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Trajectories of regenerating retinal axons in the goldfish tectum: I. A comparison of normal and regenerated axons at late regeneration stages.

To visualize and compare the intratectal path of normal and regenerated retinal axons, HRP was applied to localized sites in the dorsotemporal and dorsonasal retina in normal goldfish and in goldfish at 3-12 months after optic nerve section. The anterogradely labeled axons were traced in tectal whole mounts. In normal animals the axons were confined to the appropriate ventral hemitectum. Therein they ran in very orderly routes (Stuermer and Easter: J. Neurosci. 4:1045-1051, '84) and terminated in regions retinotopic to the labeled ganglion cells in the retina. The terminal arbors of dorsotemporal axons resided in the ventrorostral tectum and those of dorsonasal axons in the ventrocaudal tectum. In regenerating animals the terminal arbors also resided at retinotopic regions, where they sometimes formed two separate clusters. In contrast to normal axons, the regenerating ones traveled in abnormal routes through the appropriate and inappropriate hemitectum. From various ectopic positions, they underwent course corrections to redirect their routes toward the retinotopic target region. In their approach toward their target sites, dorsotemporal and dorsonasal axons behaved differently in that the vast majority of dorsotemporal axons coursed over the more rostral tectum whereas dorsonasal axons progressed into the caudal tectal half. This differential behavior of regenerating dorsonasal and dorsotemporal axons was substantiated by a quantitative evaluation of axon numbers and orientations.

Animals↗

Trajectories of regenerating retinal axons in the goldfish tectum: II. Exploratory branches and growth cones on axons at early regeneration stages.

HRP was applied to small sites in the dorsotemporal or dorsonasal retina in fish at 10-36 days after optic nerve section. The anterogradely labeled axons were visualized in tectal whole mounts. Axons traveled through all regions of the tectum in various abnormal routes. Misrouted axons were also seen to alter their orientation and to direct their course toward their target. At all regeneration stages the majority of dorsotemporal axons coursed and achieved target-related orientations preferentially within the rostral tectal half whereas dorsonasal axons proceeded into the caudal tectum. The growing axons exhibited various morphologies. All axons in the superficial fascicle layer stratum opticum (SO) and some in the synaptic layer stratum fibrosum et griseum superficiale (SFGS) were unbranched and tipped with a leading growth cone. Other axons in the synaptic layer carried one to several growth cones at their ends and often filopodia proximal to the growth cone, or they had sprouted numerous side branches with growth cones and filopodia on the shaft and on branches. Some axons at retinotopic or ectopic sites gave rise to several long branches of several hundred microns in length, with growth cones and filopodia. From 32 days onward axons ending in terminal arbors at retinotopic sites became apparent. Thus, numerous axons at early regeneration stages go through a phase of exploratory growth on their way toward their target sites.

Animals↗

Retinal axon growth cones respond to EphB extracellular domains as inhibitory axon guidance cues.

Axon pathfinding relies on cellular signaling mediated by growth cone receptor proteins responding to ligands, or guidance cues, in the environment. Eph proteins are a family of receptor tyrosine kinases that govern axon pathway development, including retinal axon projections to CNS targets. Recent examination of EphB mutant mice, however, has shown that axon pathfinding within the retina to the optic disc is dependent on EphB receptors, but independent of their kinase activity. Here we show a function for EphB1, B2 and B3 receptor extracellular domains (ECDs) in inhibiting mouse retinal axons when presented either as substratum-bound proteins or as soluble proteins directly applied to growth cones via micropipettes. In substratum choice assays, retinal axons tended to avoid EphB-ECDs, while time-lapse microscopy showed that exposure to soluble EphB-ECD led to growth cone collapse or other inhibitory responses. These results demonstrate that, in addition to the conventional role of Eph proteins signaling as receptors, EphB receptor ECDs can also function in the opposite role as guidance cues to alter axon behavior. Furthermore, the data support a model in which dorsal retinal ganglion cell axons heading to the optic disc encounter a gradient of inhibitory EphB proteins which helps maintain tight axon fasciculation and prevents aberrant axon growth into ventral retina. In conclusion, development of neuronal connectivity may involve the combined activity of Eph proteins serving as guidance receptors and as axon guidance cues.

Animals↗

Lysosomal activity in developing cat alpha-motor axons under normal conditions and during retrograde axonal transport of horseradish peroxidase.

