SEARCH · Search PubMed

Results for “Axons”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources

PubMed2003

Block of slow axonal transport and axonal growth by brefeldin A in compartmented cultures of rat sympathetic neurons.

Disruption of the Golgi by brefeldin A (BFA) has been reported to block fast axonal transport and axonal growth. We used compartmented cultures of rat sympathetic neurons to investigate its effects on slow axonal transport. BFA (1 micro g/ml) applied to cell bodies/proximal axons for 6-20 h disrupted the Golgi, reversibly blocked axonal growth, and reversibly blocked anterograde transport of all proteins, including tubulin. The retrograde transport of nerve growth factor (NGF) was also blocked. The phosphorylation of Erk1 and Erk2 in response to NGF was unaffected after 6 h of treatment with BFA, suggesting that the block of axonal transport was specific and direct. Consistent with its principal site of action at the Golgi, no effects were observed when BFA was applied only to the distal axons. Block of fast anterograde and retrograde axonal transport is consistent with the role of the Golgi in supplying transport vesicles. Block of slow axonal transport was surprising, and further results indicated that transport of tubulin en route along the axon was arrested by application of BFA to the cell bodies, suggesting that a continuous supply of anterograde transport vesicles from the Golgi is required to maintain slow axonal transport of cytoskeletal proteins.

Animals↗

PubMed1987

The disturbance of the fast axonal transport of protein by passive stretching of an axon in Aplysia.

1. Radioactive amino acid, either [3H]leucine or [3H]proline, was injected into neurone R2 in the abdominal ganglion of Aplysia kurodai to investigate the intra-axonal transport of protein in a single axon. 2. Some of the injected amino acid which was not utilized for protein synthesis diffused intra-axonally with a diffusion constant of 6.0 X 10(-6) cm2/s (25 degrees C), which is the value expected from the known diffusion constants of acetylcholine and gamma-aminobutyric acid in the axoplasm (Koike & Nagata, 1979). The true length of the zigzagging axon in the nerve bundle was measured by the diffusion distances. 3. The radioactive proteins newly synthesized in the cell body from either of the injected amino acid were transported axonally in a single axon of R2. 4. Elongation of the axon resulted in a suppression of the fast axonal transport of the proteins and the amount of protein transported. This contrasts with the observation that action potential propagation along the elongated axon never failed. 5. A possible site for the suppression of the axonal transport would be axonal microtubules whose structure is not likely to be resistant to the distortion caused by the elongation.

Animals↗

PubMed2002

Ultrastructural observation of effect of moderate hypothermia on axonal damage in an animal model of diffuse axonal injury.

OBJECTIVE: To investigate the effect of moderate hypothermia on responses of axonal cytoskeleton to axonal injury in the acute stage of injury. METHODS: Of fifteen adult guinea pigs, twelve animals were subjected to stretch injury to the right optic nerves and divided into the normothermic group (n = 6) in which the animal's core temperature was maintained at 36.0-37.5 degrees C and the hypothermia group (n = 6) in which the core temperature was reduced to 32.0-32.5 degrees C after stretch injury. Remaining three animals sustained no injury to the right optic nerves and served as control group. Half of injured animals (n = 3) of either normothermic group or hypothermic group were killed at either 2 hours or 4 hours after injury. The ultrastructural changes of axonal cytoskeleton of the right optic nerve fibers from the animals were examined under a transmission electron microscope and analyzed by quantitative analysis with a computer image analysis system. RESULTS: At 2 hours after stretch injury, there was a significant reduction in the mean number of microtubules (P < 0.001), and a significant increase in the mean intermicrotubule spacing (P < 0.05 or P < 0.01) in axons of all sizes in normothermic animals. The mean number of neurofilaments also decreased statistically (P < 0.01) in large and medium subgroups of axons in the same experimental group at 2 hours. By 4 hours, the large subgroup of axons in normothermic animals still demonstrated a significant decline in the mean number of microtubules (P < 0.01) and an increase in the mean intermicrotubule spacing (P < 0.05), while the medium and small subgroups of axons displayed a significant increase in the mean number of neurofilaments (P < 0.05) and reduction in the mean interneurofilament spacing (P < 0.05). On the contrary, either the mean number of microtubules and the mean intermicrotubule spacing, or the mean number of neurofilaments and interneurofilament spacing in axons of all sizes in hypothermic stretch-injured animals was not significant different from the mean values of sham-operated animals. CONCLUSIONS: Posttraumatic moderate hypothermia induced immediately after axonal injury results in substantial protection of axonal cytoskeleton and ameliorates axonal damage.

