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At least 145 records · Page 8Linked to original sources
PubMed1988

Standardized intravitreal injections: evaluation of the effect of anesthesia on rapid axonal transport in the optic nerve.

Retinal ganglion cells incorporate intravitreally injected [3H]leucine into proteins that are transported orthogradely in optic axons to the superior colliculus. Since optic projections in the albino rabbit are nearly totally crossed, an agent suspected to alter axonal transport can be applied to one optic nerve after bilateral intravitreal injection of [3H]leucine; any reduction in radioactivity transported to the contralateral superior colliculus can then be quantified. Such studies require symmetric uptake and incorporation of precursor into ganglion cell proteins. A technique is described for intravitreal injections that reproducibly produces symmetric uptake of [3H]leucine. Using this technique, we determined that retrobulbar injected lidocaine in clinically used doses (2-4%) does not affect rapid axonal transport, while colchicine (a known inhibitor of axonal transport) blocks transport in a dose-related fashion.

Anesthesia↗
PubMed1983

Axonal transport of the molecular forms of acetylcholinesterase in developing and regenerating peripheral nerve.

In chick sciatic nerve, acetylcholinesterase (AChE) occurs in four main molecular forms characterized by their sedimentation coefficients in sucrose gradients, referred to as G1 (5S), G2 (7.5S), G4 (11S), and A12 (20S). Under normal conditions, we previously showed by accumulation technique that the G4 and A12 forms are rapidly transported along the axons, whereas G1 and G2 are carried much more slowly. Here, we used to the same technique to study the anterograde axonal transport of these different AChE forms during normal axonal growth and experimental regeneration. During the first 2 months after hatching, G4 and A12 transport virtually doubled, whereas G1 + G2 transport increased only slightly. After nerve cutting, crushing, or freezing, the flow rates of G1 + G2 and G4 in the regenerating proximal stump decreased by 75% at 4 to 7 days compared with control values and that of A12, by 90 to 95%. In crushed and frozen nerves the transport of all four AChE forms slowly recovered thereafter, but failed to attain control values even after 7 weeks. In cut nerves, on the contrary, no significant recovery of G1 + G2, or G4 transport occurred, but A12 transport began to recover by day 7. Taken together, our results show that axonal transport of G1 + G2, G4, and A12 is selectively regulated in chick sciatic nerve, and suggest that the A12 form of AChE might have a special role and/or destination in regenerating axons.

Acetylcholinesterase↗
PubMed1982

A study of the motion of organelles which undergo retrograde and anterograde rapid axonal transport in Xenopus.

1. Axonally transported organelles were detected optically in myelinated axons from Xenopus laevis at room temperature (21-23 degrees C). Details of the motion of organelles which were transported in the retrograde and anterograde directions were studied using filmed records.2. A group of 133 organelles with a mean retrograde velocity of 0.91 mum/sec was compared with a group of thirty-nine organelles with a mean anterograde velocity of 0.93 mum/sec.3. Averaged power spectra of the positional deviations about the mean positional change through time were constructed for organelles which travelled in the retrograde and anterograde directions. Most of the power in the two spectra was at frequencies below 0.2 Hz and each contained a single peak at 0.02-0.04 Hz. The power spectrum for retrograde organelle motion had a magnitude about twice that for anterograde organelle motion.4. Estimates of the instantaneous velocity of organelles which travelled in either direction varied smoothly with time. Instantaneous velocity was not a smooth function of organelle position, (i.e. was ;saltatory').5. Histograms of the estimates for the groups of organelles whose major motion was retrograde or anterograde were broad, covering a range of about 3 mum/sec, were unimodal, and passed through zero to include a small group of values which indicated motion in the opposite (minor) direction.6. Organelles spent, on average, more time moving in the minor direction the lower their mean velocity.7. The variation in instantaneous velocity was greater for organelles which travelled in the retrograde direction than for those which travelled in the anterograde direction. No correlation was found between the variation of instantaneous velocity and the mean velocity of the organelles.8. Images of organelles occasionally appeared to rotate while the organelle continued to move in the major direction of travel.9. Evidence is presented that spatially related properties of the axon influence organelle velocity and that this influence is common to organelles which travel in the two major directions.10. A hypothesis is presented to account for the findings. This supposes that each organelle travels through a stationary axoplasm and is propelled by the resultant of two opposing driving forces whose relative magnitude fluctuates with time. Spatially dependent properties of the axoplasm modify the postulated time-related cycle of motion.

