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Results for “Axonal Transport”

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At least 955 records · Page 53Linked to original sources
PubMed1978

Effect of diphtheritic demyelination on axonal transport in the sciatic nerve and subsequent muscle changes in the chicken.

Chicken sciatic nerves undergo demyelination following intraneural injection of diphtheria toxin and subsequent atrophy of some muscular cells. Paresis occurs after one week and lasts approximately three weeks; at the height of the lesion C14-leucine was injected into the ventral horn cells of the spinal cord. The axonal transport of fast flowing labelled proteins was followed down the sciatic nerve axons and flow rates at two different times were measured. Muscle cells were stained for succinic dehydrogenase and ATPase; fibre diameters, total protein, and total radioactivity associated with the nerves were also measured. The results showed that the fast flowing labelled proteins accumulated at the demyelination site while the muscle cells supplied by these nerves showed reduction of fibre diameter and evidence of degeneration. Further studies are in progress on slow moving proteins and muscle cells.

Animals↗
PubMed2004

Oligodendroglial modulation of fast axonal transport in a mouse model of hereditary spastic paraplegia.

Oligodendrocytes are critical for the development of the plasma membrane and cytoskeleton of the axon. In this paper, we show that fast axonal transport is also dependent on the oligodendrocyte. Using a mouse model of hereditary spastic paraplegia type 2 due to a null mutation of the myelin Plp gene, we find a progressive impairment in fast retrograde and anterograde transport. Increased levels of retrograde motor protein subunits are associated with accumulation of membranous organelles distal to nodal complexes. Using cell transplantation, we show categorically that the axonal phenotype is related to the presence of the overlying Plp null myelin. Our data demonstrate a novel role for oligodendrocytes in the local regulation of axonal function and have implications for the axonal loss associated with secondary progressive multiple sclerosis.

Alleles↗
PubMed2006

Reversible disruption of dynactin 1-mediated retrograde axonal transport in polyglutamine-induced motor neuron degeneration.

Spinal and bulbar muscular atrophy (SBMA) is a hereditary neurodegenerative disease caused by an expansion of a trinucleotide CAG repeat encoding the polyglutamine tract in the androgen receptor (AR) gene. To elucidate the pathogenesis of polyglutamine-mediated motor neuron dysfunction, we investigated histopathological and biological alterations in a transgenic mouse model of SBMA carrying human pathogenic AR. In affected mice, neurofilaments and synaptophysin accumulated at the distal motor axon. A similar intramuscular accumulation of neurofilament was detected in the skeletal muscle of SBMA patients. Fluoro-gold labeling and sciatic nerve ligation demonstrated an impaired retrograde axonal transport in the transgenic mice. The mRNA level of dynactin 1, an axon motor for retrograde transport, was significantly reduced in the SBMA mice resulting from pathogenic AR-induced transcriptional dysregulation. These pathological events were observed before the onset of neurological symptoms, but were reversed by castration, which prevents nuclear accumulation of pathogenic AR. Overexpression of dynactin 1 mitigated neuronal toxicity of the pathogenic AR in a cell culture model of SBMA. These observations indicate that polyglutamine-dependent transcriptional dysregulation of dynactin 1 plays a crucial role in the reversible neuronal dysfunction in the early stage of SBMA.

Analysis of Variance↗
PubMed2001

Impaired retrograde axonal transport of adenovirus-mediated E. coli LacZ gene in the mice carrying mutant SOD1 gene.

A replication-defective recombinant adenoviral vector containing E. coli lacZ gene was injected into the gastrocnemius muscles of transgenic mice carrying mutant Cu/Zn superoxide dismutase (SOD1) gene and non-transgenic wild-type mice at 40 weeks of age. After 60 and 90 h of the injection, lacZ staining was observed at the distal ends of the sciatic nerves in both mice groups, with the number and the distances greatly reduced in the transgenic mice. Mean velocities of retrograde transport for lacZ was estimated to be 2.1 and 0.05 mm/24 h in non-transgenic and transgenic mice, respectively. These results indicate that the retrograde axonal transport of foreign gene product is impaired in the mice model for familial amyotrophic lateral sclerosis.

Adenoviridae↗
PubMed2001

Rabies virus glycoprotein pseudotyping of lentiviral vectors enables retrograde axonal transport and access to the nervous system after peripheral delivery.

