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At least 829 records · Page 46Linked to original sources
PubMed1988

Effects of kainic acid lesions in lateral geniculate nucleus: activity dependence of retrograde axonal transport of fluorescent dyes.

Kainic acid lesions in the dorsal lateral geniculate nucleus of rats block the retrograde axonal transport of fluorescent dyes in corticogeniculate neurons without affecting the retrograde transport of D-aspartate or the orthograde transport of radiolabelled proteins in these neurons. This blocking of dye transport does not appear to be a consequence of kainic acid-induced damage to axon terminals in the geniculate since retinal ganglion cells are still able to transport dyes retrograde. A more likely explanation for these results is that fluorescent dye transport requires electrical activity in neurons, and elimination of the geniculate afferents to visual cortex reduces impulse traffic in cortical output fibers to a level below that required to support detectable dye transport. This interpretation is supported by the observation that kainic acid lesions also reduce retrograde transport of dyes in cortical neurons which project to the superior colliculus. Electrical stimulation in the subcortical white matter restores the transport of dye compounds in corticogeniculate neurons: evidence consistent with an activity-dependent mechanism of retrograde transport for these substances. These results provide evidence that axon terminals of retinal ganglion cells and corticogeniculate neurons survive in kainate-lesioned geniculates and are capable of normal neuronal function.

Amidines↗
PubMed1982

Neural pathways to lower urinary tract identified by retrograde axonal transport of horseradish peroxidase.

A new technique for tracing nerve fibers supplying specific organs by retrograde axonal transport of the enzyme horseradish peroxidase (HRP) was used to determine the innervation of various segments of the lower urinary tract. HRP was injected at the level of the bladder neck, postprostatic urethral segment, pelvic nerve, pudendal nerve, and pelvic floor musculature to determine precise nerve supply to each site, as well as possible overlap. The technique determines the exact spinal level of innervation, as well as the number of nuclei directly related to the motor neuron axons supplying innervation to each particular site. Representation of these nuclei at various levels of the spinal cord was shown in various serial sections obtained after the injection of HRP. This technique is accurate and precise; it is valuable in establishing exact neural anatomic connections between the central nervous system and target organs.

Anal Canal↗
PubMed1985

Quantitative autoradiographic evidence for axonal transport of imipramine receptors in the central nervous system of the rat.

Interruption of the ascending serotonin axons of the medial forebrain bundle (MFB) in the rat brain produced a progressive time-dependent accumulation of imipramine receptors (labeled for autoradiography with [3H]imipramine). The largest accumulation of receptors occurred during the first 12 h at the caudal aspect of the lesion. An electrolytic lesion of the nucleus raphe dorsalis, administered 24 h prior to interruption of the medial forebrain bundle, markedly reduced the number of imipramine receptors on the caudal side of the lesion, while a significant accumulation was still evident on the rostral aspect. These results suggest that imipramine receptors are undergoing the process of orthograde axonal transport to terminals in the forebrain from the neuronal perikarya found in the nucleus raphe dorsalis. These receptors may also be undergoing retrograde transport back to their cell bodies of origin.

Animals↗
PubMed1998

Neurofilament subunits can undergo axonal transport without incorporation into Triton-insoluble structures.

We examined the form(s) in which NF subunits undergo axonal transport. Pulse-chase radiolabeling analyses with 35S-methioinine revealed that newly synthesized Triton-soluble NF subunits accumulated within axonal neurites elaborated by NB2a/d1 neuroblastoma prior to the accumulation of Triton-insoluble subunits. Gel chromatographic, immunological, ultrastructural, and autoradiographic analyses of Triton-soluble axonal fractions demonstrated that radiolabeled, Triton-soluble subunits were associated with NFs. Triton-soluble, radiolabeled axonal NF subunits were also detected within retinal ganglion cell axons following intravitreal injection of 35S-methioinine. Microinjected biotinylated subunits were prominent within axonal neurites of NB2a/d1 cells and cultured dorsal root ganglion neurons substantially before they were retained following Triton-extraction. Prevention of biotinylated subunit, but not dextran tracer, translocation into neurites by nocodazole confirmed that microinjected subunits did not enter axons merely due to diffusion or injection-based pressure. Immuno-EM confirmed the association of biotin label with axonal NFs. These findings point towards multiple populations of NF subunits within axons and leave open the possibility that axonal NFs may be more dynamic than previously considered.