Animals↗
PubMed1981

Axonal transport in transplanted frog sciatic nerve.

Axonal transport was studied in transplanted frog sciatic nerves-dorsal ganglia for periods up to three months. The ganglia were either labeled prior to, or after varying periods of transplantation and the distribution of labeled proteins compared. The survival of the preparations was assessed by studying their ability to transmit compound action potentials, to maintain axonal transport and by their ultrastructural appearance. The sensory neurons retained their fast axonal transport and excitability during the transplantation periods. Morphologically about 30% of the axons appeared normal after one month of transplantation. The amount and distribution of protein incorporated radioactivity in the ganglia and the nerve changed with time but the decrease in the ganglia was not accompanied by a corresponding increase in the nerve. There was no evidence for a distinct slow phase of transport in spite of a functional fast transport system. The results indicate that either slow transport stops when the normal balance between release, degradation and recirculation is distributed by the presence of a ligature or that there is a continuous change in the composition of transported material with the time after labeling which is not reflected in altered transport characteristics.

Animals↗
PubMed1988

Rapid axonal transport as a chromatographic process: the use of immunocytochemistry of ligated nerves to investigate the biochemistry of anterogradely versus retrogradely transported organelles.

The distribution and axonal transport of cholinergic organelles has been studied in the rat motor system, using immunofluorescence methods and a cytofluorimetric technique for quantification of immunoreactive material. Crush-operated spinal roots and sympathectomized sciatic nerves were sectioned longitudinally and incubated with antisera against p38, SV2, CGRP, chromogranin A (Chr A), synapsin I (SYN I), and with RASVA (rabbit anti-synaptic vesicle antiserum). Motor endplates were also studied. It was observed that proximally accumulating organelles--i.e., organelles which were in transport distally in the axons--contained RASVA-like immunoreactivity (LI) p38, SV2, CGRP-LI, Chr A-LI, and SYN I-LI. Retrogradely transported organelles, however, contained only p38 and SV2 in addition to RASVA-LI, but virtually no CGRP-LI, ChrA-LI, or SYN I-LI. It is suggested that the rapid axonal transport mechanism operates in the nerves like a chromatographic process, which allows the concentration in the axons, proximal or distal to the crush, of organelles in anterograde or retrograde transport, respectively. The technique of nerve crushes in combination with immunocytochemistry can therefore be used to investigate the biochemical composition of organelles in transit along the axon, and give information on neurobiological events occurring in these long processes leading to the nerve endings. In this study, biochemical differences between anterogradely and retrogradely transported cholinergic organelles in the motor neuron of the rat have been observed, and were related to suggested events in the endplate.

Acetylcholinesterase↗
PubMed2001

Low-concentration lidocaine rapidly inhibits axonal transport in cultured mouse dorsal root ganglion neurons.