The occurrence of acid phosphatase (AcPase)-positive bodies, i.e., lysosomes, in lumbosacral alpha-motor axons of kittens, 0-16 weeks of age, was analyzed by light and electron cytochemical methods under normal conditions and after intramuscular injection of horseradish peroxidase (HRP). Axonal lysosomes were rare early postnatally. In 3-week-old animals, a few AcPase-positive bodies appeared in the axoplasm at some nodes of Ranvier in the peripheral nervous system (PNS) and internodally in the intrafunicular motor axon parts within the central nervous system (CNS). From 6 weeks postnatally, a nodal concentration of AcPase-positive bodies was also noted in the CNS. The number of AcPase-positive bodies continued to increase gradually in the course of neuronal maturation. In 16-week-old animals, axonal AcPase activity was still at considerably lower levels than at adult stages. At all ages, acid hydrolase-containing organelles were most commonly found at ventral root nodes. After injection of HRP in the medial gastrocnemius muscle, accumulations of AcPase-positive bodies were seen in the axoplasm at some PNS nodes of the HRP-injected sides of kittens aged 8, 12, and 16 weeks. Incubation for demonstration of both HRP and AcPase activity showed that some organelles at HRP-transporting nodes contained both types of reaction product. The nodal AcPase activity in the intrafunicular, CNS parts of alpha-motor axons of the HRP-exposed sides did not differ from that of the contralateral, uninjected sides. In view of our previous observations in alpha-motor neurons of adult cats in which a lysosome-mediated degradation of axonally transported materials may take place at PNS nodes of Ranvier, the present study illuminates possible differences in the ability to interfere with axonal transport between developing and mature neurons. The infrequent presence of lysosomes in developing alpha-motor axons and the implied disability of their nodal regions to interfere with axonally transported constituents in a way similar to that seen in adult animals may be of significance in that trophic and chemical signals can pass unhindered between the periphery and perikaryon. However, this could also have negative consequences for the vulnerable immature neuron in that various materials retrieved at the axon terminals outside the CNS are permitted a more-or-less free access to the perikaryon.

Aging↗

Growth of lobster giant axons: correlation between conduction velocity and axon diameter.

The conduction velocity and axon diameter of medial and lateral giant axons in lobsters was followed during growth from early juvenile (13 mm) to adult (250 mm) forms. In both axons, conduction velocity increased more than 4-fold in the growth period examined. Correlated with the increase in conduction velocity is an increase in axon diameter and the relationship between these two parameters is expressed by the equation CV = krX, where X equals 0.5 for the lateral and 0.7 for the medial giant axons. The sheath surrounding the giant axons also increases in size during growth with that of the medial giant axon being considerably thicker than that of the lateral giant axon. The significance of the increase in axon diameters is to increase conduction velocity and thereby reduce the latency of the escape response mediated by these giant axons.

Animals↗

Axons connecting somata and axon terminals of luminosity-type horizontal cells in the turtle retina: receptive field studies and intracellular injections of HRP.

Luminosity (L)-type horizontal cell responses to small and large spots of light in the turtle (Geoclemys) retina were recorded intracellularly, and each cell so studied was filled with horseradish peroxidase (HRP) by ionophoretic injection. Following histochemical reaction of the HRP with diaminobenzidine (DAB), light microscopic inspection demonstrated that this type of horizontal cell has a cell body connected to a tuberous axon terminal by a fine axon. By examining the location of the cell in relation to the linear array of electrode penetrations in each preparation, it was possible to determine whether a given recording was made in the cell body or in the axon terminal. The size of the receptive field of the cell body was significantly smaller than that of the axon terminals. Although the center-to-center distances between the cell body and the axon terminal of some L-type horizontal cells were as short as 50 micron, the length of the intervening axon was invariably longer and was at least 250 micron. Unless signals are amplified by some active mechanisms during their propagation along the axon, it is unlikely that current generated in the cell body spreads to the axon terminal through the thin axon, or in the opposite direction. The difference in receptive field sizes of cell body and of axon terminal may therefore indicate that these two structural subunits are electrically isolated.

Animals↗

Axonal sprouting and frank regeneration in the lizard tail spinal cord: correlation between changes in synaptic circuitry and axonal growth.