Animals↗

PubMed1996

Antibody that neutralizes myelin-associated inhibitors of axon growth does not interfere with recognition of target-specific guidance information by rat retinal axons.

During development, many CNS projection neurons establish topographically ordered maps in their target regions. Myelin-associated inhibitors of neurite growth contribute to the confinement of fiber tracts during development and limit plastic changes after CNS projections have been formed. Neutralization of myelin-associated growth inhibitors leads to an expansion of the retinal innervation of the superior colliculus (SC). In the lesioned adult mammalian CNS, these long projection neurons are usually unable to regrow axons over long distances after lesion due to myelin-associated inhibitors, which interfere with axonal growth in vivo and in vitro. Application of a specific antibody directed against myelin-inhibitors (IN-1) promotes regrowth of corticospinal tract or retinal ganglion cell axons. In the present study, we asked whether application of an antibody to myelin-associated growth inhibitors would lead to disturbances of target-specific axon guidance. To examine this issue, we used an in vitro model, the "stripe assay", to examine the behavior of rat retinal ganglion cell axons on membranes from embryonic and deafferented adult rat SC. On membrane preparations from embryonic rat SC, retinal fibers avoid posterior tectal membranes, possibly due to the presence of a repulsive factor. Nasal retinal axons show a random growth pattern. On membranes prepared from the deafferented adult rat SC, temporal and nasal axons prefer to grow on membranes prepared from their specific target region, which suggests the involvement of target-derived attractive guidance components. The results of the present study show that retinal axons grow significantly faster in the presence of IN-1 antibody that neutralizes myelin-associated growth inhibitors present in the membrane preparations from the adult rat SC. IN-1 antibody, however, does not interfere with specific axonal guidance. This suggests that axonal guidance and specific target finding are independently regulated in retinal axons.

Afferent Pathways↗

PubMed2004

Computational modeling of retinotopic map development to define contributions of EphA-ephrinA gradients, axon-axon interactions, and patterned activity.

The topographic projection of retinal ganglion cell (RGC) axons to mouse superior colliculus (SC) or chick optic tectum (OT) is formed in three phases: RGC axons overshoot their termination zone (TZ); they exhibit interstitial branching along the axon that is topographically biased for the correct location of their future TZ; and branches arborize preferentially at the TZ and the initial exuberant projection refines through axon and branch elimination to generate a precise retinotopic map. We present a computational model of map development that demonstrates that the countergradients of EphAs and ephrinAs in retina and the OT/SC and bidirectional repellent signaling between RGC axons and OT/SC cells are sufficient to direct an initial topographic bias in RGC axon branching. Our model also suggests that a proposed repellent action of EphAs/ephrinAs present on RGC branches and arbors added to that of EphAs/ephrinAs expressed by OT/SC cells is required to progressively restrict branching and arborization to topographically correct locations and eliminate axon overshoot. Simulations show that this molecular framework alone can develop considerable topographic order and refinement, including axon elimination, a feature not programmed into the model. Generating a refined map with a condensed TZ as in vivo requires an additional parameter that enhances branch formation along an RGC axon near sites that it has a higher branch density, and resembles an assumed role for patterned neural activity. The same computational model generates the phenotypes reported in ephrinA deficient mice and Isl2-EphA3 knockin mice. This modeling suggests that gradients of counter-repellents can establish a substantial degree of topographic order in the OT/SC, and that repellents present on RGC axon branches and arbors make a substantial contribution to map refinement. However, competitive interactions between RGC axons that enhance the probability of continued local branching are required to generate precise retinotopy.