BACKGROUND: Axonal transport plays a critical role in supplying materials for a variety of neuronal functions such as morphogenetic plasticity, synaptic transmission, and cell survival. In the current study, the authors investigated the effects of the analgesic agent lidocaine on axonal transport in neurites of cultured mouse dorsal root ganglion neurons. In relation to their effects, the effects of lidocaine on the growth rate of the neurite were also examined. METHODS: Isolated mouse dorsal root ganglion cells were cultured for 48 h until full growth of neurites. Video-enhanced microscopy was used to observe particles transported within neurites and to measure the neurite growth during control conditions and in the presence of lidocaine. RESULTS: Application of 30 microM lidocaine immediately reduced the number of particles transported in anterograde and retrograde axonal directions. These effects were persistently observed during the application (26 min) and were reversed by lidocaine washout. The inhibitory effect was dose-dependent at concentrations from 0.1 to 1,000 microM (IC50 = 10 microM). In Ca2+-free extracellular medium, lidocaine failed to inhibit axonal transport. Calcium ionophore A23187 (0.1 microM) reduced axonal transport in both directions. The inhibitory effects of lidocaine and A23187 were abrogated by 10 microM KN-62, a Ca2+-calmodulin-dependent protein kinase II inhibitor. Application of such low-concentration lidocaine (30 microM) for 30 min reduced the growth rate of neurites, and this effect was also blocked by KN-62. CONCLUSIONS: Low-concentration lidocaine rapidly inhibits axonal transport and neurite growth via activation of calmodulin-dependent protein kinase II.

Anesthetics, Local↗
PubMed1987

Proteins of fast axonal transport in regenerating rat sciatic sensory axons: a conditioning lesion does not amplify the characteristic response to axotomy.

The regeneration rate of axons following injury can be influenced by the past history of the neuron: if an axon received a "conditioning" lesion its regeneration rate from a subsequent "test" lesion is increased. Because regeneration is associated with the increased synthesis and fast axonal transport of growth-associated proteins of unknown functions, we investigated whether the increased regeneration rate (to 81%) seen in conditioned rat sciatic sensory axons following a test lesion was associated with an amplification of the increase in growth-associated protein expression. The test lesion did not produce any amplification of the increase in growth-associated protein expression resulting from the preceding conditioning lesion. We conclude that this aspect of the cell body reaction to axotomy is not involved in the conditioning lesion effect on regeneration rate, and, as a corollary, it appears that fast-transported proteins whose expression alters after axotomy are not involved in the regulation of the regeneration rate.

Animals↗
PubMed1996

Radioligand binding and autoradiographic visualization of adenosine transport sites in human inferior vagal ganglia and their axonal transport along rat vagal afferent neurons.

The present study has employed membrane-binding studies and in vitro autoradiography to demonstrate the presence of adenosine transport sites in human inferior vagal ganglia using [3H]nitrobenzylthioinosine ([3H]NBMPR), a potent inhibitor of adenosine transport. In addition, [3H]NBMPR was used to determine whether adenosine transport sites are subject to axonal transport along the rat vagus nerve. Binding of [3H]NBMPR to human inferior vagal ganglia membranes was saturable and reversible. Saturation experiments revealed a single class of high affinity-binding sites with a Kd of 93.73 +/- 23.13 pM and Bmax of 413.50 +/- 50.40 fmol/mg protein. In displacement experiments, the adenosine transport inhibitor dipyridamole was the most potent displacer of [3H]NBMPR binding (Ki = 42.7 +/- 28.0 nM). Adenosine itself was able to fully displace [3H]NBMPR binding with a Ki of 115.0 +/- 34.0 microM. The A1/A2a adenosine receptor agonist 5'-(N-ethylcarboxamido)-adenosine (NECA) was able to fully displace [3H]NBMPR binding in only one experiment at a concentration of 100 microM, yielding an affinity 1000-fold higher than its affinity for adenosine receptors. All competition curves obtained from displacement experiments displayed monophasic profiles, indicating the presence of a single class of [3H]NBMPR binding sites. Incubation of human inferior vagal ganglia sections with [3H]NBMPR (0.7 nM) revealed dense binding which appeared to be consistent with the distribution of neuronal cell bodies in this tissue. Following unilateral ligation of the vagus nerve in the rat, accumulation of [3H]NBMPR binding sites occurred both proximal and distal to the vagal ligatures. These results suggest that [3H]NBMPR binds with high affinity to a single class of adenosine transport sites, and that these sites are present on vagal afferent neurons in the human and undergo bidirectional axonal transport along the rat vagus nerve.