In our previous studies, we found that the number of supraspinal neurons projecting to the level of tail spinal cord increases by 74% during tail regeneration and that the number of local spinal neurons with descending projections increases 233%. However, only a small fraction of the supraspinal axons (less than 4%) and half of the local spinal axons actually enter the regenerated spinal cord. We suggested that this may be the result of "synaptic capture" in which regrowing axons make synapses on denervated targets rostral to the transection, aborting further regeneration. To examine this hypothesis, morphometric analysis of electron microscope (EM) photomontages was used to test for changes in synaptic distribution on ventral horn neurons rostral to regenerating tail spinal cord. In addition, 3H-thymidine and retrograde markers were used to determine whether the regenerate axons arose from cut axons, neurogenesis, or sprouting from uninjured neurons. 3H-thymidine injections during regeneration, combined with retrograde HRP pathway tracing, did not reveal the production of new neurons in the tail spinal cord. To test whether cut axons regenerate, fluorescein isothiocyanate conjugated latex beads were applied to the exposed end of the tail spinal cord. After tail regeneration, HRP was applied to the new spinal cord in the regenerated tail. Examination of local spinal neurons (the primary source of axons that enter the regenerated tail spinal cord) revealed that 28% of the neurons contained both labels. This indicated that cut axons successfully regrew into the new tail spinal cord. The regenerated axons that fail to enter the new tail spinal cord can be found in the normal spinal cord immediately rostral to the regenerated tail. To determine whether these axons were making synaptic contacts, lamina IX ventral horn neurons were examined. EM photomontages of the spinal cord rostral to the regenerate tail revealed the following properties: (1) neurons rostral to regenerated tails are larger in area compare to non-regenerates (mean increase = 112%); (2) axosomatic contacts cover a greater percentage of the neuronal soma following regeneration compared to normal (mean increase = 23%); and (3) this increased innervation is the result of an increase in the number of synaptic boutons rather than larger boutons. The number of synaptic contacts in regenerated lizards returned to normal following lumbar transection, indicating that supraspinal and/or long descending propriospinal afferents were the major source of the increased synaptic contacts.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Acceleration of axonal outgrowth in motor axons from mature and old F344 rats after a conditioning lesion.

The conditioning lesion paradigm has proven to be a very useful model in which to examine the mechanisms of axonal outgrowth after injury. In the present study, we have used the conditioning lesion model to examine the ability of motor axons from mature (6-8 months) and old (22-24 months) Fischer 344 rats to form new axonal sprouts. We show that after a single lesion (sham-conditioned axons followed by a testing lesion), axonal outgrowth rates are slower at earlier vs longer postlesion times in mature rats: between 4 and 8 days postlesion, outgrowth rates are 2.4 +/- 0.4 mm/day, whereas between 8 and 11 days postlesion outgrowth rates are 4.6 +/- 0.7 mm/day. After a single lesion in the old rat, at early postlesion times, the axonal outgrowth rate is 1.9 +/- 0.4 mm/day but with increasing time after injury, outgrowth rates slow down to 1.1 +/- 0.8 mm/day. In conditioned motor axons from mature rats, outgrowth rates increase from 3.1 +/- 0.4 mm/day at early postlesion times to 5.2 +/- 0.6 mm/day at longer postlesion times. An even more dramatic increase in outgrowth rate is seen in conditioned axons from old rats: 2.4 +/- 0. 4 mm/day at early postlesion times to 6.3 +/- 1.0 mm/day at later times after lesion. There is no change in the initial delay before sprouting under any condition. These data support the hypothesis that axons from old animals can be stimulated to repair themselves at rates comparable to those seen in younger animals and suggest that there may be an absolute maximum outgrowth rate attainable by newly forming axon sprouts.

Aging↗

Fibroblast growth factor receptor function is required for the orderly projection of ganglion cell axons in the developing mammalian retina.

