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 361 records · Page 20Linked to original sources
PubMed1982

Transfer of axonally transported phospholipids into myelin isolated from the rabbit optic pathway.

The contribution of the axonal transport to the biosynthesis of myelin phospholipids was investigated in the rabbit optic pathway. A double labeling technique was used. The same animals were injected with one isotope intravitreally and the other intraventricularly. This procedure allows double labeling of the optic nerves, optic tracts, lateral geniculate bodies (LGB), and superior colliculus (SC). The precursors simultaneously injected were: [1-14C]palmitate (15 microCi intravitreally in both eyes or 50 microCi intraventricularly) and [2-3H]glycerol (50 microCi intravitreally in both eyes of 100 microCi intraventricularly). Twenty four hours and 10 days after the injections, myelin was purified from pooled optic nerves and optic tracts as well as from pooled LGBs or SCs. The phospholipids were extracted and then separated by thin-layer chromatography; the specific radioactivity of the various classes of phospholipids was determined. Using both administration routes of C- or 3H-precursors, the distribution of label and specific radioactivity of myelin phospholipids in the retina and in all other optic structures were very similar. Phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine + phosphoinositol were preferentially labeled with both precursors. These results suggest that, in the rabbit optic pathway the phospholipids synthesized in the retinal ganglion cells and transported along the axons, could undergo transaxonal transfer into myelin.

Animals↗
PubMed1982

Rapid migration of inositol phospholipids with axonally transported substances in the rabbit optic pathway.

Following an intraocular injection of myo-[2-3H]inositol, the axonal transport of labelled water-soluble substances and inositol phospholipids was investigated. Evidence was obtained for a rapid axonal transport of a relatively small amount of labelled inositol phospholipids. In contrast to other axonally transported phospholipids, there was no significant accumulation of labelled, rapidly transported inositol phospholipids in the nerve terminal region at later time intervals following the isotope administration.

Animals↗
PubMed1979

Superior sensitivity of conjugates of horseradish peroxidase with wheat germ agglutinin for studies of retrograde axonal transport.

We have compared the retrograde axonal transport of horseradish peroxidase (HRP), to the retrograde transport of HRP conjugated with wheat germ agglutinin (WGA). Morphometric studies have shown that WGA-HRP conjugates were 40 times more sensitive than free HRP, in the tracing of retrograde connections from the rat submandibular gland to the superior cervical ganglion. Also, WGA-HRP was more sensitive than free HRP in the tracing of retrograde connections from the rat tongue to the hypoglossal nucleus. Our findings with WGA-HRP are consistent with the observations by Schwab et al. who reported (-125I) WGA is a highly sensitive retrograde tracer (Brain Research 152:145, 1978 (22)).

Animals↗
PubMed1988

Pressure-induced inhibition of fast axonal transport of proteins in the rabbit vagus nerve in galactose neuropathy: prevention by an aldose reductase inhibitor.

Fast and slow anterograde axonal transport and retrograde axonal transport of proteins were studied in the mainly non-myelinated sensory fibres of the vagus nerve of rabbits fed a diet of 50% galactose over a period of 29 days. Galactose feeding had no effect on the rate or protein composition of slow transport nor on the amount of retrogradely transported proteins. There was a slight retardation of fast transported proteins although their composition was unchanged. The galactose feeding led to a significant increase (p less than 0.005) in nerve water content and nerve galactitol but no significant change in myo-inositol. When 20 mm Hg pressure was applied locally to the cervical vagus nerve, fast transported proteins accumulated proximal to the compression zone in the galactose-fed but not in control rabbits. Administration of the aldose reductase inhibitor Statil (ICI 128436) throughout the experiment prevented the increased susceptibility to pressure and the increase in nerve galactitol and water content. The effects of pressure are similar to those found in the streptozotocin-diabetic rat although the underlying mechanisms may differ.

Aldehyde Reductase↗
PubMed2003

Axonal transport of eukaryotic translation elongation factor 1alpha mRNA couples transcription in the nucleus to long-term facilitation at the synapse.