Animals↗
PubMed1994

[32P]orthophosphate and [35S]methionine label separate pools of neurofilaments with markedly different axonal transport kinetics in mouse retinal ganglion cells in vivo.

Newly synthesized neurofilament proteins become highly phosphorylated within axons. Within 2 days after intravitreously injecting normal adult mice with [32P]orthophosphate, we observed that neurofilaments along the entire length of optic axons were radiolabeled by a soluble 32P-carrier that was axonally transported faster than neurofilaments. 32P-incorporation into neurofilament proteins synthesized at the time of injection was comparatively low and minimally influenced the labeling pattern along axons. 32P-incorporation into axonal neurofilaments was considerably higher in the middle region of the optic axons. This characteristic non-uniform distribution of radiolabel remained nearly unchanged for at least 22 days. During this interval, less than 10% of the total 32P-labeled neurofilaments redistributed from the optic nerve to the optic tract. By contrast, newly synthesized neurofilaments were selectively pulse-labeled in ganglion cell bodies by intravitreous injection of [35S]methionine and about 60% of this pool translocated by slow axoplasmic transport to the optic tract during the same time interval. These findings indicate that the steady-state or resident pool of neurofilaments in axons is not identical to the newly synthesized neurofilament pool, the major portion of which moves at the slowest rate of axoplasmic transport. Taken together with earlier studies, these results support the idea that, depending in part on their phosphorylation state, transported neurofilaments can interact for short or very long periods with a stationary but dynamic neurofilament lattice in axons.

Animals↗
PubMed1989

Low molecular weight GTP-binding proteins are associated with neuronal organelles involved in rapid axonal transport and exocytosis.

Recent evidence suggests that low molecular weight GTP-binding proteins may play important roles in a variety of membrane transport processes. In order to address the question of whether these proteins are involved in transport processes in the nerve axon, we have assessed their presence in rapid transport membranes from rabbit optic nerve. We report the characterization of a group of low molecular weight GTP-binding proteins which are constituents of rapid transport vesicles. Although these proteins are components of rapid transport vesicles, they are apparently not major rapidly transported species. They are localized in cytosolic as well as in membrane fractions of axons, and the membrane-associated form behaves as an integral membrane protein(s). These proteins are also found in association with a variety of vesicular and organellar components of neurons including coated vesicles, synaptic vesicles, synaptic plasma membranes, and mitochondria. We discuss the possible roles of these proteins in rapid axonal transport and exocytosis.

Animals↗
PubMed1990

Lysosomal activity at nodes of Ranvier during retrograde axonal transport of horseradish peroxidase in alpha-motor neurons of the cat.

Lysosomal activity at nodes of Ranvier of feline hindlimb alpha-motor neurons was examined by light and electron microscopical acid phosphatase (AcPase) histochemistry during retrograde axonal transport of intramuscularly injected horseradish peroxidase (HRP). Several nodes along the PNS parts of the alpha-motor axons of the HRP-injected side showed accumulations of AcPase-positive bodies in the constricted nodal axon segment and the adjacent paranodal axoplasm. Such lysosomal accumulations were most prominent in the ventral root and differed in number and intensity depending on survival time after the HRP injection. At nodes showing high AcPase activity the axoplasm proximal to the nodal midlevel was occupied by many small, AcPase-positive, vesiculotubular profiles. Larger AcPase-positive bodies were mainly situated distal to the nodal midlevel. Double incubation for demonstration of both HRP and AcPase activity showed similar accumulations of AcPase-positive bodies at some of the HRP-transporting nodes. The AcPase activity differed considerably between nodes exhibiting comparable levels of HRP-positivity. Many of the AcPase-positive bodies also contained HRP reaction product. At some HRP-positive nodes the number of AcPase-positive bodies situated in the paranodal axon-Schwann cell network was elevated when compared to nodes of the contralateral, control side. In contrast to the PNS nodes, the nodal occurrence and distribution of lysosomes in the CNS part of alpha-motor axons seemed not to be affected by HRP transport. These observations support our previous proposal that nodes of Ranvier in the PNS parts of alpha-motor axons, in contrast to their CNS nodes, possess an ability to control passage of and initiate lysosomal degradation of axonally transported substances. Such an ability may provide a protective function to the motor neuron by restricting the intraneuronal transport of materials imbibed by the axon terminals outside the CNS.