During the early stages of development various cell adhesion molecules (CAMs) and fibroblast growth factor receptors (FGFR) are expressed throughout the retinal neuroepithelium. The ability of retinal ganglion cells to project their axons to the optic fissure depends, in part, on cell-cell interactions mediated by cell adhesion molecules. In the present study we show that the ability of the firstborn rat retinal ganglion cells to extend axons in vitro can be stimulated by NCAM and L1, but not N-cadherin. Both CAM responses can be fully inhibited by antibodies that block neuronal fibroblast growth factor receptor function and by agents that block defined steps in the FGFR signal transduction cascade. When added to living E13.5 rat retinal whole-mount preparations the same agents induced errors in the orderly establishment of young axon patterns in the retinal periphery and caused axons in the retinal center to defasciculate. These results suggest that the activation of the fibroblast growth factor receptor signal cascade not only promotes survival and proliferation of various cell types but can also mediate intraretinal axon guidance.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

The course of regenerating retinal axons in the frog chiasma: the influence of axons from the other eye.

There is evidence, from a variety of species, that axons arising from the two eyes interact as they pass through the optic chiasma. In this paper we examine the effect of altering the composition of the normal chiasmatic environment on the course taken by regenerating axons in Xenopus. We show that the usual contralateral route of such axons in the optic chiasma is not affected by the absence of axons from the other eye. We have not observed any influence of embryonic enucleation, or eye removal before the onset of metamorphosis, on either the normal ipsilaterally projecting axons or the contralateral route taken by regenerating axons. Further, we have found no effect of the degeneration of the other projection, either for long or short periods of time, suggesting that axonal debris does not influence the course of regenerating axons. The simultaneous regeneration of the two projections also has no effect on the trajectory of regenerating axons. We conclude that in spite of the close association of axons from the two eyes in the chiasma, there is no interaction involved in Xenopus in the generation of the decussation pattern.

Animals↗

Modulation of axonal excitability mediated by surround electric activity: an intra-axonal study.

Intra-axonal recordings were obtained in vitro from frog sciatic nerve axons. Adjusting whole nerve stimulation current to just subthreshold for the impaled axon elicited triphasic threshold changes in that axon. Threshold changes were determined by direct intra-axonal current application. Graded subthreshold depolarizations were present in many axons during the passage of action potentials in surrounding axons. When nerve branches were stimulated and axon recordings were obtained from the main nerve trunk, both branches, the one that activated the impaled axon and the one that did not, elicited threshold changes in the impaled axon. These data indicate on a cellular level that impulse activity in an intact nerve bundle can modulate the excitability of adjacent nonactivated fibers.

Animals↗

The perinotochordal mesenchyme acts as a barrier to axon advance in the chick embryo: implications for a general mechanism of axonal guidance.

To test the hypothesis that the perinotochordal mesenchyme (the sclerotome ventral to the spinal nerve pathway) is a barrier to axonal advance in the chick embryo, we determined whether axons directly confronted with perinotochordal mesenchyme would turn to avoid it. The initial direction of motor axon outgrowth was altered by rotating the right half of the neural tube after deleting the left half. Perinotochordal mesenchyme was identified histologically or by peanut agglutinin (PNA) binding. We found that axons turned to avoid the perinotochordal mesenchyme and traversed only the dorsal-anterior sclerotome at all stages of outgrowth. When the ventral root was positioned at the midline, axons projected around the perinotochordal mesenchyme and formed spinal nerves on both sides of the embryo. Furthermore, neural crest cells and sensory axons did not penetrate perinotochordal mesenchyme, even in the absence of motor axons. In contrast, perinotochordal mesenchyme did not exhibit inhibitory function and did not differentially bind PNA when the notochord was deleted; axons ramified widely within it. We conclude that the dorsal-anterior sclerotome is permissive and that the perinotochordal mesenchyme is relatively inhibitory for the advance of axons and neural crest cells. Two additional pairs of tissues provide similar permissive/inhibitory contrasts in the embryo, the anterior/posterior sclerotome and the plexus/pelvic girdle mesenchyme. We hypothesize that guidance by all three pairs is mediated by the same set of cellular interactions and has a common molecular basis. We further propose that the transient expression of substances characteristic of these contrasting tissue pairs could serve to guide axons elsewhere, in both the peripheral and the central nervous systems.

Animals↗

Selective effects of DSP-4 on locus coeruleus axons: are there pharmacologically different types of noradrenergic axons in the central nervous system?