Animals↗

PubMed2001

Are pioneer axons guided by regulatory gene expression domains in the zebrafish forebrain? High-resolution analysis of the patterning of the zebrafish brain during axon tract formation.

Although the principles of axon growth are well understood in vitro the mechanisms guiding axons in vivo are less clear. It has been postulated that growing axons in the vertebrate brain follow borders of neuroepithelial cells expressing specific regulatory genes. In the present study we reexamined this hypothesis by analysing the earliest growing axons in the forebrain of embryonic zebrafish. Confocal laser scanning microscopy was used to determine the spatiotemporal relationship between growing axons and the expression pattern of eight regulatory genes in zebrafish brain. Pioneer axons project either longitudinally or dorsoventrally to establish a scaffold of axon tracts during this developmental period. Each of the regulatory genes was expressed in stereotypical domains and the borders of some were oriented along dorsoventral and longitudinal planes. However, none of these borders clearly defined the trajectories of pioneer axons. In two cases axons coursed in proximity to the borders of shh and pax6, but only for a relatively short portion of their pathway. Only later growing axons were closely apposed to the borders of some gene expression domains. These results suggest that pioneer axons in the embryonic forebrain do not follow continuous pathways defined by the borders of regulatory gene expression domains.

Animals↗

PubMed2005

Death of an axon: studying axon loss in development and disease.

The loss of axon branches is a common feature of both the developing and the diseased nervous system. Despite its fundamental importance, a clear mechanistic understanding is lacking on how axonal loss occurs. However, the first molecular inroads into post-traumatic (Wallerian) axon degeneration have recently been made. In parallel, imaging techniques that allow visualizing single axons in vivo are providing a first glimpse at the cellular mechanisms of active dismantling of superfluous or diseased axons. This gives hope that soon a clearer mechanistic understanding of axon loss will emerge: comparing different forms of axon loss will reveal the spectrum of axon loss mechanisms; studies aimed at integrating the known molecular and cellular players during axon loss will provide mechanistic insight into axon dismantling; finally-by understanding how axons are normally lost-we will hopefully find ways to protect them during neurological disease or after trauma.

Animals↗

PubMed1995

Backpropagation of action potentials generated at ectopic axonal loci: hypothesis that axon terminals integrate local environmental signals.

This review deals with the fascinating complexity of presynaptic axon terminals that are characterized by a high degree of functional distinctiveness. In vertebrate and invertebrate neurons, all-or-none APs can take off not only from the axon hillock, but also from ectopic axonal loci including terminals. Invertebrate neurons display EAPs, for instance alternating with somatic APs, during survival functions. In vertebrate, EAPs have been recorded in the peripheral and central nervous systems in time relationship with physiological or pathological neuronal activities. In motor or sensory axon, EAP generation may be the cause of motor dysfunctioning or sensory perceptions and pain respectively. Locomotion is associated with rhythmic depolarizations of the presynaptic axonal membrane of primary afferents, which are ridden by robust EAP bursts. In central axons lying within an epileptic tissue EAP discharges, coinciding with paroxysmal ECoG waves, get longer as somatic discharges get shorter during seizure progression. Once invaded by an orthodromic burst, an ectopic axonal locus can display an EAP after discharge. Such loci can also fire during hyperpolarization or the postinhibitory excitatory period of the parent somata, but not during their tonic excitation. Neurons are thus endowed with electrophysiological intrinsic properties making possible the alternate discharges of somatic APs and EAPs. In invertebrate and vertebrate neurons, ectopic axonal loci fire while the parent somata stop firing, further suggesting that axon terminal networks are unique and individual functional entities. The functional importance of EAPs in the nervous systems is, however, not yet well understood. Ectopically generated axonal APs propagate backwards and forwards along the axon, thus acting as a retrograde and anterograde signal. In invertebrate neurons, somatically and ectopically generated APs cannot have the same effect on the postsynaptic membrane. As suggested by studies related to the dorsal root reflex, EAPs may not only be implied in the presynaptic modulation of transmitter release but also contribute significantly during their backpropagation to a powerful control (collision process) of incoming volleys. From experimental data related to epileptiform activities it is proposed that EAPs, once orthodromically conducted, might potentiate synapses, initiate, spread or maintain epileptic cellular processes. For instance, paroxysmal discharges of EAPs would exert, like a booster-driver, a powerful synchronizing synaptic drive upon a large number of excitatory and inhibitory postsynaptic neurons. We have proposed that, once backpropagated, EAPs are likewise capable of initiating (and anticipating) threshold and low-threshold somatodendritic depolarizations. Interestingly, an antidromic EAP can modulate the excitability of the parent soma.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1994