Acid Phosphatase↗
PubMed1981

Pressure-induced optic nerve axonal transport interruption in cat eyes.

After intravitreal injection of tritiated leucine, optic nerve axonal transport was studied in 30 cat eyes by tissue radioautography. Twenty-five experimental eyes were examined after four hours of acute pressure elevation with perfusion pressures maintained at 20 to 70 mm Hg. In five control specimens, intraocular pressures were maintained at 10 mm Hg for the four-hour interval. The extent of leucine accumulation, as seen by radioautographs, was inversely proportional to the perfusion pressure. Accumulation was limited to the region fo the lamina cribrosa. The anatomic distribution and pressure response of this transport interruption were similar to those seen in primate eyes studied under similar conditions.

Animals↗
PubMed1979

Double labelling of blanched neurons in the central nervous system of the rat by retrograde axonal transport of horseradish peroxidase and iron dextran complex.

The retrograde axonal transport of an iron-dextran complex leads to a labelling of neural cell bodies in the central nervous system (CNS) of the rat. This tracer and horseradish peroxidase (HRP) can both be demonstrated histochemically in same cell bodies of intralaminar thalamic neurons in the central lateral nucleus, after injection of iron-dextran in the striatum and injection of HRP in the motor cortex. This is made possible by processing the sections first for HRP and then for ferric ions by Perl's reaction. This method allows an accurate demonstration of divergent axonal projections and is compatible with cytoarchitectonic studies on the same sections.

Animals↗
PubMed1980

Preparation and retrograde axonal transport of an antiviral drug/horseradish peroxidase conjugate.

Recurrent Herpes simplex virus infections of the cornea are currently treated with antiviral drugs administered locally during periods of active infection. We have examined the feasibility of an alternate approach to treating recurrent infection, that of delivering an antiviral drug by axonal transport to cell somata in the trigeminal ganglion where the latent virus is thought to reside. We have coupled an antiviral drug to horseradish peroxidase (HRP), a protein which is readily transported retrogradely in corneal sensory axons to ganglion cell somata in the trigeminal ganglion. The antiviral drug 5-iodo-5'-amino-2',5'-dideoxyuridine (AIDU) was synthesized with 125I and coupled to horseradish peroxidase by Schiff base formation between the 5' amino group and aldehydes generated on the carbohydrate of the HRP following short periodate oxidation. The useful ratio of AIDU:HRP was 2-9; higher ratios resulted in an insoluble product. Sodium dodecylsulfate (SDS) acrylamide gel electrophoresis of the drug-protein conjugate revealed considerable aggregation and the isoelectric point of HRP was changed from 8.1 to 4.4-5.8 following the coupling procedure. Despite evidence that the protein conformation was considerably altered, the specific enzymatic activity of the final product was 58% of native HRP and the drug-protein conjugate was still strongly transported retrogradely. Retrograde transport of this conjugate was demonstrated by autoraiography of the trigeminal ganglion neurons 24 h after corneal injection of the [125I]AIDU/HRP.

Animals↗
PubMedDate not supplied

In vitro low frequency electromagnetic field effect on fast axonal transport.

The objective of this study was to evaluate the effects of a low frequency electromagnetic field on fast axonal transport for future neuroprosthetic applications. Changes in speeds and densities of retrograde fast organelle transport in rat sciatic nerve preparations were measured in vitro upon exposure to 15 and 50 Hz pulsed magnetic fields with peak intensities of 4.4 and 8.8 mT. Maximum current density of the induced eddy current was calculated to be about 40 microA/cm2. Video enhanced differential interference contrast microscopy was used to record axons supporting active organelle transport. Strong effects were observed in myelinated axons (cessation of transport in up to 10 min). Such effects may eventually be used as part of a neuroprosthesis to noninvasively modify or couple to various parts of the nervous system.

Animals↗
PubMed1980

Fast axonal transport in auditory neurons of the guinea pig: a rapidly turned-over glycoprotein.