There is considerable evidence from biochemical studies that the transmitter-depleting action of drugs and neurotoxins which act upon central noradrenergic (NA) axon terminals is not uniform in different brain regions. Among NA axons, those originating in the locus coeruleus (LC) have been proposed to be most susceptible to the action of NA neurotoxins such as N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4). The studies described here were conducted to determine whether this differential susceptibility to DSP-4 reflects a pharmacological heterogeneity between different populations of NA axons. To determine whether DSP-4 acts selectively upon LC axons, we have characterized the effects of this drug on NA axons in different brain regions, by using noradrenaline and dopamine-beta-hydroxylase (D beta H) immunohistochemistry. Following systemic administration of DSP-4, there was an almost complete loss of noradrenaline and D beta H staining in brain regions innervated by LC axons. No effects of the drug treatment were detected in brain regions innervated primarily by non-coerulean NA axons. These results demonstrate that both the transmitter-depleting and the neurodegenerative action of DSP-4 are restricted to NA axons originating in the LC. To explore the basis for this selectivity, noradrenaline uptake studies were conducted using synaptosomes from brain regions in which NA axons differ in their response to DSP-4. The results reveal a significant difference in the affinity of DSP-4 for the noradrenaline uptake carrier in cortical and hypothalamic synaptosomes. This finding is compatible with the hypothesis that the noradrenaline uptake carrier is pharmacologically distinct in LC and non-coerulean NA axons. This heterogeneity in noradrenaline uptake raises the question whether other drugs may also have differential actions on LC and non-coerulean NA neurons.

Adrenergic Agents↗

Differential functions of the C. elegans FGF receptor in axon outgrowth and maintenance of axon position.

Wiring of the nervous system requires that axons navigate to their targets and maintain their correct positions in axon fascicles after termination of axon outgrowth. We show here that the C. elegans fibroblast growth factor receptor (FGFR), EGL-15, affects both processes in fundamentally distinct manners. FGF-dependent activation of the EGL-15 tyrosine kinase and subsequently the GTPase LET-60/ras is required within epidermal cells, the substratum for most outgrowing axon, for appropriate outgrowth of specific axon classes to their target area. In contrast, genetic elimination of the FGFR isoform EGL-15(5A), defined by the inclusion of an alternative extracellular interimmunoglobulin domain, has no consequence for axon outgrowth but leads to a failure to postembryonically maintain axon position within defined axon fascicles. An engineered, secreted form of EGL-15(5A) containing only its ectodomain is sufficient for maintenance of axon position, thus providing novel insights into receptor tyrosine kinase function and the process of maintaining axon position.

Animals↗

Physiological roles of axonal ankyrins in survival of premyelinated axons and localization of voltage-gated sodium channels.

440 kD ankyrin-B and 480/270 kD ankyrin-G are membrane skeletal proteins with closely related biochemical properties yet distinctive physiological roles in axons. These proteins associate with spectrin-actin networks and also bind to integral membrane proteins including the L1 CAM family of cell adhesion molecules and voltage-gated sodium channels. 440 kD ankyrin-B is expressed with L1 in premyelinated axon tracts, and is essential for survival of these axons, at least in the case of the optic nerve. 440 ankyrin-B may collaborate with L1 in transcellular structures that mediate axon fasciculation and mechanically stabilize axon bundles, although these proteins may also be involved in axon pathfinding. Ankyrin-B (-/-) mice exhibit loss of L1 from premyelinated axon tracts and a similar, although much more severe, phenotype to L1 (-/-) mice and humans with L1 mutations. Ankyrin-B and L1 thus are candidates to collaborate in the same structural pathway and defects in this pathway can lead to nervous system malformations and mental retardation. 480/270 kD ankyrin-G are highly concentrated along with the L1CAM family members neurofascin and NrCAM at nodes of Ranvier and axon initial segments. Voltage-gated sodium channels bind directly to ankyrins, and are likely to associate in a ternary complex containing neurofascin/NrCAM, and ankyrin-G. Mice with ankyrin-G expression abolished in the cerebellum exhibit loss of ability of Purkinje neurons to fire action potentials, as well as loss of restriction of neurofascin/NrCAM to axon initial segments. Ankyrin-G thus is a key component in assembly of functional components of the axon initial segment and possibly the node of Ranvier.

Animals↗

A morphological study of the axons and recurrent axon collaterals of cat alpha-motoneurones supplying different functional types of muscle unit.

