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At least 343 records · Page 19Linked to original sources
PubMed1986

Graded inhibition of retrograde axonal transport by compression of rabbit vagus nerve.

Effects of experimental compression at different pressures on retrograde axonal transport were studied in rabbit vagus nerve. Proteins in the sensory neurones were radiolabelled by injection of [3H]leucine into the nodose ganglion. Sixteen hours after labelling, a small compression chamber and/or ligatures were applied around the cervical part of the vagus nerve for 8 h. Compression of the vagus nerve at 20, 30 and 200 mm Hg pressure induced a graded inhibition of both retrograde and anterograde transport of the radiolabelled proteins. Neither retrograde nor anterograde transport was affected by the presence of the non-inflated chamber. The results indicate that compression at pressures similar to those found in human carpal tunnel syndrome can block retrograde axonal transport. The consequences of inhibition of retrograde and anterograde axonal transport for the metabolism in the nerve cell bodies are discussed.

Air Pressure↗
PubMed1993

MR imaging of slow axonal transport in vivo.

Three magnetopharmaceuticals based on a monocrystalline iron oxide nanocompound (MION) are evaluated as potential contrast agents for demonstrating axonal transport in vivo by magnetic resonance (MR) imaging. One agent has a strong positive charge, one has a strong negative charge, and the third is covalently linked to wheat germ agglutinin, a plant lectin with a high affinity for axon terminals. All three agents were tagged with rhodamine, and fluorescence microscopy was used to determine their fate after administration and to validate the imaging results. Following injection into or near various neural structures in the motor and visual systems of rats, MR images were obtained at multiple times up to 11 days later, and the imaged tissues were processed for subsequent histological examination. Similar results were obtained with all three agents. Axonal transport was not seen by MR imaging or fluorescence microscopy when the agents were injected into the calf muscles, the vitreous of the eye, or the superior colliculus. However, bidirectional axonal transport was shown unequivocally by both methods after injection directly into the site of a focal crush injury to the sciatic nerve. The nerve, which otherwise is isointense with surrounding tissues on MR images, appeared as a uniformly hypointense structure having a length approximately in proportion to the time from injection to imaging. By 11 days, the course of the nerve was traceable from its component roots in the cauda equina to its bifurcation into the tibial and common peroneal nerves in the leg. A transport rate of about 5 mm/day was calculated, which is consistent with the mechanism of slow transport. MION-based magnetopharmaceuticals thus can be used to demonstrate slow axonal transport, and thereby visualize peripheral nerves, in vivo by MR imaging.

Animals↗
PubMed1986

beta,beta'-Iminodipropionitrile impairs retrograde axonal transport.

beta,beta'-Iminodipropionitrile (IDPN), a neurotoxin, causes redistribution of neurofilaments in axons followed by the development of proximal axonal swellings and, in chronic intoxication, a distal decrease in axonal caliber. The latter changes are caused by a selective impairment in the slow anterograde axonal transport of neurofilament proteins. To assess the role of retrograde axonal transport in IDPN toxicity, we used [3H]N-succinimidyl propionate ([3H]NSP) to label covalently endogenous axonal proteins in sciatic nerve of the rat and measured the accumulation of radioactively labeled proteins in the cell bodies of motor and sensory neurons over time. IDPN was injected intraneurally 6 h or intraperitoneally 1 day before subepineurial injection of [3H]NSP into the sciatic nerve, and the animals were killed 1, 2, and 7 days after [3H]NSP injection. Neurotoxicity was assessed by electron microscopic observation of the nerves of similarly treated animals. Both intraneural and intraperitoneal injection of IDPN caused an acute reduction in the amount of labeled proteins transported back to the cell bodies. The early appearance of these changes suggests that alterations in retrograde transport may play a role in the production of the neuropathic changes.

Animals↗
PubMed1977

Axonal transport of putrescine, spermidine and spermine in normal and regenerating goldfish optic nerves.

Radopactove putrescine, spermidine or spermine was injected into the right eye of normal goldfish and fish in which both optic nerves had been crushed 18 days earlier. Fish were sacrificed 0.25-21 days after injection. Trichloroacetic acid-soluble and -insoluble material was extracted from the right retina and both tecta and assayed for radioactivity (significant differences between left and right tecta suggesting axonal transport). The nature of the radioactivity in the TCA-soluble fraction was determined on an amino acid analyzer. Results indicate that putrescine is not axonally transported in intact goldfish optic nerves, but that during regeneration of the optic nerve large amounts of putrescine are axonally transported at rates similar to the fast component of protein transport. Spermidine appears to be axonally transported both in intact optic nerves and in regenerating optic nerves, and at an intermediate rate of transport; the amount of spermidine transported is significantly increased during regeneration. Spermine is also axonally transported in intact and regenerating nerves, at a rate similar to the rapid rate of protein transport. The amount of spermine transported appears to be slightly less in regenerating than in intact nerves during early stages of regeneration, but increases during later stages of nerve regeneration. The results suggest that putrescine and spermidine may be preferentially transported during nerve regeneration, while spermine and spermidine are transported extensively in intact nerves.