5-hydroxydopamine-labeled dopaminergic axons: three-dimensional reconstructions of axons, synapses and postsynaptic targets in rat neostriatum.

Previous studies employing 5-hydroxydopamine to identify nigrostriatal dopaminergic axons and their synapses found that labeled axons made few synapses or that asymmetric contacts predominated. In contrast, recent studies using tyrosine hydroxylase or dopamine antibody techniques indicate that presumed dopaminergic axons form small symmetric contacts. We re-examined 5-hydroxydopamine-labeled material from the rat neostriatum using serial three-dimensional reconstruction techniques to characterize the morphology of labeled axons, synapses and postsynaptic targets. This ultrastructural analysis revealed a class of heavily labeled axons that are small (0.06-1.5 microns in diameter) and lack large varicosities. These axons form small (0.011-0.09 microns 2), en passant, symmetric synapses, mainly onto dendritic spines and spiny dendritic shafts and, in some cases, onto aspiny dendritic segments near branch points. The sites of these synapses along the axon appeared unrelated to the locations of axonal enlargements, suggesting that counting varicosities may not be an accurate indication of the extent of dopaminergic innervation in the neostriatum. The characteristics of these 5-hydroxydopamine-labeled elements correspond in all respects to axons and synapses identified as dopaminergic by immunohistochemistry in previous studies. In tissue in which all labeled and unlabeled synapses were classified, approximately 9% of all synapses were identified as dopaminergic by this type of label. Three-dimensional reconstructions provided additional insight concerning the interaction of dopaminergic afferents with postsynaptic striatal targets and their relation to other afferents to these neurons. They reveal that a short, unbranched dopaminergic axonal segment can make multiple synapses onto dendritic spines, shafts and branch points of one or more dendrites. In addition, one dendrite can receive contacts from several labeled axons. Dopamine synapses onto spines are always associated with unlabeled, asymmetric synapses onto the same spine. Synapses of various morphologies with a distinctly different, lighter form of labeling were much rarer, and may represent other aminergic afferents to the neostriatum. The presence of this second form of label in earlier 5-hydroxydopamine studies may have contributed to the long-standing controversy over the appearance of dopaminergic synapses examined by different techniques. Our results help to resolve this controversy and confirm that the nigrostriatal projection makes small symmetric synapses with a variety of striatal targets.

Animals↗

PubMed2007

Temporal target restriction of olfactory receptor neurons by Semaphorin-1a/PlexinA-mediated axon-axon interactions.

Axon-axon interactions have been implicated in neural circuit assembly, but the underlying mechanisms are poorly understood. Here, we show that in the Drosophila antennal lobe, early-arriving axons of olfactory receptor neurons (ORNs) from the antenna are required for the proper targeting of late-arriving ORN axons from the maxillary palp (MP). Semaphorin-1a is required for targeting of all MP but only half of the antennal ORN classes examined. Sema-1a acts nonautonomously to control ORN axon-axon interactions, in contrast to its cell-autonomous function in olfactory projection neurons. Phenotypic and genetic interaction analyses implicate PlexinA as the Sema-1a receptor in ORN targeting. Sema-1a on antennal ORN axons is required for correct targeting of MP axons within the antennal lobe, while interactions amongst MP axons facilitate their entry into the antennal lobe. We propose that Sema-1a/PlexinA-mediated repulsion provides a mechanism by which early-arriving ORN axons constrain the target choices of late-arriving axons.