Long-term synaptic plasticity requires both gene expression in the nucleus and local protein synthesis at synapses. The effector proteins that link molecular events in the cell body with local maintenance of synaptic strength are not known. We now show that treatment with serotonin (5-HT) that produces long-term facilitation induces the Aplysia eukaryotic translation elongation factor 1alpha (Ap-eEF1A) as a late gene that might serve this coupling function in sensory neurons. Although the translation factor is induced, it is not transported into axon processes when the stimulation with 5-HT was restricted to the cell body. In contrast, its mRNA is transported when 5-HT was applied to both cell body and synapses. Intracellular injection of antisense oligonucleotides or antibodies that block the induction and expression of Ap-eEF1A do not affect the initial expression of long-term facilitation but do block its maintenance beyond 24 h. The transport of eEF1A protein and its mRNA to nerve terminals suggests that the translation factor plays a role in the local protein synthesis that is essential for maintaining newly formed synapses.

Animals↗
PubMed2003

Impaired fast axonal transport in neurons of the sciatic nerves from dystonia musculorum mice.

Dystonia musculorum (dt) mice suffer from a severe sensory neuropathy caused by mutations in the gene encoding the cytoskeletal cross-linker protein dystonin/bullous pemphigoid antigen 1 (Bpag1). Loss of function of dystonin/Bpag1 within neurons leads to a loss in the maintenance of cytoskeletal organization and to the development of focal axonal swellings prior to death of the neuron. In the present study, we demonstrate that neurons within the sciatic nerves of dt27J mice undergo axonal degeneration as has been previously reported for the dorsal roots. Furthermore, ultrastructural studies reveal a perturbed organization of the neurofilament and microtubule networks within the axons of sciatic nerves in dt27J mice. The disrupted cytoskeletal organization suggested that axonal transport is affected in dt mice. To address this, we assessed fast axonal transport by measuring the rate of accumulation of acetylcholinesterase (AChE) proximal and distal to a surgically introduced ligature on the sciatic nerves of normal and dt27J mice. Our findings demonstrate that axonal transport of AChE in both orthograde and retrograde directions is markedly affected, and allow us to conclude that axonal transport defects do exist in the sciatic nerves of dt27J mice.

Acetylcholinesterase↗
PubMed1989

Axonal transport of neuronal antigens characteristic of subpopulations of central nervous system (CNS) neurons.

Monoclonal antibodies (MAbs) are useful for the identification of nervous system antigens localized to neuronal subpopulations. We have examined the transport of the corresponding antigens of four such MAbs in guinea pig retinal ganglion-cell axons. Determination of the axonal transport rate of radiolabeled antigens allowed their assignment to one of the three major anterograde axonal transport rate components, each of which is through to convey a subcellular structural system in the axon. Antigens identified by three of the MAbs were found to be transported in slow component b of axonal transport, the component thought to convey the cytoplasmic matrix, and an antigen identified by the fourth MAb was found in slow component a, similarly thought to contain the linear cytoskeletal elements. Assignment of these antigens to the different rate components suggests that they may be associated with a particular structural system in neurons. Additionally, in cases where more than one nervous system cell type may express a particular antigen, the identity of the neuronal form of the antigen has been confirmed by its axonal transport. The roles that these antigens may play in the nervous system during normal axonal function and during neuropathogenesis can now be further examined.

Animals↗
PubMed2000

Effects of substance P and calcitonin gene-related peptide on axonal transport in isolated and cultured adult mouse dorsal root ganglion neurons.

