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At least 1,207 records · Page 67Linked to original sources
PubMed1977

Axonal transport of [3H]fucosyl glycoproteins in noradrenergic neurons in the rat brain.

The transport of [3H]fucosyl glycoproteins has been investigated in the noradrenergic pathway from the locus coeruleus (LC) to the hypothalamus in the rat brain by use of local injection of L-[6-3H]fucose into the LC. Two discrete waves of 3H-glycoprotein pass through the hypothalamus in a caudorostral direction traveling at 4 mm/h (96 mm/day) and 2 mm/h (48 mm/day) respectively. Both waves appear to originate from the LC at approximately 2 h after the injection of [3H]fucose, a time when incorporation into glycoprotein has not yet peaked in the LC. Lesioning the LC-hypothalamic pathway with 6-OHDA, but not carrier solution, blocks both waves of 3H-glycoprotein demonstrating that transport occurs exclusively in the catecholamine axons within the pathway. DEAE-Sephadex chromatography combined with 6-OHDA lesions demonstrates clear differences in the character of 3H-glycoproteins in the two waves undergoing transport. The relative lack of labelling of hypothalamic glycoproteins in the interval before and after these waves suggests that relatively few rapidly transported glycoproteins contribute to the non-terminal axon membrane and are probably primarily transported to the nerve terminal. No evidence for slow axoplasmic transport of [3H]fucosyl glycoproteins is found.

Adrenergic Fibers↗
PubMed1996

Ca2+/calmodulin-dependent protein kinase type IV in dorsal root ganglion: colocalization with peptides, axonal transport and effect of axotomy.

Using the indirect immunofluorescence technique, the distribution of Ca2+/calmodulin-dependent protein kinase IV (CaM kinase IV) was studied in dorsal root ganglia (DRGs) and the sciatic nerve under normal circumstances and after axotomy and nerve ligation. CaM kinase IV-like immunoreactivity (-LI) was observed mainly in small DRG neurons but also in some large ones with the immunoreactivity mainly confined to the cell nuclei and with varying levels in the cytoplasm. CaM kinase IV-LI was present in around 1/4 of all CGRP-positive neurons and in the vast majority of the somatostatin-positive neurons. The enzyme levels decreased markedly after axotomy. The enzyme was also observed in axons in the sciatic nerve and accumulated both proximal and distal to a ligation. The present results suggest that CaM kinase is not of direct importance for upregulation of neuropeptides in DRG neurons after nerve injury. In addition to a nuclear function it may also play a role in the peripheral processes of DRG neurons.

Animals↗
PubMed1978

[Demonstration of the neurosecretory hypothalamo-rhombencephalic junction in rats by the retrograde axonal transport of horseradish peroxidase].

The retrograde transport of horseradish peroxidase (HRP) was used to demonstrate the neurosecretory hypothalamo-hindbrain connection of the rat. Following HRP injections into the region of the dorsal columns nuclei labeled cells were observed in the caudal part of the paraventricular nucleus and in the lateral hypothalmic area. Hypothalamo-hindbrain projections are predominantly uncrossed.

Animals↗
PubMedDate not supplied

Neuronal compartments and axonal transport of synapsin I.

Studies on the transport kinetics and the posttranslational modification of synapsin I in mouse retinal ganglion cells were performed to obtain an insight into the possible factors involved in forming the structural and functional differences between the axon and its terminals. Synapsin I, a neuronal phosphoprotein associated with small synaptic vesicles and cytoskeletal elements at the presynaptic terminals, is thought to be involved in modulating neurotransmitter release. The state of phosphorylation of synapsin I in vitro regulates its interaction with both synaptic vesicles and cytoskeletal components, including microtubules and microfilaments. Here we present the first evidence that in the mouse retinal ganglion cells most synapsin I is transported down the axon, together with the cytomatrix proteins, at the same rate as the slow component b of axonal transport, and is phosphorylated at both the head and tail regions. In addition, our data suggest that, after synapsin I has reached the nerve endings, the relative proportions of variously phosphorylated synapsin I molecules change, and that these changes lead to a decrease in the overall content of phosphorus. These results are consistent with the hypothesis that, in vivo, the phosphorylation of synapsin I along the axon prevents the formation of a dense network that could impair organelle movement. On the other hand, the dephosphorylation of synapsin I at the nerve endings may regulate the clustering of small synaptic vesicles and modulate neurotransmitter release by controlling the availability of small synaptic vesicles for exocytosis.

Animals↗
PubMed1986

Influence of translocation track on the motion of intra-axonally transported organelles in human nerve.