Animals↗

PubMed1997

Axonal cytoskeletal changes after non-disruptive axonal injury.

In animal models of human diffuse axonal injury, axonal swellings leading to secondary axotomy occur between 2 and 6 h after injury. But, analysis of cytoskeletal changes associated with secondary axotomy has not been undertaken. We have carried out a quantitative analysis of cytoskeletal changes in a model of diffuse axonal injury 4 h after stretch-injury to adult guinea-pig optic nerves. The major site of axonal damage was the middle portion of the nerve. There was a statistically significant increase in the proportion of small axons with a diameter of 0.5 micron and smaller in which there was compaction of neurofilaments. Axons with a diameter greater than 2.0 microns demonstrated an increased spacing between cytoskeletal elements throughout the length of the nerve. However, in the middle segment of the nerve these larger axons demonstrated two different types of response. Either, where periaxonal spaces occurred, there was a reduction in axonal calibre, compaction of neurofilaments but no change in their number, and a loss of microtubules. Or, where intramyelinic spaces occurred there was an increased spacing between neurofilaments and microtubules with a significant loss in the number of both. Longitudinal sections showed foci of compaction of neurofilaments interspersed between regions where axonal structure was apparently normal. Neurofilament compaction was correlated with disruption of the axolemma at these foci present some hours after injury. We suggest that the time course of these axonal cytoskeletal changes after stretch-injury to central axons is shorter than those changes documented to occur during Wallerian degeneration.

Animals↗

PubMed1985

Microtubule-associated protein 2 within axons of spinal motor neurons: associations with microtubules and neurofilaments in normal and beta,beta'-iminodipropionitrile-treated axons.

We have examined the distribution of microtubule-associated protein 2 (MAP2) in the lumbar segment of spinal cord, ventral and dorsal roots, and dorsal root ganglia of control and beta,beta'-iminodipropionitrile-treated rats. The peroxidase-antiperoxidase technique was used for light and electron microscopic immunohistochemical studies with two monoclonal antibodies directed against different epitopes of Chinese hamster brain MAP2, designated AP9 and AP13. MAP2 immunoreactivity was present in axons of spinal motor neurons, but was not detected in axons of white matter tracts of spinal cord and in the majority of axons of the dorsal root. A gradient of staining intensity among dendrites, cell bodies, and axons of spinal motor neurons was present, with dendrites staining most intensely and axons the least. While dendrites and cell bodies of all neurons in the spinal cord were intensely positive, neurons of the dorsal root ganglia were variably stained. The axons of labeled dorsal root ganglion cells were intensely labeled up to their bifurcation; beyond this point, while only occasional central processes in dorsal roots were weakly stained, the majority of peripheral processes in spinal nerves were positive. beta,beta'-Iminodipropionitrile produced segregation of microtubules and membranous organelles from neurofilaments in the peripheral nervous system portion and accumulation of neurofilaments in the central nervous system portion of spinal motor axons. While both anti-MAP2 hybridoma antibodies co-localized with microtubules in the central nervous system portion, only one co-localized with microtubules in the peripheral nervous system portion of spinal motor axons, while the other antibody co-localized with neurofilaments and did not stain the central region of the axon which contained microtubules. These findings suggest that (a) MAP2 is present in axons of spinal motor neurons, albeit in a lower concentration or in a different form than is present in dendrites, and (b) the MAP2 in axons interacts with both microtubules and neurofilaments.

Animals↗

PubMed1998

Neurofilament-dependent radial growth of motor axons and axonal organization of neurofilaments does not require the neurofilament heavy subunit (NF-H) or its phosphorylation.

