral nervous system do not always correlate with the state of myelin.

Acetylcholinesterase↗
PubMed1975

Studies on the cerebellar projections from the main and external cuneate nuclei in the cat by means of retrograde axonal transport of horseradish peroxidase.

The cerebellar projections from the main and external cuneate nuclei in the cat have been studied by means of retrograde axonal transport of horseradish peroxidase. The main projection from the external cuneate nucleus (ECN) is to the intermediate and, possibly, the small lateral part of lobule V and to the paramedian lobule on the ipsilateral side. The projection from the ECN to the cerebellar regions mentioned is topographically organized. Cells in the caudal part of the ECN send their axons to the caudal parts of lobule V and to the rostral part of the paramedian lobule. Cells in the rostral part of the ECN project to the rostralmost part of lobule V and to the folia in the caudal part of the paramedian lobule. The experimental study also shows that cells in the main cuneate nucleus (MCN) send their axons to the cerebellum. These axons, like those from the ECN, terminate in the intermediate part of lobule V of the anterior lobe and in the paramedian lobule. However, the axons of the cells in the MCN terminate only in the superficial parts of the folia, whereas those from the ECN terminate in the depth of the folia in these two cerebellar areas. The present study also gives evidence that cells in the ventral part of the gracile nucleus send their axons to lobules I and II of the anterior lobe vermis. The observations referred to here are to our knowledge the first anatomical findings demonstrating a projection from the main cuneate and gracile nuclei onto the cerebellar cortex. The observations confirm previous physiological studies.

Animals↗