Substance P and calcitonin gene-related peptide (CGRP) released from primary sensory neurons are known to play important roles in nociception and nociceptive transmission. In the present study, we attempted to clarify the roles of these neuropeptides in the regulation of axonal transport in sensory neurons. Cells were isolated from adult mouse dorsal root ganglia and cultured in F-12 medium containing fetal bovine serum for 48 h until their neurites were grown. These isolated and cultured DRG cells were mostly (>98%) small (diameter <25 microm) and medium (diameter, 25-40 microm) in size, and were immunoreactive for substance P and CGRP (85.9 and 66. 0% of total cells, respectively). Video-enhanced microscopy was applied to observe particles transported within neurites. Application of substance P (100 nM) decreased the number of particles transported in both anterograde and retrograde directions in each of DRG neurons tested (n=5). The instantaneous velocities of individual particles transported in anterograde and retrograde directions were also reduced by substance P. In contrast, alpha-CGRP (100 nM) increased the number of particles transported in both directions in each of DRG neurons tested (n=5), and also increased the instantaneous velocities of particles transported bidirectionally. Application of beta-CGRP (100-1000 nM) did not elicit any effect on axonal transport. Therefore, axonal transport in sensory neurons seems to be modulated by substance P and alpha-CGRP, both of which can be derived from its own and adjacent sensory neurons.

Animals↗
PubMed1995

The activation of protein kinase A pathway selectively inhibits anterograde axonal transport of vesicles but not mitochondria transport or retrograde transport in vivo.

To shed light on how axonal transport is regulated, we examined the possible roles of protein kinase A (PKA) in vivo suggested by our previous work (Sato-Yoshitake et al., 1992). Pharmacological probes or the purified catalytic subunit of PKA were applied to the permeabilized-reactivated model of crayfish walking leg giant axon, and the effect was monitored by the quantitative video-enhanced light microscopy and the quantitative electron microscopy. Dibutyryl cyclic AMP caused concentration-dependent transient reduction in the number of anterogradely transported small vesicles, while the retrogradely transported organelles and anterogradely transported mitochondria showed no decrease. This transient selective inhibition of anterograde vesicle transport was reversed by the application of a specific inhibitor of PKA (KT5720) in a concentration-dependent manner, and was reproduced by the application of the purified catalytic subunit of PKA and augmented by the application of adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S). Corresponding biochemical study showed that several axoplasmic proteins including kinesin were specifically phosphorylated by the activation of the PKA pathway. These findings suggest the possible roles of PKA in the regulation of the direction of the axonal transport in vivo. The finding that only vesicle transport but not mitochondria transport was inhibited also suggests that the transport of vesicles and that of mitochondria are differently regulated and might be supported by different motors.

Adenosine Triphosphate↗
PubMed1986

Impaired slow axonal transport in wobbler mouse motor neuron disease.

We studied slow axonal transport and morphometry of forelimb axons in wobbler mice and controls. In wobbler mice, the total radioactivity migrating with the slow transport was decreased by 50%. The velocity of transport also appeared to be reduced; 15 days following administration of a radioisotope, polypeptides migrating with slow component a of transport did not form a peak and remained mostly 2 mm from the spinal cord, while in controls slow component a was distributed as a peak which was located 4 mm from the cord. The ratios of the 68-kDa neurofilament subunit to tubulin and actin were significantly decreased (p less than 0.01 and p less than 0.005, respectively). This finding is consistent with a preferential reduction of the radioactivity migrating with neurofilament proteins in wobbler mice. Moreover, both the size and number of myelinated axons were markedly diminished, but their length was not significantly different, indicating that dying-back does not take place in axons of wobbler mice up to 12 mm from the spinal cord. The reduction in axonal transport may be due to the reduction in number and caliber of the axons and/or to reduced protein synthesis in cervical lower motor neurons; however, the abnormal distribution of the radioactive substance definitely results from impairment of the slow transport in the axons of the forelimb roots of wobbler mice. The transport impairment is not related to the presence of morphological changes in the perikaryon of wobbler mouse lower motor neurons, as it is much more widespread than would be expected if only altered neurons were involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1987

The axonal transport of dipeptidyl aminopeptidase II, angiotensin-converting enzyme and other peptidases in rat sciatic nerves.