Neurofilaments are essential for establishment and maintenance of axonal diameter of large myelinated axons, a property that determines the velocity of electrical signal conduction. One prominent model for how neurofilaments specify axonal growth is that the 660-amino acid, heavily phosphorylated tail domain of neurofilament heavy subunit (NF-H) is responsible for neurofilament-dependent structuring of axoplasm through intra-axonal crossbridging between adjacent neurofilaments or to other axonal structures. To test such a role, homologous recombination was used to generate NF-H-null mice. In peripheral motor and sensory axons, absence of NF-H does not significantly affect the number of neurofilaments or axonal elongation or targeting, but it does affect the efficiency of survival of motor and sensory axons. Loss of NF-H caused only a slight reduction in nearest neighbor spacing of neurofilaments and did not affect neurofilament distribution in either large- or small-diameter motor axons. Since postnatal growth of motor axon caliber continues largely unabated in the absence of NF-H, neither interactions mediated by NF-H nor the extensive phosphorylation of it within myelinated axonal segments are essential features of this growth.

Actin Cytoskeleton↗

PubMed1978

Axonal adaptations to osmotic and ionic stress in an invertebrate osmoconformer (Mercierella enigmatica Fauvel). I. Ultrastructural and electrophysiological observations on axonal accessibility.

The giant axons in Mercierella are overlaid by narrow glial processes which provide an incomplete covering of the axonal surface. Where more complete covering occurs the intercellular clefts are not sealed by tight junctional complexes. Ionic lanthanum penetrates to the surfaces of axons from sea-water-adapted animals (in normal saline and during initial exposure to hyposmotic saline) and, also, to the surface of hyposmotically adapted axons. A relatively free intercellular access to the axon surfaces is also indicated by the rapid electrical responses of sea-water-adapted axons to hyposmotic dilution and of hyposmotically adapted axons to sodium-deficient saline. The giant axon possesses an unusual ultrastructural specialization: hemidesmosome-like structures (associated with the axon membrane) which are connected to a network of neurofilaments within the axon. Theoretical considerations suggest that these structures could enable the axons to withstand appreciable excesses in intracellular hydrostatic pressure resulting from osmotic imbalance during hyposmotic stress.

Action Potentials↗

PubMed1999

Abnormal Schwann cell-axon interactions in CMT neuropathies. The effects of mutant Schwann cells on the axonal cytoskeleton and regeneration-associated myelination.

Preferential distal axonal loss is a common feature of Charcot-Marie-Tooth (CMT) hereditary neuropathies. The general hypothesis tested here is that the axonal loss in these disorders is due to perturbed Schwann cell-axon interactions resulting from primary Schwann genetic defects. The nerve xenograft model was used to study the local influence of mutant Schwann cells derived from patients on axonal properties and the regeneration-associated myelination process. Sural nerve segments from individuals with PMP22 duplications or deletions and point mutations, as well as Cx32 point mutations were grafted into cut ends of the sciatic nerve of nude mice and studied at different time intervals after grafting. CMT1A and CMTX xenografts examined at 16 weeks show that the nude mouse axons within the proximal part of grafts demonstrate a significant increase in axonal area with an increase in the neurofilament and membranous organelle density compared to distal graft and distal host segments. A preferential distal axonal loss associated with a perpetual axonal atrophy, degeneration, and axonal sprouting was observed over time with increasing frequency at 8 to 16 weeks. A distal summation of the pathology, as evidenced by a greater amount of fiber loss in the distal graft segments, was present similar to that observed in patients. These alterations were seen to a lesser extent in PMP22 deletion or point mutation xenografts and were not observed in controls. Collectively, these findings show that Schwann cells bearing the PMP22 or Cx32 genetic defects cause major perturbations in Schwann cell-axon interactions emphasizing the role of axonal component in the pathogenesis of hereditary neuropathies.

Animals↗

PubMed2000

The "waiting period" of sensory and motor axons in early chick hindlimb: its role in axon pathfinding and neuronal maturation.