In this report it is demonstrated for the first time that rabies-G envelope of the rabies virus is sufficient to confer retrograde axonal transport to a heterologous virus/vector. After delivery of rabies-G pseudotyped equine infectious anaemia virus (EIAV) based vectors encoding a marker gene to the rat striatum, neurons in regions distal from but projecting to the injection site, such as the dopaminergic neurons of the substantia nigra pars compacta, become transduced. This retrograde transport to appropriate distal neurons was also demonstrated after delivery to substantia nigra, hippocampus and spinal cord and did not occur when vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped vectors were delivered to these sites. In addition, peripheral administration of rabies-G pseudotyped vectors to the rat gastrocnemius muscle leads to gene transfer in motoneurons of lumbar spinal cord. In contrast the same vector pseudotyped with VSV-G transduced muscle cells surrounding the injection site, but did not result in expression in any cells in the spinal cord. Long-term expression was observed after gene transfer in the nervous system and a minimal immune response which, together with the possibility of non-invasive administration, greatly extends the utility of lentiviral vectors for gene therapy of human neurological disease.

Animals↗
PubMed1991

Axonal transport kinetics and posttranslational modification of synapsin I in mouse retinal ganglion cells.

Synapsin I is a neuron-specific phosphoprotein primarily localized at the presynaptic terminals, where it is thought to play an important role in the mechanisms involved in neurotransmitter release. Its interaction with cytoskeletal proteins and with small synaptic vesicles is regulated in vitro by phosphorylation by a calcium/calmodulin-dependent kinase. Here, we present the first evidence that, in the mouse retinal ganglion cells, synapsin I, moving along the axon with the slow component of axonal transport, is phosphorylated in vivo at both the head and tail regions. In addition, our data suggest that, after synapsin I has reached the nerve endings, the relative proportion of differently phosphorylated molecules of synapsin I changes, and that these changes lead to a decrease of the overall content of phosphorus. The more basic forms, here collectively referred to as beta-forms, become predominant at the terminals after 7 d postlabeling, when the bulk of transported synapsin I has entered the superior colliculus. Along the axon, phosphorylation could be functional in preventing synapsin I from forming, with actin, a dense meshwork that would restrict organelle movement. On the other hand, at the terminals, the dephosphorylation-phosphorylation of synapsin I may regulate the clustering of small synaptic vesicles and modulate neurotransmitter release by controlling the availability of small synaptic vesicles for exocytosis.

Animals↗
PubMed1976

Projection of thalamic neurons to cat primary vestibular cortical fields studied by means of retrograde axonal transport of horseradish peroxidase.

The two vestibular cortical projection areas in the anterior suprasylvian sulcus and post-cruciate dimple regions were defined by evoked potential technique in anaesthetized cats. The thalamic location of neurons with axon terminals in these fields was determined using the method of retrograde axonal transport of horseradish peroxidase. The ascending vestibular pathway appeared to be separated also at the thalamic level, where cells in the ventroposterolateral nucleus were found to project to the post cruciate dimple and cells in the posterior nuclear group to the anterior suprasylvian vestibular cortical fields.

Afferent Pathways↗
PubMed1988

Orthograde and retrograde axonal transport in the regenerating frog sciatic nerve show different sensitivities to vanadate.

The outgrowth region of the regenerating frog sciatic nerve shows an increased permeability for various drugs. The present experiments indicate that this is also true for vanadate, a substance of special interest in relation to axonal transport. Six days after a bilateral crush lesion, the sciatic nerves, including the spinal ganglia, were incubated in a compartmented chamber. Orthograde transport was assessed from the distribution and the accumulation of [3H]leucine-labelled proteins in the nerve growth region. Retrograde transport was examined by allowing orthogradely transported labelled materials to reverse at the regenerating region and then to accumulate at a ligature during a second incubation period. Vanadate at 0.5 mM and higher concentrations was found to inhibit orthograde and retrograde transport in the outgrowth region (6 mm long at 6 d after crush), whereas 0.2 mM vanadate inhibited transport only in the retrograde direction. The observations lend further support to the idea that the mechanisms of transport in the two directions are different.

Animals↗
PubMed1994

Defective activity of Na+,K(+)-ATPase in peripheral nerve of diabetic rats is independent of the axonal transport of the enzyme.