Adenosine↗
PubMed1980

Fast axonal transport in early experimental disc edema.

Previous work has documented impairment of slow axonal transport in papilledema, but the abnormalities in rapid transport were less certain. Therefore fast axonal transport was studied in 19 primate eyes subjected to ocular hypotony for 6 to 72 hr following surgical fistulization of the anterior chamber. Mild, irregular alterations in fast axonal transport were detected only after nerve head swelling was apparent. These changes in fast transport mechanisms in cases of nerve head edema occur after, and may be secondary to, impaired slow axoplasmic flow and the resultant axonal swelling. Furthermore, since prolonged complete interruption of axonal transport is theoretically inconsistent with the continued normal neuron function characteristic of papilledema and, moreover, since previous data shows a "slowdown" rather than complete blockade of axonal transport in papilledema, it is likely that in eyes with papilledema there does not exist a complete flock of axonal transport. Therefore we hypothesize that the swelling results when slow axoplasmic flow is locally slowed down but not totally stopped, with the axon distention producing secondary mild, irregular changes in fast axonal transport.

Animals↗
PubMed1984

Neuron-specific enolase: investigation on its possible retrograde axonal transport.

The possible rapid retrograde axonal transport of neuron-specific enolase was investigated employing a sensitive radioimmunoassay. The right sciatic nerve of rats was ligated and 6 and 24 h later the nerve was cut in two 5.0 mm segments immediately proximal and distal to the ligature. Similar segments were taken from the contralateral nerve as a control. No increase in the amount of neuron-specific enolase in the right-distal segment was observed indicating that the protein is not a component of retrograde axonal transport.

Animals↗
PubMed1988

Fast axonal transport alterations in amyotrophic lateral sclerosis (ALS) and in parathyroid hormone (PTH)-treated axons.

Video-enhanced contrast techniques have been used to study fast axonal transport of organelles in diseased and normal human axons. A broad perspective on the importance of axonal transport in the pathogenesis of human neurological disorders is presented and problems in dealing with human nerve summarized. Results from analysis of organelle traffic in axons from motor nerve in patients with amyotrophic lateral sclerosis (ALS) show: 1) higher mean speed of anterograde organelles, 2) lower mean speed of retrograde organelles, and 3) lower retrograde organelle traffic density. Hyperparathyroidism, another human clinical syndrome, can mimic ALS. The effect of parathyroid hormone (PTH) on axons in vitro is to increase the mean speed of both anterograde and retrograde organelle traffic. The dose response curve and time course of the PTH effect are delineated. Dihydropyridine calcium channel antagonists block the PTH effect, implicating extracellular calcium in the alteration of organelle traffic speed. The results are discussed in relation to neuronal function and the regulation of fast axonal transport.

Amyotrophic Lateral Sclerosis↗
PubMed1986

A proposal for a classification of neuropathies according to their axonal transport abnormalities.

Recent studies on axonal transport in experimental neuropathy are reviewed and the following combinations of pathological changes and underlying axonal transport abnormalities are proposed for a classification of polyneuropathies. Alterations of the anterograde transport of slow component a(SCa) leads to changes of the dimensions of the axon calibre without the occurrence either of overt neuropathy or fibre loss. Thus damming of SCa in beta,beta'-iminodiproprionitrile (IDPN) intoxication results in axonal swelling in nerve roots whereas decrease of SCa leads to atrophy distal to the swellings in IDPN intoxication and in streptozotocin induced diabetes as well. Decrease in the amount of material conveyed within the anterograde fast component (aFC) leads to acute axonal degeneration including break down of axons and fibre loss. This state occurs in acute hypoglycaemia and in doxorubicin intoxication. The most frequent type of polyneuropathy, namely distal axonopathy with accumulation of axon organelles leading to distal fibre loss, is associated with decrease in amount of the retrograde fast component (rFC). The transport is impaired before the appearance of symptoms and electrophysiological signs of neuropathy develop in the intoxications induced by parabromophenylacetylurea, acrylamide and 2.5 hexanedione, and the severity of neuropathy is proportional to the rFC impairment.