Animals↗
PubMed1978

Slow axonal transport of neurofilament proteins: impairment of beta,beta'-iminodipropionitrile administration.

beta,beta'-Iminodipropionitrile (IDPN) administration prevented normal slow axonal transport of [35S]methionine- or [3H]leucine-labeled proteins in rat sciatic motor axons. Ultrastructural and electrophoretic studies showed that the neurofilament triplet proteins in particular were retained within the initial 5 millimeters of the axons, resulting in neurofilament-filled axonal swellings. Fast anterograde and retrograde axonal transport were not affected. The IDPN thus selectively impaired slow axonal transport. The neurofibrillary pathology in this model is the result of the defective slow transport of neurofilaments.

Axonal Transport↗
PubMed1989

Axonal transport reductions in acute experimental allergic encephalomyelitis: qualitative analysis of the optic nerve.

In order to determine if changes in axonal transport were different in adult animals with acute experimental allergic encephalomyelitis (EAE), in comparison to juvenile animals with chronic EAE, the effects of this acute demyelinating disorder on axonal transport were examined in the optic nerves of adult strain-13 guinea pigs. Utilizing autoradiographic analysis of silver grain counts, both the fast and slow components of orthograde transport were studied at intervals of thirty minutes, three hours, one day and three days after tritiated leucine injection into the vitreous cavity. In order to determine the contribution of fiber loss in acute EAE, optic nerve fiber density was analyzed from electron micrographs of normal and demyelinated nerves. Animals with acute EAE had a decrease in radioactivity at the lamina retinalis and lamina choroidalis after thirty minutes and three hours, and at the lamina scleralis and foci of demyelination after one and three days. A 16% loss of fibers did not account for as much as a 74% reduction in radioactivity with acute EAE. The global reductions in axonal transport observed in acute EAE animals may contribute to their progressive deterioration and eventual demise by lack of delivery of tubulo-vesicular materials for synaptic transmission, axolemmal proteins for electrogenesis and neurofilamentary components of the cytoskeleton. Moreover, they are unlike the increase of fast axonal transport associated with recovery of physiologic function characteristic of animals with the chronic form of the disease.

Animals↗
PubMed1983

Early and dose-dependent decrease of retrograde axonal transport in acrylamide-intoxicated rats.

The effect of retrograde axonal transport of doses of acrylamide ranging from 50 to 500 mg/kg was studied in sensory nerve of rats. Accumulation of trichloroacetic acid-phosphotungstic acid-insoluble label was measured in a collection segment distal to a double ligature placed on the sciatic nerve at intervals 9-15 h and 9-24 h following injection into the dorsal root ganglion of the fifth lumbar root of [35S]methionine and [3H]fucose. After a dose of 100 mg/kg of acrylamide no neurological signs of neuropathy had yet appeared, but retrograde buildup of protein label was significantly reduced for the long interval (2.20 +/- 0.49 arbitrary units (AU) (mean +/- SD) versus 2.81 +/- 0.57 AU in controls, 2p = 0.034). No abnormality of the short interval appeared before a dose of 500 mg/kg was reached. The retrograde transport abnormality was dose-related (r = -0.85, n = 28, and 2p = 1.2 x 10(-8)), as was the degree of neuropathy evaluated by "blind" neurological scoring (r = 0.88, n = 14, and 2p = 2.8 x 10(-5)). After a dose of 500 mg/kg, when the rats were severely disabled with almost total incoordination of the hindlegs, the retrograde accumulation of the long interval was profoundly depressed (1.08 +/- 0.28 AU versus 2.81 +/- 0.57 AU in controls, 2p = 1.2 x 10(-7)). Similar changes were seen in accumulation of glycoprotein label. After the rats had recovered for 4-10 weeks neurological signs of neuropathy had disappeared and the transport abnormality had improved. To test the specificity of acrylamide on the retrograde transport defect N-hydroxymethylacrylamide and methylene-bisacrylamide, which do not induce neuropathy, were studied. None of these related compounds influenced the transport. These observations imply that in acrylamide intoxication a defect in the amount of material carried by retrograde axonal transport rather than in "turnaround" time or in transport velocity is present, that the transport abnormality precedes the development of neuropathy, and that it is related to the degree of the neurological disability. We suggest that the retention of protein in the distal axons in the functional counterpart of the well-known accumulation of vesicular organelles in the preterminals.

Acrylamide↗
PubMed1979

Axonal transport in early experimental diabetes.