The mechanism by which organelles are transported bidirectionally in axoplasm is still unknown; however, evidence of a key role for microtubules in many nonmammalian models has been established. We have observed common or shared tracks within the axoplasm of human nerves along which multiple organelles of varying size and shape are bidirectionally transported. Organelles traveling anterogradely and retrogradely were visualized by video-enhanced differential interference contrast optics and analyzed with the aid of computer-image-processing techniques. Speeds of translocating organelles were determined at eight to 16 translocation points along a path or "track." Each translocation speed was plotted against its corresponding position on the track to develop a "speed/position diagram." Regardless of mean organelle speed or direction of motion, organelles sharing a common track exhibited similar patterns of "speeding up" and "slowing down" relative to position along the track. Speed position data for organelles translocating the local axonal region of a common track showed no unique patterns (not different from a uniform distribution, p less than 0.05). The unique speed/position patterns exhibited by common tracks were not necessarily related to the patterns of other tracks in the immediate vicinity (distance between tracks of less than 0.50 micron). These findings suggest that there are "common tracks" shared by organelles moving retrogradely and anterogradely; both the organelles and the "track" associated with its translocation play a role in the resultant motion of that organelle; the influence exerted by a common track on the motion of an organelle results in a pattern of speed changes related to position along the track.

Afferent Pathways↗
PubMed1982

Evidence that all newly synthesized proteins destined for fast axonal transport pass through the Golgi apparatus.

Effects of the sodium ionophore, monensin, were examined on the passage from neuronal cell body to axon of materials undergoing fast intracellular transport. In vitro exposure of bullfrog dorsal root ganglia to concentrations of drug less than 1.0 micron led to a dose-dependent depression in the amount of fast-transported [3H]leucine- or [3H]glycerol-labeled material appearing in the nerve trunk. Incorporation of either precursor was unaffected. Exposure of a desheathed nerve trunk to similar concentrations of monensin, while ganglia were incubated in drug-free medium, had no effect on transport. With [3H]fucose as precursor, fast transport of labeled glycoproteins was depressed to the same extent as with [3H]leucine; synthesis, again, was unaffected. By contrast, with [3H]galactose as precursor, an apparent reduction in transport of labeled glycoproteins was accounted for by a marked depression in incorporation. The inference from these findings, that monensin acts to block fast transport at the level of the Golgi apparatus, was supported by ultrastructural examination of the drug-treated neurons. An extensive and selective disruption of Golgi saccules was observed, accompanied by an accumulation of clumped smooth membranous cisternae. Quantitative analyses of 48 individual fast-transported protein species, after separation by two-dimensional gel electrophoresis, revealed that monensin depresses all proteins to a similar extent. These results indicate that passage through the Golgi apparatus is an obligatory step in the intracellular routing of materials destined for fast axonal transport.

Animals↗
PubMed1983

Simultaneous visualization of Nuclear yellow and iron-dextran complex for demonstration of branched neurons by retrograde axonal transport.

Retrogradely transported iron-dextran complex and Nuclear yellow could be demonstrated simultaneously on the same sections of rat CNS. Using combined bright-field and ultraviolet illuminations, double labeled neurons were observed. They exhibited a fluorescent nucleus and cytoplasmic Prussian blue granules. Thus, the combination of these two tracers appeared to be a convenient method for the anatomical demonstration of collaterals.

Animals↗
PubMed1992

Emulsifier for intravenous cyclosporin inhibits neurite outgrowth, causes deficits in rapid axonal transport and leads to structural abnormalities in differentiating N1E.115 neuroblastoma.

The emulsifier for cyclosporin in clinical i.v. formulations, Cremophor EL, has recently come into question as a possible source of neurotoxic side effects in immunosuppressant therapy. To address this issue we tested Cremophor EL and cyclosporin on an in vitro neuronal model, the differentiating N1E.115 neuroblastoma cell. In terms of effects on elaboration of neurites by these cells, Cremophor accounted for nearly all the neurotoxicity of clinically formulated cyclosporin. At a concentration of 0.005% (v/v), Cremophor EL halved the number of cells that extended neurites after 48 hr in serum-free medium. Average neurite length was also reduced substantially. Inhibition of neurite outgrowth first became apparent 24 hr after exposure to Cremophor EL. Neurites that did grow in the presence of Cremophor were disfigured by a series of regularly spaced, gross dilatations (beads) filled with large (0.2-0.5 microns) lipid vesicles. Abnormalities of rapid axonal transport were documented in the beaded neurites by means of video-enhanced contrast, differential interference-contrast microscopy. Velocity of retrograde transport remained normal, but the velocity of anterograde transport and the total bidirectional flux of organelles were both reduced. It seems likely that the inhibition of neurite outgrowth, the swellings of the neurites and the abnormalities of transport are interrelated phenomena.