Proteins of the fast component of axonal transport were analyzed by one- and two-dimensional polyacrylamide gel electrophoresis in the guinea pig spiral ganglion, which has its cell bodies in the cochlea and its axons in the eighth cranial nerve projecting to the ipsilateral cochlear nucleus. We found that we could easily identify the proteins of the fast component even though these axons are only about 3 mm long because the cochlea minimized diffusion of labeled precursor into the cochlear nucleus. The composition of the fast component of the spiral ganglion cells was similar, but not identical, to the fast component of guinea pig retinal ganglion cells. One difference was the predominance in the spiral ganglion cell fast component of a rapidly turned-over glycoprotein (RTGP) with a molecular weight of 110,000-140,000 and an isoelectric point of 5.0 RTGP accumulated in the cochlear nucleus for just the first 3 hr after the application of the labeled precursor and then rapidly disappeared, whereas the other major fast component polypeptides continued to accumulate for 12-24 hr. RTGP was also tentatively identified in the fast component of retinal ganglion cells, but was not as prominently labeled relative to the other fast-component proteins in those cells. The rapid disappearance of RTGP from spiral ganglion cell terminals in the cochlear nucleus may be a result of secretion, perhaps as part of a synaptic vesicle, or retrograde transport as a feedback signal. The difference in the relative amounts of RTGP found in spiral ganglion and retinal ganglion cell terminals may reflect differences in the fundamental properties of the two groups of neurons.

Animals↗
PubMed1986

Axonal transport of rabies virus in the central nervous system of the rat.

Stereotaxic inoculation of rabies virus into specific nuclei in the central nervous system has been used for the investigation of the central neural transport mechanisms of viral information. The infection was monitored by specific fluorescence and peroxidase studies and the titration of viral infectivity in dissected brain areas. Twenty-four hours after inoculation into the striatum, cortex, or substantia nigra, infected neurons were detected only in cells from areas and nuclei which were related to the site of inoculation. The distribution of infected neurons showed that retrograde axoplasmic flow plays a determining role in the transport of rabies virus 24 hours after delivery of virus to specific target nuclei. Local destruction of neurons by kainic acid at the site of viral inoculation did not prevent the uptake and subsequent retrograde axonal transport of virus. There was an overall correlation between the major neural connections of the inoculated areas (e.g. the striatum) and the infected areas 24 hours later (e.g. the substantia nigra).

Animals↗
PubMed1991

Identification of Ser-55 as a major protein kinase A phosphorylation site on the 70-kDa subunit of neurofilaments. Early turnover during axonal transport.

The 70-kDa neurofilament protein subunit (NF-L) is phosphorylated in vivo on at least three sites (L1 to L3) (Sihag, R. K. and Nixon, R. A. (1989) J. Biol. Chem. 264, 457-464). The turnover of phosphate groups on NF-L during axonal transport was determined after the neurofilaments in retinal ganglion cells were phosphorylated in vivo by injecting mice intravitreally with [32P]orthophosphate. Two-dimensional phosphopeptide maps of NF-L from optic axons of mice 10 to 90 h after injection showed that radiolabel decreased faster from peptides L2 and L3 than from L1 as neurofilaments were transported. To identify phosphorylation sites on peptide L2, axonal cytoskeletons were phosphorylated by protein kinase A in the presence of heparin. After the isolated NF-L subunits were digested with alpha-chymotrypsin, 32P-peptides were separated by high performance liquid chromatography on a reverse-phase C8 column. Two-dimensional peptide mapping showed that the alpha-chymotrypsin 32P-peptide accepting most of the phosphates from protein kinase A migrated identically with the in vivo-labeled phosphopeptide L2. The sequence of this peptide (S-V-R-R-S-Y) analyzed by automated Edman degradation corresponded to amino acid residues 51-56 of the NF-L sequence. A synthetic 13-mer (S-L-S-V-R-R-S-Y-S-S-S-S-G) corresponding to amino acid residues 49-61 of NF-L was also phosphorylated by protein kinase A. alpha-Chymotryptic digestion of the 13-mer generated a peptide which contained most of the phosphates and co-migrated with the phosphopeptide L2 on two-dimensional phosphopeptide maps. Edman degradation of the phosphorylated 13-mer identified serine residue 55 which is located within a consensus phosphorylation sequence for protein kinase A as the major site of phosphorylation. Since protein kinase A-mediated phosphorylation influences intermediate filament assembly/disassembly in vitro, we propose that the phosphopeptide L2 region is a neurofilament-assembly domain and that the cycle of phosphorylation and dephosphorylation of Ser-55 on NF-L, which occurs relatively early after subunit synthesis in vivo, regulaaes a step in neurofilament assembly or initial interactions during axonal transport.