In the present study fast axonal transport was examined in streptozotocin rats with 4 weeks duration in diabetes. Tritiated leucine and 14C-labelled glucosamine were injected into the fifth lumbar ganglion and TCA-soluble as well as insoluble activity were measured in segments of the sciatic nerve at various time intervals. (1) Time from injection until start of fast axonal transport was prolonged in diabetic rats whereas anterograde transport velocity was unchanged. (2) Incorporation of labelled leucine was reduced by 40%, whereas labelled glucosamine incorporation was unchanged. (3) Alterations observed in accumulations of labelled glycoconjugates proximal and distal to a collection crush might represent a decreased amount of retrograde transported material. The changes found in protein and glycoconjugate synthesis and transport could be related to the early reduction in axon calibre and conduction velocity in peripheral nerve of streptozotocin-diabetic rat.

Animals↗
PubMed2003

Does neurofilament phosphorylation regulate axonal transport?

Phosphorylation of neurofilaments has long been considered to regulate their axonal transport rate and, in doing so, to provide stability to mature axons. Interpretation of data recently obtained following C-terminal deletion experiments has prompted a challenge to this hypothesis. We present evidence that these deletion studies remain consistent with, rather than refute, a role for C-terminal phosphorylation in regulation of neurofilament axonal transport.

Amino Acid Sequence↗
PubMed1975

Slow axonal transport or proteins; blockade by interruption of contact between cell body and axon.

The influence of ligation and colchicine treatment on the axonal transport of slowly migrating [3H]leucine-labelled proteins was studied in the vagus nerve of the rabbit. Two days after [3H]leucine labelling of the dorsal motor nucleus of the vagus nerve, ligation or local application of 60 mM colchicine immediately blocked the further progression of slowly migrating proteins distal to the site of treatment. Application of 50-100 mug colchicine to the nerve cell bodies 2 days after labelling blocked the transport of slowly migrating proteins within the next 24 h. It is suggested that contact between nerve cell body and the axon is necessary for the maintenance of the slow transport of proteins in these nerves.

Animals↗
PubMed1982

Recovery of fast axonal transport and retinal protein synthesis in the rabbits after intraocular administration of vinblastine.

Orthograde fast axonal transport was almost completely blocked one day after the intraocular injection of 10-100 micrograms of vinblastine (VLB), then recovered gradually for up to 2 months. Recovery was not complete, however; there was a definite relationship between the dose of VLB administered and the degree of recovery of fast axonal transport. Retinal protein synthesis was reduced by intraocular VLB, but there was no relationship between the dose administered and the amount of reduction of protein synthesis. Cytotoxicity of VLB to the retina is less probable. The participation of retrograde axonal transport in the metabolism of cell bodies is discussed.

Afferent Pathways↗
PubMed1985

Blockage at two points of axonal transport in glaucomatous eyes.

Blockage of axonal protein transport in intraocular hypertensive primates (Macaca irus) was studied autoradiographically and quantitatively and the findings compared with our previous work on rabbits. Fast axonal transport was blocked at two points, at the lamina scleralis and at the edge of posterior scleral foramen, and reduced by 25% when intraocular pressure of 50 mmHg continued for 6 h. The importance of the blockage at the lamina scleralis and at the edge of scleral foramen for the explanation of paracentral scotomas and the peripheral nasal step (Rønne) is discussed.

Animals↗
PubMed1981

Electrophoretic analysis of axonally transported proteins in toad retinal ganglion cells.

As a preliminary step to studying changes in axonal transport in regenerating neurons, we have analyzed the composition and organization of polypeptides normally axonally transported in a neuronal system capable of regeneration, i.e., the retinal ganglion cells of the toad, Bufo marinus. We labeled proteins synthesized in the retina with 35S-methionine and subsequently used one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis to analyze labeled, transported proteins in tissues containing segments of the axons (the optic nerve, optic tract, and optic tecta) of the retinal ganglion cells. The transported polypeptides could be divided into five groups according to their apparent transport velocities. Many of the polypeptides of each group were electrophoretically similar to polypeptides of corresponding groups previously described in rabbit and guinea pig retinal ganglion cells, and in some cases, additional properties of the polypeptides indicated that the transported materials of the two vertebrate classes were homologous. These results serve two purposes. First they establish the retinal ganglion cells of the toad Bufo marinus as a model system in which changes in gene expression related to regeneration may be studied. Second they show that the organization and many aspects of the composition of axonal transport in retinal ganglion cells have been conserved in animals as unrelated as amphibians, and mammals.

Animals↗
PubMed1986

Inhibition of fast axonal transport in bullfrog nerves by dibenzazepine and dibenzocycloheptadiene calmodulin inhibitors.