Animals↗
PubMed1989

Toxic neurofilamentous axonopathies and fast anterograde axonal transport. I. The effects of single doses of acrylamide on the rate and capacity of transport.

Acrylamide (ACR) produces a neuropathy in the central and peripheral nervous systems characterized by neurofilament-containing swellings in the distal nerve and eventual dying-back degeneration of axons. The effects of a single exposure to ACR on the rate and quantity of protein transported in the rat sciatic nerve has been measured to determine whether fast axonal transport is compromised by this toxicant. Using the segmental analysis of radioactive label of proteins following 3H-leucine injections into the DRG, ACR (50-100 mg/kg) significantly reduced the rate of fast anterograde transport by 9.3 to 20.8% but, more importantly, reduced the quantity of transported protein by 42.4 to 51.3%. The non-neurotoxic analogue methylene bis-acrylamide did not significantly change either parameter. The reductions in transport were not due to general effects of the toxicant upon protein synthesis. Therefore, fast anterograde transport was significantly affected by a single exposure to ACR in the same magnitude as retrograde transport. Discovery of these dramatic changes was due to differences from previous studies in the time frame of study of transport in relation to toxicant injection and to measurements of the quantity of protein transported rather than only the rate. These changes may be significant in terms of the pathogenesis of distal nerve degeneration.

Acrylamides↗
PubMed1992

Immunohistochemical localization of the D1 dopamine receptor in rat brain reveals its axonal transport, pre- and postsynaptic localization, and prevalence in the basal ganglia, limbic system, and thalamic reticular nucleus.

D1 dopamine receptor localization was examined by immunohistochemistry using a polyclonal anti-peptide antibody which (i) immunoprecipitated a protein fragment encoded by a D1 receptor cDNA and (ii) on Western blots of solubilized striatal and hippocampal membranes recognized two proteins of approximately 50 kDa and 75 kDa, corresponding to reported sizes of D1 receptor proteins. Immunoreactivity overlapped with dopamine-containing pathways, patterns of D1 receptor binding, and mRNA expression. Staining was concentrated in prefrontal, cingulate, parietal, piriform, entorhinal, and hippocampal cortical areas and subcortically in the basal ganglia, amygdala, septal area, substantia inominata, thalamus, hypothalamus, and neurohypophysis. Prominent labeling was seen in the thalamic reticular nucleus, a region known to integrate ascending basal forebrain inputs with thalamocortical and corticothalamic pathways and in fiber bundles interconnecting limbic areas. In striatal neuropil, staining appeared in spines (heads and necks), at postsynaptic sites in dendrites, and in axon terminals; in the pars reticulata of the substantia nigra, labeling was prevalent in myelinated and unmyelinated axons and dendrites. These data provide direct evidence for the regional and subcellular distribution of D1 receptor protein in the brain and for its pre- and postsynaptic localization in the basal ganglia. The prominent immunoreactivity seen in the limbic system and thalamic reticular nucleus supports an important role for this receptor subtype in mediating integrative processes involved with learning, memory, and cognition.

Animals↗
PubMed1999

Hypothalamopontine projections in the rat: anterograde axonal transport studies utilizing light and electron microscopy.

Projections to the basilar pontine nuclei (BPN) from a variety of hypothalamic nuclei were traced in the rat utilizing the anterograde transport of biotinylated dextran amine. Light microscopy revealed that the lateral hypothalamic area (LH), the posterior hypothalamic area (PH), and the medial and lateral mammillary nuclei (MMN and LMN) are the four major hypothalamic nuclei that give rise to labeled fibers and terminals reaching the rostral medial and dorsomedial BPN subdivisions. Hypothalamopontine fibers extended caudally through the pontine tegmentum dorsal to the nucleus reticularis tegmenti pontis and then coursed ventrally from the main descending bundle toward the ipsilateral basilar pontine gray. Some hypothalamopontine fibers crossed the midline in the tegmental area just dorsal to the pontine gray to terminate in the contralateral BPN. Electron microscopy revealed that the ultrastructural features of synaptic boutons formed by axons arising in the LH, PH, MMN, and LMN are similar to one another. All labeled hypothalamopontine axon terminals contained round synaptic vesicles and formed asymmetric synaptic junctions with dendritic shafts as well as dendritic appendages, and occasionally with neuronal somata. Some labeled boutons formed the central axon terminal in a glomerular synaptic complex. In summary, the present findings indicate that the hypothalamus projects predominantly to the rostral medial and dorsomedial portions of the BPN which, in turn, provide input to the paraflocculus and vermis of the cerebellum. Since the hypothalamic projection zones in the BPN also receive cerebral cortical input, including limbic-related cortex, the hypothalamopontine system might serve to integrate autonomic or limbic-related functions with movement or somatic motor-related activity. Alternatively, since the cerebellum also receives direct input from the hypothalamus, the BPN may function to provide additional somatic and visceral inputs that are used by the cerebellum to perform the integrative function.