The axonal transport of four peptidases with different subcellular localizations were examined in rat sciatic nerves by the double ligation technique. At 2 days after ligation, rapid retrograde axonal transport of the activity of dipeptidyl aminopeptidase II (a lysosomal enzyme), angiotensin-converting enzyme and leucyl aminopeptidase (membrane-bound enzymes), was found in the segment distal to the proximal ligation. On the other hand, prolyl endopeptidase (a cytosolic enzyme) showed neither anterograde nor retrograde rapid axonal transport. These results indicate that lysosomal and membrane-bound peptidases are transported retrogradely in rat sciatic nerves.

Animals↗
PubMed1980

Investigation of the axonal transport of three acidic, soluble proteins (14-3-2, 14-3-3, and S-100) in the rabbit visual system.

The question of whether three acidic, water-soluble proteins (14-3-2, 14-3-3, and S-100, the first and last known to be brain-specific) are axonally transported was investigated in the rabbit visual system. The water-soluble proteins were obtained from individual optic nerves, combined optic tracts and lateral geniculate bodies, superior colliculi, and, in some instances, retinas at various times (1--56 days) after monocular injections of [3H]leucine. These proteins were separated by a two-step polyacrylamide gel electrophoresis procedure that isolated 14-3-2, 14-3-3, and S-100 almost uncontaminated by other radioactivity. The isolated 14-3-2 and S-100 were demonstrated to be approx. 90% pure by a new method based on retarding the migration of these proteins by immunoadsorption during the first step of electrophoresis. An analysis of the radioactive labeling of the total soluble proteins (TSP) and the isolated acidic proteins revealed that: (1) S-100 was not axonally transported; (2) both 14-3-2 and 14-3-3 were part of one of the slow components of axonal transport (2--4 mm/day); (3) the radioactivity of 14-3-2 and 14-3-3 represented about 2.7% and 3.2%, respectively, of the radioactivity incorporated into the axonally transported TSP; (4) the ultimate distributions of the radioactively labeled 14-3-2 and 14-3-3 were the same (about 70% of each destined for the superior colliculus) and differed from that of the TSP; and (5) the rates of catabolism of the axonally transported 14-3-2 and 14-3-3 were slightly greater than that of the TSP, with half-lives for 14-3-2 and 14-3-3 estimated to be 11 and 10 days, respectively.

Animals↗
PubMed1989

Slow axonal transport impairment of cytoskeletal proteins in streptozocin-induced diabetic neuropathy.

The impairment of slow axonal transport of cytoskeletal proteins was studied in the sciatic nerves of streptozocin-diabetic rats. [35S]Methionine was unilaterally injected into the fourth lumbar ganglion and spinal cord, to label the sensory and motor axons, respectively, and then the polymerized elements of the cytoskeleton and the corresponding soluble proteins were analyzed separately. In addition, the pellet/supernatant ratio for tubulin and actin was also assessed. Our results indicate that the velocity of slow component a (SCa) of axonal transport, particularly that of neurofilaments, was strongly reduced (by 60%) in sensory axons. At the same time, a decreased pellet/supernatant ratio of tubulin, possibly owing to a depolymerization of stable microtubules, was also observed. The transport of slow component b (SCb) of axonal transport was also impaired, but the extent of this impairment could not be precisely evaluated. In contrast, motor axons showed little or no impairment of both SCa and SCb at the time studied, a result suggesting a delayed development of the neuropathy in motor axons.

Animals↗
PubMed1991

Hypothyroidism reduces the rate of slow component A (SCa) axonal transport and the amount of transported tubulin in the hyt/hyt mouse optic nerve.