Amino Acid Sequence↗
PubMed1986

A radiolabelled pulse for the simultaneous study of anterograde and retrograde axonal transport.

A technique is described for producing a pulse of [35S]methionine-labelled material which is axonally transported in amphibian sciatic nerve maintained in vitro. Using a position-sensitive detector of ionizing radiation, it is possible to continuously observe the movement of the pulse in the anterograde direction and, following turnaround at a ligature, the movement of a fraction of the pulse in the retrograde direction. Two sources of contaminant activity, which would otherwise interfere with observation of the pulse, are discussed and shown to be avoidable.

Animals↗
PubMed2000

Cilostazol prevents impairment of slow axonal transport in streptozotocin-diabetic rats.

We studied the effects of cilostazol, an antiplatelet and vasodilating agent, on axonal transport patterns of cytoskeletal proteins in the motor fibers of sciatic nerve of streptozotocin-induced diabetic rats. Proteins labeled with L-[35S]methionine in 6-mm consecutive segments of the nerve were analyzed electrophoretically following fractionation into Triton-soluble and-insoluble subpopulations. Transport rates of proteins (particularly neurofilaments) in slow component a were reduced by 50% 2 weeks after labeling (4 weeks after streptozotocin). An apparent reduction of tubulin and actin was observed at later intervals after induction of diabetes. Actin transported in slow component b was also impaired, though to a lesser extent than in component a. Cilostazol prevented transport impairment of both slow components a and b without affecting hyperglycemia or reduction in body weight gain. These results suggest that in sciatic motor fibers early defects in slowly transported proteins are more marked in slow component a, and that impairment may be caused primarily by hemodynamic abnormalities.

Animals↗
PubMed1980

Axonal transport of the molecular forms of acetylcholinesterase in chick sciatic nerve.

Acetylcholinesterase (AChE) polymorphism was studied in the sciatic nerve of 4-week-old Leghorn chicks, by sucrose gradient sedimentation analysis. Four main AChE molecular forms were found with sedimentation coefficients of 5S, 7.5S, 11.5S and 20S respectively. Axonal transport of each of these forms was investigated on the basis of the enzyme accumulation kinetics measured on both sides of nerve transections and of the enzyme redistribution kinetics in nerve segments isolated in vivo. After nerve transection, 11.5S and 20S forms accumulated faster in the anterograde than in the retrograde direction and also much faster than 5S and 7.5S forms in the anterograde direction. Retrograde accumulations of 5S and 7.5S were faint or negligible. In addition, 1 h after nerve cutting, the accumulation rates for 11.5S and 20S forms (but not for 5S and 7.5S) fell, in both directions, to about one-third of their initial values, probably owing to reversal of axonal transport at the axotomy site. Local protein synthesis inhibition by cycloheximide did not affect the accumulation of 11.5S and 20S in front of a transection, at least during the first hours, but reduced that of 5S and 7.5S by about 40%. In isolated nerve segments in vivo, the rapidly mobile fraction of AChE was estimated to constitute 23% of the total enzyme activity present in the nerve, 14% of it moving in an anterograde and 9% in a retrograde direction. A small amount of 11.5S molecules (approx. 20%) was in rapid transit (two-thirds in the anterograde and one-third in the retrograde direction), whereas almost all the 20S--about 90%--migrated rapidly (two-thirds forwards and one-third backwards). Anterograde velocities of 408 +/- 94 and 411 +/- 161 mm/day respectively were estimated for the 11.5S and 20S forms. Their respective retrograde velocities were 175 +/- 85 and 145 +/- 107 mm/day. Assuming that the totality of 5S and 7.5S molecules are moving in the anterograde direction, their accumulation rates were consistent with the average anterograde velocities of 2.9 +/- 1.3 and 5.1 +/- 1.4 mm/day, respectively.

Acetylcholinesterase↗