Animals↗
PubMed1994

Phosphorylation-dependent immunoreactivity of neurofilaments and the rate of slow axonal transport in the central and peripheral axons of the rat dorsal root ganglion.

The rate of axonal transport of tubulin, actin, and the neurofilament proteins was measured in the peripheral and central projections of the rat L5 dorsal root ganglion (DRG). [35S]Methionine was injected into the DRG, and the "front" of the radiolabeled protein was located 7, 14, and 20 days postinjection. Transport rates calculated for the neurofilament triplet proteins, tubulin, and actin in the peripheral nerve were approximately 1.5-fold faster than those in the dorsal root. A progressive decrease in the rate of transport was observed from 7 to 20 days after radiolabeling in both the central and peripheral directions (neurofilaments, approximately 1.7-fold; tubulin/actin, 2.1-fold). A surgical preparation, leaving the peripheral sciatic nerve with predominantly sensory fibers, was the basis for ELISAs for phosphorylation-dependent immunoreactivity of the high-molecular-weight neurofilament protein. In both dorsal roots and peripheral sensory axons the degree of phosphorylation was greater in nerve segments further away from the cell bodies. The degree of phosphorylation-related immunoreactivity correlates with the slowing of transport of radiolabeled cytoskeletal protein.

Animals↗
PubMed1990

The effects of intraocular pressure elevation on optic nerve axonal transport in the monkey.

Blockage of axonal transport by intraocular pressure (IOP) elevation was studied quantitatively in monkey eyes, using liquid scintillation counting. After 5 h of IOP elevation (perfusion pressure of 30 mmHg), axonally transported protein was measured in the distal third of each optic nerve, which was divided into superotemporal, inferotemporal, superonasal, and inferonasal portions. The ratio of the amount of radioactive protein in each portion of the optic nerve to that in the whole optic nerve was calculated. In eyes with IOP elevation, the mean ratio for the temporal optic nerve was significantly lower than that for the nasal optic nerve. It appeared that axonal transport was not affected homogenously throughout the optic nerve but was more impaired by the temporal half of the optic nerve following IOP elevation.

Analysis of Variance↗
PubMed1999

Evidence for phosphatidylinositol 4-kinase and actin involvement in the regulation of 125I-beta-nerve growth factor retrograde axonal transport.

The signaling events regulating the retrograde axonal transport of neurotrophins are poorly understood, but a role for phosphatidylinositol kinases has been proposed. In this study, we used phenylarsine oxide (PAO) to examine the participation of phosphatidylinositol 4-kinases in nerve growth factor (NGF) retrograde axonal transport within sympathetic and sensory neurons. The retrograde transport of 125I-labeled betaNGF was inhibited by PAO (0.5-2 nmol/eye), and this effect was diminished by dilution. Coinjection of 2,3-dimercaptopropanol with PAO reduced its ability to inhibit 125I-betaNGF retrograde transport. PAO (20 nM to 200 microM) also inhibited NGF-dependent survival of both sympathetic and sensory neuronal populations. F-actin staining in sympathetic and sensory neuronal growth cones was disrupted by PAO at 10 and 2 nM, respectively, and occurred within 5 min of exposure to the drug. The actin inhibitor latrunculin A also rapidly affected F-actin staining in vitro and reduced 125I-betaNGF retrograde axonal transport in vivo to the same extent as PAO. These results suggest that both phosphatidylinositol 4-kinase isoforms and the actin cytoskeleton play significant roles in the regulation of 125I-betaNGF retrograde axonal transport in vivo.

1-Phosphatidylinositol 4-Kinase↗
PubMed2004

Impaired axonal transport and altered axolemmal permeability occur in distinct populations of damaged axons following traumatic brain injury.