1. Cat alpha-motoneurones supplying muscle units of the soleus S type and gastrocnemius S, FR and FF types were injected intracellularly with horseradish peroxidase. 2. Ten alpha-motoneurones of each motor unit type were collected for morphological analysis of the intramedullary parts of their axonal systems including the recurrent axon collaterals. 3. The alpha-motor axon diameters in the spinal cord white matter were significantly smaller for the soleus motor units (mean = 5.2 micrometer) than for the gastrocnemius S units (mean = 6.4 micrometer), which in turn differed significantly from those of the gastrocnemius FR (mean 7.4 micrometer) and FF (mean = 7.3 micrometer types. 4. The number of axon collateral outbulgings, interpreted as synaptic terminals, which originated from the soleus motor axons (mean = 27.8) was significantly smaller, white that of the gastrocnemius FF motor axons (mean = 98.1) was significantly larger, than the number of outbulgings from the gastrocnemius S (mean = 44.4) and FR (mean = 53.8) motor axons. The latter two types were not significantly different. 5. In transverse sections the axon collateral outbulgings were found not only in the classical Renshaw cell area ventromedial to the main motor nuclei but also within the homonymous motor nucleus. However, only some of the neurones projected to the latter area. Rostrocaudally, the outbulgings were distributed within a distance of less than 1 mm around the position of the parent cell bodies. 6. Some physiological implications of the observed differences between axon collateral systems of various functional types of alpha-motoneurones were discussed in relation to the present knowledge of the effects of the recurrent axon collaterals during different types of involuntary and voluntary activation of the alpha-motoneurones.

Animals↗

The extent of axonal exposure and axo-axonal apposition in the non-myelinated nerve fibres of peripheral nerve trunks and their dependence on buffer molarity.

Nineteen rats were perfused intracardially with a 2% glutaraldehyde solution in cacodylate buffers adjusted in molarity from 0 to 0 . 4 m. Ultrathin sections of the inferior alveolar nerve were photographed in the electron microscopy. From prints of unmyelinated nerve fibres, the following measurements were made: axon circumference, the proportion of axons which were incompletely covered by the Schwann cell and the extent of this 'exposure', the proportion of axons which were apparently in contact with each other and the extent of this contact and the axon-Schwann cell gap. Axonal size and the spacing between the axon and Schwann cell were not related to buffer molarity. Very few (0-3 . 4%) of the axons were in contact and the degree of contact was unrelated to buffer concentration. Of the axons, 10-34% were partially unsheathed, the proportion being linearly related to the molarity of the buffer vehicle. It is concluded that axo-axonal apposition is an insignificant feature in this nerve trunk, but that axonal exposure is a constant finding although its extent is dependent on the conditions of fixation.

Animals↗

Microtubule disorientation and axonal swelling in unmyelinated sensory axons during vincristine-induced painful neuropathy in rat.

Neuropathic pain accompanies peripheral nerve injury following a variety of insults including metabolic disorders, traumatic injury, and exposure to neurotoxins such as vincristine and taxol. Vincristine, a microtubule depolymerizing drug, produces a peripheral neuropathy in humans that is accompanied by painful paresthesias and dysesthesias (Sandler et al., [1969] Neurology 19:367-374; Holland et al. [1973] Cancer Res. 33:1258-1264). The recent development of an animal model of vincristine-induced neuropathy provides an opportunity to investigate mechanisms underlying this form of neuropathic pain. Systemic vincristine (100 microg/kg) produces hyperalgesia to mechanical stimuli during the second week of administration, which persists for more than a week (Aley et al. [1996] Neuroscience 73:259-265). To test the hypothesis that changes in microtubule structure in nociceptive sensory neurons accompany vincristine-induced hyperalgesia, we analyzed unmyelinated axons in saphenous nerves of vincristine-treated rats. This study constitutes the first quantitative ultrastructural analysis of the cytoskeleton of unmyelinated axons in peripheral nerve during neuropathic hyperalgesia. There was no evidence of unmyelinated fiber loss or a decrease in the number of microtubules per axons. There was, however, a significant decrease in microtubule density in unmyelinated axons from vincristine-treated rats. This decrease in microtubule density was due to a significant increase in the cross-sectional area of unmyelinated axons, suggesting swelling of axons. In addition, vincristine-treated axons had significantly fewer microtubules cut in cross-section and significantly more tangentially oriented microtubules per axon compared to controls. These results suggest that vincristine causes disorganization of the axonal microtubule cytoskeleton, as well as an increase in the caliber of unmyelinated sensory axons.

Animals↗