During embryonic development motor axons in the chick hindlimb grow out slightly before sensory axons and wait in the plexus region at the base of the limb for approximately 24 hr before invading the limb itself (Tosney and Landmesser, 1985a). We have investigated the role of this waiting period by asking, Is the arrest of growth cones in the plexus region a general property of both sensory and motor axons? Why do axons wait? Does eliminating the waiting period affect the further development of motor and sensory neurons? Here we show that sensory axons, like motor axons, pause in the plexus region and that neither sensory nor motor axons require cues from the other population to wait in or exit from the plexus region. By transplanting older or younger donor limbs to host embryos, we show that host axons innervate donor limbs on a schedule consistent with the age of the grafted limbs. Thus, axons wait in the plexus region for maturational changes to occur in the limb rather than in the neurons themselves. Both sensory and motor axons innervate their appropriate peripheral targets when the waiting period is eliminated by grafting older donor limbs. Therefore, axons do not require a prolonged period in the plexus region to sort out and project appropriately. Eliminating the waiting period does, however, accelerate the onset of naturally occurring cell death, but it does not enhance the development of central projections or the biochemical maturation of sensory neurons.

Animals↗

PubMed1990

Altered slow axonal transport and regeneration in a myelin-deficient mutant mouse: the trembler as an in vivo model for Schwann cell-axon interactions.

The thickness of the myelin sheath in normal myelinated nerve is proportional to the diameter of the axon. In the demyelinating mutant mouse, Trembler, not only is the thickness of the myelin sheath reduced, but the caliber of associated axons is smaller. This correlation suggests that the interaction between axons and Schwann cells may affect the shape and function of axons as well as properties of myelin. Since axonal diameter depends in part on the cytoskeleton and its movement with slow axonal transport, we have compared the properties of slow transport in the sciatic nerve of control and Trembler mice. Studies of the sciatic nerve of normal mice showed that the rates for proteins moving in slow component a (SCa) and slow component b (SCb) are similar to those previously measured in rat. In Trembler mice, tubulin was transported significantly faster than in control mice, with a rate of 1.73 mm/d for Trembler compared to 1.56 mm/d in the control. In contrast, the rate for neurofilament proteins was significantly slower in the Trembler (1.15 mm/d compared to 1.38 mm/d in the control). The majority of proteins in SCb were also transported slower in Trembler than control: actin and calmodulin were transported at 2.29 mm/d as compared to 2.73 mm/d in control, while spectrin and clathrin were transported at 2.01 and 2.43 mm/d, respectively, as compared to 2.54 mm/d in control. The importance of slow axonal transport in regeneration has been suggested by the clear correlation between the rates of regeneration and the rates of SCb. Therefore, we evaluated regeneration of motor axons in Trembler mice to determine whether the regenerative response was affected by deficient Schwann cells. A slower regeneration rate was found in the Trembler (1.7 mm/d) motor axon when compared to the control (2.29 mm/d), but elongation of fibers in regeneration began after a shorter delay in the Trembler (1.6 d) than in control (2.5 d). Thus, deficient Schwann cells and poor myelination appear to affect both quantitative and qualitative properties of slow axonal transport. These changes lead to alterations in the morphological and physiological properties of affected axons.

Animals↗

PubMed1986

Elevated synthesis of an axonally transported protein correlates with axon outgrowth in normal and injured pyramidal tracts.

Axons of the adult mammalian CNS typically fail to regenerate after injury. Among the hypotheses to account for this failure is the proposition that certain axonal proteins necessary for axon growth are expressed in much greater abundance in developing than in mature neurons, and that these proteins are not reinduced after injury to mature axons (Skene and Willard, 1981b). In the present experiments, we have found that hamster pyramidal tract neurons synthesize an acidic, 43K protein that is transported into growing axons during the first 2 weeks of postnatal development, and then declines at least an order of magnitude by the fourth postnatal week. The decline in synthesis of the 43K protein coincides with the cessation of pyramidal tract axon elongation. This protein resembles a "growth-associated protein," GAP-43, which is induced during regeneration of CNS axons in lower vertebrates. The 43K protein in hamster pyramidal tract neurons is not reinduced after axotomy in adult animals, which correlates with the failure of the injured axons to regenerate. Injury to neonatal pyramidal tract axons does not reverse or delay the decline in 43K protein synthesis. This is consistent with previous findings (Kalil and Reh, 1982) that pyramidal tract axons regrow for only a brief period after neonatal injury. Taken together, these results lend support to the hypothesis that synthesis of GAP-43 is important for axon growth in development and regeneration.

Animals↗