The effects of the calmodulin inhibitors amitriptyline, desipramine, imipramine, and clomipramine on fast axonal transport, oxidative metabolism, and density of axonal microtubules were measured in bullfrog spinal nerves in vitro. The four drugs tested inhibited the fast orthograde transport of [3H]leucine-labelled proteins and the fast retrograde transport of acetylcholinesterase at a concentration of 0.2 mM. Amitriptyline, desipramine, and imipramine were equipotent inhibitors of transport, and clomipramine was a more potent inhibitor than imipramine. The adenosine triphosphate content of the nerves was reduced by at most 19% by the compounds under study; such a reduction cannot account for the inhibition of fast axonal transport. Desipramine and imipramine had no significant effect on the density of microtubules in unmyelinated axons, whereas amitriptyline only reduced it by 18%; the inhibition of axonal transport by these three drugs can therefore not be explained by microtubule disruption. Clomipramine reduced microtubular density by 40%, and this effect may have contributed to the inhibition of fast axonal transport. The inhibition of fast axonal transport by desipramine, imipramine, and amitriptyline may be related to the inhibition of calmodulin function by these drugs. The similar potency of these three drugs as inhibitors of fast axonal transport goes in parallel with their known similar potency as calmodulin antagonists.

Acetylcholinesterase↗
PubMed1992

Fast axonal transport is modulated by altering trans-axolemmal calcium flux.

Factors involved in fast axonal transport (motor proteins, microtubules, organelles, etc.) have been identified but the molecular mechanism controlling transport is unknown. We used video enhanced microscopy to directly evaluate the effect of calcium on fast axonal transport (FAxT). FAxT alterations included rapid speed decreases (within minutes) in Ca2+ free buffer and rapid speed increases (within seconds) when axons were treated with parathyroid hormone, BAY K 8644, or K+ depolarization. The speed increases were blocked by dihydropyridine Ca2+ channel antagonists. Ryanodine (20 microM), known to block calcium release from subcellular stores, caused a decrease in the rate of retrograde FAxT. Calcium ionophore A23187 (at 1 and 20 micrograms/ml) caused increases in FAxT, an effect also noted only in retrograde moving organelle traffic. Hyper- or hypo-tonic solutions produced no alterations making axoplasmic viscosity changes an unlikely explanation for the speed changes. Reproducible alteration of FAxT by manipulation of Ca2+ levels provides evidence that Ca2+ modulates fast axonal transport. Retrograde transport appears more sensitive to changes in Ca2+ and differential effects on antero- and retro-FAxT mechanisms suggest directional specificity for some of these signals which may be based upon the organelle size. Endogenous substances (e.g. PTH) that trigger axonal Ca2+ changes may rapidly modulate the rate of material delivery in axons. The results are discussed within the context of a Ca2+/calmodulin-dependent modification of the cytoskeletal matrix.

Animals↗
PubMed1996

Visualization of slow axonal transport in vivo.

In axons, cytoskeletal constituents move by slow transport. However, it remains controversial whether axonal neurofilaments are dynamic structures in which only subunits are transported or whether filaments assemble in the proximal axon and are transported intact as polymers to the axon terminus. To investigate the form neurofilament proteins take during transport, neurons of transgenic mice lacking axonal neurofilaments were infected with a recombinant adenoviral vector encoding epitope-tagged neurofilament M. Confocal and electron microscopy revealed that the virally encoded neurofilament M was transported in unpolymerized form along axonal microtubules. Thus, neurofilament proteins are probably transported as subunits or small oligomers along microtubules, which are major routes for slow axonal transport.

Adenoviridae↗
PubMed1984

[Non-quantum release of acetylcholine from motor nerve endings and denervation changes in muscle fiber membranes in the rat following blockade of axonal transport].

On the 5th day after blockade of axonal transport with colchicine in rat the resting potential of diaphragm muscle fibre decreased, input resistance increased and the difference between postsynaptic and extrasynaptic membrane in this respect disappeared; extrasynaptic sensitivity to acetylcholine, anode breakdown and tetrodotoxin-resistant action potentials appeared almost in the same form as after nerve section. Application of colchicine to motor nerve, in contrast to nerve section, did not disrupt quantal and non-quantal acetylcholine secretion in motor nerve endings and did not stop muscle contractile activity. The size of non-quantal acetylcholine secretion was estimated by the amplitude of muscle membrane hyperpolarisation in the presence of curare in solution after preliminary acetylcholinesterase inhibition with armin. The data confirm the suggestion that the neurotrophic control of skeletal muscle fibre membrane in mammals is carried out by substances transported to muscle by axonal flow with participation of impulse activity. Synaptic acetylcholine secretion from motor nerve endings in non-quantal form does not play a marked role in neurotrophic control of muscle fibre membrane.

Acetylcholine↗