Thyroid hormone deficiency in the developing brain leads to disorders of neuronal process growth. This is evidenced by reduced axonal and dendritic size and complexity (Garza et al.: Developmental Brain Research 43:287-297, 1988; Ruiz-Marcos: Iodine and the Brain. New York: Plenum Press, pp 91-102, 1989). These findings may be related to alterations in the neuronal cytoskeleton in hypothyroidism, such as reduced or abnormal microtubular number and density (Faivre et al.: Developmental Brain Research 8: 21-30, 1983), and altered assembly, stabilization, and composition of microtubule protein in the hypothyroid brain. Neurofilaments also contribute to axonal caliber and process stability. Similar to microtubules, certain properties of neurofilaments are altered in developing hypothyroid axons (Marc and Rabie: International Journal of Developmental Neuroscience 3: 353-358, 1985; Faivre et al.: Developmental Brain Research 8:21-30, 1983) that may affect axonal caliber and process stability. Normal process growth is predicted on formation of appropriate numbers of microtubules and on the normal synthesis and axonal transport of cytoskeletal components [tubulin, microtubule associated proteins (MAPs), and neurofilament proteins]. Hypothyroidism might alter the neuronal cytoskeleton and neuronal growth either by affecting the developmental programs for expression of specific isoforms of cytoskeletal proteins or by changing the delivery of cytoskeletal proteins via slow axonal transport, particularly slow component a (SCa). Previous studies had demonstrated changes in the amount of specific microtubule protein isoforms and mRNAs (Stein et al.: Iodine and the Brain. New York: Plenum Press, pp 59-78, 1989a). To further elucidate the molecular basis for process growth abnormalities in the hypothyroid brain, we investigated slow axonal transport in the mouse to determine the effects of thyroid hormone deficiency on the rate and composition of SCa. Comparisons of SCa in the optic nerve of hyt/hyt hypothyroid mouse and euthyroid hyt/+ littermates and euthyroid progenitor strain, BALB/cBY +/+ mice, indicated that the velocity of SCa was significantly reduced in hyt/hyt optic nerve relative to hyt/+ and +/+. The axonal transport rate for tubulin, which is carried in SCa, was 0.118 mm/day in the hyt/hyt optic nerves. This rate was significantly different for the tubulin rates for the hyt/+ optic nerves (0.127 mm/day) and for the +/+ optic nerves (0.138 mm/day). Neurofilament proteins, as measured by the 140,000 daltons component, NFM, also appeared to be reduced in velocity in the hyt/hyt versus the hyt/+ and +/+ optic nerves.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗
PubMed1993

Axonal transport and the cytoskeleton.

Great advances in the field of axonal transport have been made in the past year, including the identification of new molecular motors associated with microtubules and actin. In addition, studies on the mechanisms of bidirectional fast axonal transport have clarified new aspects of this process, such as the isolation of a kinesin-binding protein, kinectin, and the finding that phosphorylation regulates kinesin's dissociation from membranous organelles. New approaches to studying slow transport of cytoskeletal proteins have provided further evidence that the axonal cytoskeleton in mammalian systems is largely stationary, although a dynamic exchange occurs between polymers and a small pool of moving subunits.

Animals↗
PubMed1995

Age-dependent uptake and retrograde axonal transport of exogenous albumin and transferrin in rat motor neurons.

This study presents evidence for retrograde axonal transport of exogenous albumin and transferrin in adult brainstem motor neurons, whereas plasma proteins are not transported in neonatal motor neurons. The plasma protein uptake in motor neurons was dose-dependent, suggesting a nonspecific (fluid-phase) uptake mechanism. Further evidence for nonspecific uptake of exogenous transferrin in the motor neuron was found in the presence of transferrin receptor only on the soma and not on the axon terminal. The immunoreaction product of the exogenous plasma proteins was localized as perinuclear granules in association with the lysosomal system, as verified by staining for the lysosomal marker cathepsin D and by ultrastructural examinations. The results suggest that albumin and transferrin derived from hepatic synthesis gain access to motor neurons nonspecifically by retrograde axonal transport, whereas transferrin derived from intracerebral synthesis specifically gains access to motor neurons due to receptor-mediated uptake at the soma of the neuron. The lack of plasma proteins in developing motor neurons suggests that retrograde axonal transport of plasma proteins has no significance for developing axons. Plasma proteins have a potential for transporting toxic metals to motor neurons. Intraneuronal uptake of aluminum-transferrin either by nonspecific uptake in axon terminals or by receptor-mediated uptake at the soma may have a role in the pathogenesis of the motor neuron disease amyotrophic lateral sclerosis.

Aging↗