This study addressed the question as to whether the reduced activity of Na+,K(+)-ATPase reported to occur in diabetic nerves and to play a crucial role in the pathogenesis of diabetic neuropathy could be due to derangements in the axonal transport of the enzyme. A micromethod was developed to evaluate the ATPase accumulation in individual segments of ligated sciatic nerves from streptozotocin-induced diabetic rats. The results confirmed a approximately 40% decrease in the background activity, but showed that the enzyme was transported at similar rates in both anterograde and retrograde directions, suggesting that the decrease in its activity does not depend on an altered delivery along the axons.

Analysis of Variance↗
PubMed1980

Effects of proton irradiation of the lumbar intumescence on intra-axonal transport of acetylcholine and cholinergic enzymes in rat sciatic nerve.

The content and intra-axonal transport of acetylcholine (ACh) and the cholinergic enzymes cholineacetyltransferase (CAT) and ACh-esterase (AChE) in sciatic nerve were investigated in rats following single dose proton irradiation of the lumbar intumescence of the spinal cord with 60 Gy or 200 Gy. One, 7 or 30 days after irradiation nerve-crush operations were performed 12 hours before killing and the levels of ACh and enzyme activities in nerve segments relative to the crushes were estimated by biologic (ACh) or chemical (enzyme) methods. The results indicate that alterations in intraneuronal dynamics of ACh and related enzymes are not a major cause for the development of neurologic symptoms of the motor system after irradiation, and that descending myelinated axons are of minor importance for the regulation of cholinergic substances in rat motor nerves.

Acetylcholine↗
PubMed1989

Modification of the microtubule-binding and ATPase activities of kinesin by N-ethylmaleimide (NEM) suggests a role for sulfhydryls in fast axonal transport.

N-Ethylmaleimide, an agent which alkylates free sulfhydryls in proteins, has been used to probe the role of sulfhydryls in kinesin, a motor protein for the movement of membrane-bounded organelles in fast axonal transport. When squid axoplasm is perfused with concentrations of NEM higher than 0.5 mM, organelle movements in both the anterograde and retrograde directions cease, and the vesicles remain attached to microtubules. Incubation of highly purified bovine brain kinesin with similar concentrations of NEM modifies the enzyme's microtubule-stimulated ATPase activity and promotes the binding of kinesin to microtubules in the presence of ATP. These results suggest that alkylation of sulfhydryls on kinesin alters the conformation of the protein in a manner that profoundly affects its interactions with ATP and microtubules. The NEM-sensitive sulfhydryls, therefore, may provide a valuable tool for the dissection of functional domains of the kinesin molecule and for understanding the mechanochemical cycle of this enzyme.

Adenosine Triphosphatases↗
PubMed1986

Neurotoxicity of halogenated phenylacetylureas is linked to abnormal onset of rapid axonal transport.

A structure-activity study was performed to investigate the mechanism of neurotoxicity induced in rats by treatment with p-bromophenylacetylurea (BPAU). Phenylacetylurea and 7 derivatives were tested for their ability to induce hindlimb weakness after twice weekly administration in doses of 200 mg/kg, up to a cumulative maximum of 2000 mg/kg. In this test, BPAU and its chloro- analog were about equipotent, but none of the other analogs displayed any evidence of neurotoxicity. Since BPAU toxicity was believed to involve abnormalities in rapid axonal transport, selected analogs were examined in a transport experiment. None of the compounds led to alterations in the maximal rate of rapid anterograde transport, as measured after intraspinal injections of [35S]methionine in rats treated with 400 mg/kg of toxicant, 7 days earlier. However, both BPAU and its chloro- analog caused marked shortening of the delay between isotope injection and transport onset, an effect not seen with either of the two non-neurotoxic analogs tested. It is hypothesized that the accelerated transport onset is a key step in development of the neuropathy, possibly causing organelle abnormalities that interfere with turnaround and recirculation of transported particles.

Animals↗
PubMed1985

Reversal of deficits in axonal transport and nerve conduction velocity by treatment of streptozotocin-diabetic rats with myo-inositol.