Animals↗
PubMed1988

Deposition and transfer of axonally transported phospholipids in rat sciatic nerve.

Radioactive glycerol, ethanolamine, or choline injected into the vicinity of the cell bodies of rat sciatic nerve sensory fibers is incorporated into phospholipid. Some newly synthesized ethanolamine and choline phosphoglycerides are subsequently committed to transport down the sciatic nerve axons at a rate of several hundred millimeters per day. Most labeled choline phosphoglycerides move uniformly down the axons; in contrast, the crest of moving ethanolamine phosphoglycerides is continually attenuated. These data, as well as differences in the clearance of these phospholipids distal to a nerve ligature, suggest that various classes of labeled phospholipids are differentially unloaded from the transport vector (possibly by exchange with unlabeled lipid in stationary axonal structures) during movement down the axons. The extent of unloading appears to be defined by the base moiety; both diacyl and plasmalogen species of ethanolamine phosphoglycerides exchange extensively with stationary axonal lipids, while most choline phosphoglycerides continue down the axons. Autoradiographic studies with 3H-choline and 3H-ethanolamine demonstrated that most unloaded phospholipid is initially deposited in axonal structures; some of this unloaded lipid is subsequently transferred to the axon/myelin interface (axolemma?) and then to myelin. Although transported ethanolamine phosphoglycerides exchange more extensively with lipids in stationary axonal structures than do choline phosphoglycerides, at early times more label from 3H-choline is found in myelin. A model to resolve this seeming discrepancy is proposed, wherein a differential topographic localization of phospholipid classes in the membrane of the transport vector allows for a preferential extensive exchange of transported ethanolamine phosphoglycerides with lipids in stationary axonal structures, while choline phosphoglycerides become available for rapid transfer to myelin by a process involving vesicle fusion with axolemma.

Animals↗
PubMedDate not supplied

Uptake and retrograde axonal transport of horseradish peroxidase in normal and axotomized motor neurons during postnatal development.

The axonal uptake and somatopetal transport of horseradish peroxidase (HRP) was studied during early postnatal development of facial neurons in mice and rats. HRP injected systemically or locally into the muscles of the vibrissae, diffused into the region of the immature neuromuscular junction and was incorporated into vesicles in the axon terminals on the first and third postnatal days, at a time when synaptic vesicles were already present. HRP later was found in the nerve cell bodies of the facial nucleus in the brain stem indicating a somatopetal transport of the tracer in axons. The response of facial neurons to nerve transection changed from rapid neuronal death to prolonged survival between the 6th and 10th postnatal day. HRP was transferred to nerve cell bodies after topical application to the proximal stump of transected facial nerves in rats 3 days-of-age. In the perikaryon it was localized to vesicles and vacuoles with no signs of leakage into the cytoplasm. In the light of our findings different hypotheses for the mechanism of the neuronal death in the immature animals are discussed.

Aging↗
PubMed1987

[125I] triiodothyronine in the rat brain: evidence for neural localization and axonal transport derived from thaw-mount film autoradiography.

Previous thaw-mount light microscopic autoradiographic studies have shown that intravenously administered [125I] triiodothyronine is saturably concentrated and retained for at least 10 hours in discrete neural systems in the rat brain. To survey the brain more completely and to gain information about the time course of labeling, serial thaw-mount film autoradiograms were prepared from rat brains obtained at intervals through 48 hours after intravenous injection of high specific activity [125I] triiodothyronine. Parallel biochemical studies of whole brain homogenate extracts revealed that, at all time intervals, the label in the brain was mainly due to triiodothyronine itself (80%), or other organic iodocompounds (15%), but probably not due to free [125I] iodide (3%), which is rapidly transported out of the brain. The highly reproducible, well-defined labeling patterns seen on film indicated a widespread but selective localization of the hormone. At early times after intravenous injection of [125I] triiodothyronine, label was nonuniformly and prominently concentrated in selected regions of gray matter; evidence for saturability of hormone processing was obtained in competition studies with unlabeled triiodothyronine. Discrete labeling of fiber tracts (usually after 10 hours) left some regions of white matter conspicuously unlabeled. At 48 hours, many originally labeled gray regions showed markedly diminished or virtually complete loss of radioactivity, whereas others became newly or more prominently labeled. At that time, certain fiber tracts were also conspicuously labeled. The observed changing profiles of regional labeling over time are best explained by movement of the hormone from original sites of saturable incorporation in specific nuclei, to terminal fields, through the mechanism of axonal transport.