Traumatic axonal injury (TAI) evolves within minutes to hours following traumatic brain injury (TBI). Previous studies have identified axolemmal disruption and impaired axonal transport (AxT) as key mechanisms in the evolution of TAI. While initially hypothesized that axolemmal disruption culminates in impaired AxT, previous studies employed single-label methodologies that did not allow for a full determination of the spatial-temporal relationships of these two events. To explore directly the relationship between impaired AxT and altered axolemmal permeability, the current investigation employed 40, 10, and 3 kDa fluorescently conjugated dextrans as markers of axolemmal integrity, with antibodies targeting the anterogradely transported amyloid precursor protein (APP) utilized as a marker of impaired AxT. Rats underwent impact acceleration TBI and were intrathecally administered 40 kDa, 40 + 10 kDa or 40 + 3 kDa fluorescently tagged dextrans, with brains subsequently prepared for APP immunofluorescence. Brainstem corticospinal tracts (CSpT), medial lemnisci (ML), and medial longitudinal fasciculi were examined for evidence of TAI. APP and all dextrans consistently localized to distinct classes of TAI. Dextrans were noted as early as 5 min following injury within axonal segments demonstrating an irregular/tortuous appearance, and were seen within thin and elongate/vacuolated axons by 30 min-6 h following injury. APP, first noted within swollen axons at 30 min following injury, was found within progressively swollen axons that showed no dextran colocalization within 3 h of injury. However, by 6 h, dextrans colocalized in disconnected axonal bulbs. At this time-point, dextrans also persisted within single-labeled, highly vacuolated/thin, and elongate axons. These studies confirm that axolemmal disruption and impaired AxT occur as distinct non-related events early in the pathogenesis of TAI. Further, these studies provide evidence that the process of impaired axonal transport and subsequent axonal disconnection leads to delayed axolemmal instability, rather than proceeding as a consequence of initial axolemmal failure. This finding underscores the need of multiple approaches to fully assess the axonal response to TBI.

Amyloid beta-Protein Precursor↗
PubMedDate not supplied

Relationships between the rapid axonal transport of newly synthesized proteins and membranous organelles.

Rapid axonal transport is generally viewed as being exactly analogous to the secretory process in nonneuronal cells. The cell biology of rapid axonal transport is reviewed, the central concern being to explore those aspects that do not fit into the general secretory model and which may thus represent specific neuronal adaptations. Particular attention is paid to the relationship between the transport of newly synthesized proteins and of the membranous organelles that act as carriers. Sites in the transport sequence at which the behavior of axonal transport may differ from the secretory model are at the initiation of axonal transport at the trans-side of the Golgi apparatus, within the axon where molecules are deposited from the moving phase to a stationary phase, and at nerve terminals or axonal lesions where transport reversal takes place.

Animals↗
PubMed1992

Experimental diabetic neuropathy. Effect of ganglioside treatment on axonal transport of cytoskeletal proteins.

Abnormalities in axonal transport of proteins are thought to play an important role in the pathogenesis of diabetic neuropathy. Gangliosides exert a positive action on numerous alterations in biochemistry and physiology of diabetic nerves. This study was undertaken to assess the effects of exogenous gangliosides on the axonal transport of structural proteins such as actin and tubulin in the sensory fibers of short-term (9-wk) and long-term (6-mo) diabetic rats. Adult Sprague-Dawley rats were made diabetic with a single injection of 70 mg/kg streptozocin i.p. Subgroups were injected daily with either highly purified ganglioside mixture (10 mg/kg i.p.) or saline for 1 mo, beginning either 2 or 17 wk after streptozocin injection. Age-matched rats were used as controls. Axonal transport was studied by the pulse-labeling technique. Three weeks after labeling, sciatic nerves were dissected out and processed for sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. In diabetic rats of both experimental designs, the transport rate of tubulin and actin was decreased by approximately 30% compared with control rats. Ganglioside treatment counteracted such alterations in both 9-wk and 6-mo diabetic rats. These data suggest a pharmacological effect that could be correlated with molecular interactions between integral membrane glycolipids and cytoskeletal elements.

Actins↗