This study examined the effects of myo-inositol treatment on the deficits of motor nerve conduction velocity and of axonal transport of choline acetyltransferase in rats with streptozotocin-induced diabetes. Motor nerve conduction velocity was measured in seven groups of male rats. Two groups formed nondiabetic controls; one survived for 3 and the other for 6 weeks, then motor nerve conduction velocity was again measured and the accumulation of choline acetyltransferase activity proximal to a 24-h sciatic nerve constriction was estimated. The other five groups were rendered diabetic and subjected to similar measurements. Two diabetic groups were untreated and survived 3 or 6 weeks. The other three groups received myo-inositol for 1, 2, and 3 weeks, respectively, commencing 21 days after induction of diabetes. These groups survived for 4, 5, or 6 weeks, respectively. In all groups surviving for longer than 3 weeks an interim measurement of motor nerve conduction velocity was made 21 days after the start of the experiment (immediately before onset of treatment in the treated groups). In these groups a third measurement was made on the day before death. At death, choline acetyltransferase accumulation was measured and the remainder of the sciatic nerves was assayed for sorbitol and myo-inositol. In the two untreated diabetic groups we found reduced motor nerve conduction velocity, a deficit in the accumulation of choline acetyltransferase proximal to the sciatic nerve constriction, and a marked build-up of nerve sorbitol and a depletion of nerve myo-inositol. All three treated groups showed a reversal of this myo-inositol depletion without a reduction in the nerve sorbitol content.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed2003

Axonal transport and sorting of herpes simplex virus components in a mature mouse visual system.

The time course for delivery and transport of two major proteins of herpes simplex virus (HSV) has been determined for mature mouse retinal ganglion cell axons in vivo. Twenty-four hours after intravitreal injection of HSV, valacyclovir was introduced into the drinking water of the mice to inhibit subsequent viral replication. Without treatment, viral spread and replication in periaxonal glial cells confound study of axonal transport. At 2 to 5 days after infection, the animals were sacrificed and contiguous segments of the optic pathway were removed. Immunofluorescence microscopy indicated that the number of infected astrocytes was reduced in the proximal optic nerve and eliminated in the optic tract. Western blots of the retina with antibodies for envelope and capsid components, glycoprotein D (gD) and VP5, respectively, revealed that both components were expressed in retinal homogenates by 2 days. Results of reverse transcription-PCR indicated that there was no gD mRNA present in the treated optic tract 5 days after infection. Therefore, we conclude that gD is transcribed from viral mRNA in the retinal ganglion cell bodies. The gD accumulated in the proximal ganglion cell axon by 2 days and reached the most distal segment after 3 days. The VP5 first appeared in the proximal axons at 4 days, about 48 h after the appearance of gD. Thus, gD entered the axon earlier and independent of VP5. These finding confirm the subassembly model of viral transport in neurons and suggest that there is a 4- to 5-day window for initiation of effective antiviral treatment with valacyclovir.

Acyclovir↗
PubMed1977

Neurophysin biosynthesis: conversion of a putative precursor during axonal transport.

[35S]Cysteine injected adjacent to the supraoptic nucleus of the rat is rapidly incorporated into a 20,000-dalton protein that, in time, is converted to a 12,000-dalton labeled protein, neurophysin. This putative precursor of neurophysin appears to be synthesized in the supraoptic nucleus and transformed to neurophysin and related peptides during axonal transport to the neurohypophysis.

Animals↗
PubMed1978

Substances moved by axonal transport and released by nerve stimulation have an innervation-like effect on muscle.

Substances which have an innervation-like effect on the cholinesterase activity of organ-cultured rat extensor digitorum longus muscles are moved in nerve by axonal transport, are released from nerve by stimulation, and are present in innervated muscle but apparently absent from denervated muscle. Substances which increase the acetylcholine sensitivity of cultured muscles behave similarly.

Acetylcholine↗
PubMed1987

Intraneuronal IgG in the central nervous system: uptake by retrograde axonal transport.

The uptake of immunoglobins by CNS neurons was studied in rats. Rats were injected IP with solutions containing large amounts of rabbit IgG. Immunocytochemical staining of sections of the neuraxis revealed uptake of rabbit IgG by motor neurons of the CNS with axons projecting outside of the blood-brain barrier, including ventral horn motor neurons and cranial nerve motor nuclei neurons as well as in neurons projecting to the hypothalamus and area postrema. Staining was also noted in certain large neurons of the reticular formation and in Purkinje cells, as well as diffusely in the hypothalamus, area postrema, the pia mater, and associated vasculature and larger penetrating vessels. Uptake of rabbit IgG by lumbar spinal cord motor neurons projecting to the sciatic nerve was prevented by ligation of the sciatic nerve. These experiments support the hypothesis that certain central neurons take up immunoglobins from the periphery by retrograde axonal transport. The function of this process is not known, but it may have significance for the pathogenesis of motor and autonomic neuropathies and neuronopathies.

Animals↗