Amygdala↗
PubMed1992

Neurotensin increases tyrosine hydroxylase messenger RNA-positive neurons in substantia nigra after retrograde axonal transport.

In previous studies we have shown that labelled neurotensin injected into the rat striatum was found to be transported retrogradely in dopaminergic neurons through a process which was receptor and microtubule dependent. Now, we show, by in situ hybridization, the consequences of the striatal injection of neurotensin on the gene expression of tyrosine hydroxylase in the substantia nigra. Rats were injected with neurotensin or its fragments in the striatum of one side and with saline or the inactive fragment on the other. The number of nigral cells expressing tyrosine hydroxylase mRNA was found to increase by 40% after injection of neurotensin or its active fragment (neurotensin 8-13). In the same experimental conditions, the inactive fragment (neurotensin 1-8) was without effect. Time-course experiments revealed that the tyrosine hydroxylase mRNA was increased 4 h after neurotensin injection but not at 1 or 16 h. The fact that the increase of mRNA parallels the appearance of labelled neurotensin in the substantia nigra indicates that the changes in the gene expression of tyrosine hydroxylase might be the consequence of the retrograde axonal transport of neurotensin. These results represent the first evidence for the existence of a long-distance retrograde signalling process in which the neuropeptide and presumably its receptor may serve as information molecule between synapses and the cell body.

Animals↗
PubMed1980

Effect of chronically administered nicotine on axonal transport of dopamine-beta-hydroxylase in peripheral adrenergic neurons and on blood pressure and heart rate in the rat.

Nicotine was given to rats of about 200 g b.wt. in the drinking water for up to 2 months. Different doses of nicotine, from 25 mg to 100 mg per litre water, were tested with respect to their reducing effect on the normal increase in body weight. No effect was found on the normal accumulation of dopamine-beta-hydroxylase (DBH) proximal to a ligation of peripheral adrenergic neurons. This indicated a normal turnover of amine storage granules. This was interpreted as nicotine being without effects on the activity of the adrenergic neurons. In agreement with this lack of effect no changes of blood pressure or heart rate were found in rats receiving 50 mg nicotine per litre of drinking water.

Animals↗
PubMed1980

Potassium stimulated release of axonally transported radioactivity from slices of rabbit superior colliculus.

The radioactivity in the trichloroacetic acid (TCA) soluble pool in the terminals of the retinal ganglion cells in the superior colliculus (SC) was studied one month after labelling of the nerve cell bodies in the retina with different radioactive amino acids. The TCA soluble fraction in the SC represented a few per cent of the total radioactivity of the isolated tissue and was mainly derived from protein degradation. The perfused slice of the SC responded to high K+ depolarization with an increased release of TCA-soluble radioactivity, while small changes occurred for TCA-precipitable fractions. The evoked release of TCA-soluble radioactivity was particularly prominent after labelling with [3H]glycine. The release was Ca2+-dependent and the response to repetitive depolarization indicated a continuous replenishment of the releasable pool.

Amino Acids↗
PubMed1984

Olivary projections from the pretectal region in the cat studied with horseradish peroxidase and tritiated amino acids axonal transport.

The organization of the projection from the pretectal region to the inferior olive in the cat was studied with autoradiographic and horseradish peroxidase (HRP) methods. After injections of HRP into the olive in six cats, cells were labeled ipsilaterally in the anterior pretectal nucleus (NPA), the posterior pretectal nucleus (NPP), the nucleus of the optic tract (NOT), and the dorsal terminal nucleus of the accessory optic tract (DTN). In three experiments, tritiated amino acids were injected into those parts of the pretectal region which contained labeled cells in the HRP experiments, and the projections to the olive were plotted. Both NPA and NPP projected to the rostral half of the dorsal accessory olive, the rostromedial margin of the ventral lamella, and the lateral part of the ventrolateral outgrowth. NOT projected to the caudal half of the dorsal cap, while DTN projected to both the dorsal cap and nucleus beta. The projections are entirely ipsilateral.

Amino Acids↗