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Motors for fast axonal transport.

In neurons and other animal cells, membrane-bound vesicles course rapidly along cytoskeletal filaments to reach their destinations. Based on a variety of in vivo studies it is becoming clear that the microtubule-based motor, kinesin (and its relatives), drive vesicle movements in axons. Surprisingly, some axonal membranes have the capacity to move on both microtubules and actin filaments.

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Glycoproteins of axonal transport: polypeptides interacting with the lectin from Aleuria aurantia.

The interaction between a new fucose-specific lectin from Aleuria aurantia and brain glycoproteins is described. It was found that several different glycoproteins could bind to a column of immobilized Aleuria lectin and that the bound material could be eluted with low concentrations of L-fucose. The polypeptide pattern of the bound glycoproteins differed markedly from that of unbound glycoproteins. A major portion of rapidly transported fucose-labelled glycoproteins from retinal ganglion cells bound to the Aleuria lectin. This chromatographic procedure led to a considerable purification of the rapidly transported glycoproteins. The major labelled, rapidly transported polypeptide which bound to the Aleuria lectin had an apparent mol. wt. of 114,000.

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Reversible blockade of retrograde axonal transport in the rat sciatic nerve by vincristine.

Altered axoplasmic transport has been implicated as a contributing factor in neuropathic pain states. Treatments which produce transient axoplasmic transport blockade have shown initial promise as therapeutic procedures in the management of chronic neuropathic pain. The present study evaluated the capacity of the vinca alkaloid, vincristine to produce reversible blockade of retrograde axoplasmic transport. Results indicated that intraneural administration of 10(-5)M vincristine resulted in blockade of retrograde axoplasmic transport of [3H]leucine 24 h following administration. Importantly, the effect reversed over the next four days and axoplasmic transport was re-instated fully at day five. The implications of these results are discussed in relation to the potential use of axoplasmic transport blocking agents in the management of chronic neuropathic pain.

Animals↗

Anterograde axonal transport of internalized GDNF in sensory and motor neurons.

Endogenous glial cell line-derived neurotrophic factor (GDNF) has been shown to be anterogradely transported in sensory and motor neurons which do not express detectable levels of GDNF mRNA. The source of the anterograde axonal GDNF in these neurons has remained unclear. Here we show that radiolabeled GDNF is internalized by dorsal root ganglion (DRG) and hypoglossal motor neurons at their cell bodies and/or their dendrites and that a mechanism exists to transport the internalized GDNF anterogradely in their axons. Since adjacent glial cells express GDNF mRNA, these data support the concept that Schwann cell- or oligodendrocyte-derived GDNF is taken up by DRG and motor neurons, respectively, and transported anterogradely along the axons for release from terminals, resulting in neuronal transcytosis.

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Distribution of pressure-induced fast axonal transport abnormalities in primate optic nerve. An autoradiographic study.

The distribution of transport abnormalities in primate optic nerve from eyes subjected to five hours of pressure elevation (perfusion pressure of 35 mm Hg) was studied. Tissue autoradiography and electron microscopy were used to localize regions of the lamina cribrosa with increased transport interruption. A preferential involvement by this transport abnormality involved the superior, temporal, and inferior portions, to the exclusion of the nasal portion, of the optic nerve head. This observation supports the hypothesis that transport interruption seen in this model may be pertinent to the study of clinical glaucomatous neuropathy.

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Simultaneous immunohistochemical demonstration of intra-axonally transported markers and neuropeptides in the peripheral nervous system of the guinea pig.

Projections and peptide neurotransmitter/neuromodulator content of autonomic and visceral afferent neurons of the guinea pig were studied after application of the subunit B of cholera toxin (CTB) with or without horseradish peroxidase (HRP) as retrograde and anterograde tracers and subsequent immunohistochemical processing for double staining using antibodies raised to CTB, HRP and various neuropeptides. The results demonstrate that substance P (SP)- and calcitonin gene-related peptide (CGRP)-containing dorsal root ganglion cells project to the pylorus as well as to the celiac superior mesenteric and stellate ganglia as demonstrated with both retrograde and anterograde transport methodology. Binding studies revealed that a small number of the CTB-binding dorsal root ganglion cells contains immunoreactivity to SP and CGRP. The majority of the CTB-binding cells is SP- and CGRP-negative and terminate in the deeper parts of the dorsal horn. After injection of CTB conjugated to HRP (B-HRP) into the nodose ganglion, both motor and sensory elements were labeled in the medulla oblongata. Some of the CTB labeled vagal sensory nerve fibers in the nucleus tractus solitarii (NTS) were also found to contain immunoreactivity to SP or CGRP. The tracer was also transported through the peripheral branch of the nodose ganglion cells and labeled terminals in the esophagus.

Animals↗

The anterograde and retrograde axonal transport of biotinylated dextran amine and biocytin in the nervous system of teleosts.

Biotinylated dextran amine (BDA) and biocytin are well transported both retrogradely and anterogradely. Both tracers have stable molecular structure for long-term storage and examination, and their visualizations can be realized by simple histochemical reactions. Therefore, the BDA and biocytin are widely used in neuroanatomical studies as the tract-tracing markers. The results obtained by BDA and biocytin applications to various areas of the nervous system in teleosts were qualitatively identical, and the retrogradely and anterogradely labeled structures could be clearly identified with reference to the counter-staining. Iontophoretic injections or crystal insertions resulted in filling of cell bodies, dendrites and terminals in the core of injection side, revealing morphological details of the local and distant somata, dendritic arborizations and axonal terminals. However, biocytin exhibited superior to BDA in anterograde transport, and could label very thin axons, axonal collaterals and terminal ramifications. In contrast, retrograde transport of BDA was superior to that of biocytin, and resulted in more complete dendritic filling of retrograde labeled neurons including dendritic arborizations and spines.

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Anterograde axonal transport of horseradish peroxidase in the rat postganglionic sympathetic nerves.

Seven minutes after initiating the experiment, horseradish peroxidase (HRP)-labeled pinocytotic vesicles were observed on the plasma membranes of the postganglionic sympathetic neurons in the left superior cervical ganglia (SCG). HRP reaction product was also demonstrated in the vesicles of the smooth endoplasmic reticulum (sER) and multivesicular bodies in the neuronal perikarya. The HRP-positive vesicles of sER and multivesicular bodies were also detected in the adrenergic sympathetic nerve endings in the pineal gland 7 minutes after initiation of the experiment. This suggests that the HRP is rapidly transported anterogradely from the postganglionic sympathetic neurons in the SCG into the axon terminals in the pineal glands through the vesicles of the sER and multivesicular bodies. The present findings reveal that the rate of anterograde transport of HRP is 85 mm/h and that the majority of the adrenergic sympathetic nerves in either the left or right half of the pineal gland are derived from the postganglionic sympathetic neurons in both the left and right superior cervical ganglia.

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