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At least 1,621 records · Page 90Linked to original sources
PubMed1998

Myelin-associated glycoprotein is a myelin signal that modulates the caliber of myelinated axons.

Myelination increases neuronal conduction velocity through its insulating properties and an unidentified extrinsic effect that increases axonal caliber. Although it is well established that demyelination can cause axonal atrophy, the myelin molecule that regulates axonal caliber is not known. Loss of the structural proteins of compact peripheral nervous system (PNS) myelin, P0 protein, and myelin basic protein does not lead to axonal atrophy. This study demonstrates that mice with a null mutation of the myelin-associated glycoprotein (MAG) gene have a chronic atrophy of myelinated PNS axons that results in paranodal myelin tomaculi and axonal degeneration. Absence of MAG was correlated with reduced axonal calibers, decreased neurofilament spacing, and reduced neurofilament phosphorylation. Because axonal atrophy and degeneration in MAG-deficient mice occur in the absence of inflammation, hypomyelination, significant demyelination-remyelination, or gain of function mutations, these data support a functional role for MAG in modulating the maturation and viability of myelinated axons.

Animals↗
PubMed1998

Long-distance axonal regeneration in the transected adult rat spinal cord is promoted by olfactory ensheathing glia transplants.

The lack of axonal regeneration in the injured adult mammalian spinal cord leads to permanent functional impairment. To induce axonal regeneration in the transected adult rat spinal cord, we have used the axonal growth-promoting properties of adult olfactory bulb ensheathing glia (EG). Schwann cell (SC)-filled guidance channels were grafted to bridge both cord stumps, and suspensions of pure (98%) Hoechst-labeled EG were stereotaxically injected into the midline of both stumps, 1 mm from the edges of the channel. In EG-transplanted animals, numerous neurofilament-, GAP-43-, anti-calcitonin gene-related peptide (CGRP)-, and serotonin-immunoreactive fibers traversed the glial scars formed at both cord-graft interfaces. Supraspinal serotonergic axons crossed the transection gap through connective tissue bridges formed on the exterior of the channels, avoiding the channel interior. Strikingly, after crossing the distal glial scar, these fibers elongated in white and periaqueductal gray matter, reaching the farthest distance analyzed (1.5 cm). Tracer-labeled axons present in SC grafts were found to extend across the distal interface and up to 800 microm beyond in the distal cord. Long-distance regeneration (at least 2.5 cm) of injured ascending propriospinal axons was observed in the rostral spinal cord. Transplanted EG migrated longitudinally and laterally from the injection sites, reaching the farthest distance analyzed (1.5 cm). They moved through white matter tracts, gray matter, and glial scars, overcoming the inhibitory nature of the CNS environment, and invaded SC and connective tissue bridges and the dorsal and ventral roots adjacent to the transection site. Transplanted EG and regenerating axons were found in the same locations. Because EG seem to provide injured spinal axons with appropriate factors for long-distance elongation, these cells offer new possibilities for treatment of CNS conditions that require axonal regeneration.

Age Factors↗
PubMed1998

Localized sources of neurotrophins initiate axon collateral sprouting.

The sprouting of axon collateral branches is important in the establishment and refinement of neuronal connections during both development and regeneration. Collateral branches are initiated by the appearance of localized filopodial activity along quiescent axonal shafts. We report here that sensory neuron axonal shafts rapidly sprout filopodia at sites of contact with nerve growth factor-coated polystyrene beads. Some sprouts can extend up to at least 60 micro(m) through multiple bead contacts. Axonal filopodial sprouts often contained microtubules and exhibited a debundling of axonal microtubules at the site of bead-axon contact. Cytochalasin treatment abolished the filopodial sprouting, but not the accumulation of actin filaments at sites of bead-axon contact. The axonal sprouting response is mediated by the trkA receptor and likely acts through a phosphoinositide-3 kinase-dependent pathway, in a manner independent of intracellular Ca2+ fluctuations. These findings implicate neurotrophins as local cues that directly stimulate the formation of collateral axon branches.

Actins↗
PubMed2007

Localization of motoneurons that extend axons through the ventral rami of cervical nerves to innervate the trapezius muscle: a study using fluorescent dyes and 3D reconstruction method.

It has been suggested that in addition to motor axons, which extend directly into the spinal accessory nerve (SAN), ventral rami-associated motor fibers of cervical nerves also innervate the trapezius muscle. Using fluorescent dye labeling and 3D reconstruction in adult rats, this study clarifies the localization of motoneurons, which extend axons either directly through the SAN or through the ventral rami of cervical nerves to innervate the trapezius. DiI or DiI and DiO were used to label the ventral rami of cervical nerves entering the SAN, as well as branches of the SAN. We show that motoneurons whose axons pass through the ventral rami of cervical nerves and then enter the SAN, and those extending axons directly through the SAN are distributed within the same area. The neurons that extend axons through the SAN had a greater diameter than those axons that pass through the cervical nerves en route to the trapezius muscle. In addition, the axons that ultimately extend through the SAN exit the spinal cord dorsolaterally, while those that pass through the cervical nerves extend out the spinal cord through the ventral roots. We presume that the neurons that extend axons through the SAN are mainly alpha-motoneurons and that those projecting axons through the cervical nerves to the trapezius are mainly gamma-motoneurons. Taken together, these results could explain why patients in whom the SAN was used to treat brachial plexus injury retain some control of the trapezius muscle.

Animals↗
PubMed2005

Patterns of axonal branching of neurons of the substantia nigra pars reticulata and pars lateralis in the rat.

Axons from neurons of the rat substantia nigra pars reticulata (SNr) and pars lateralis (SNl) were traced after injecting their cell body with biotinylated dextran amine. Thirty-two single axons were reconstructed from serial sagittal sections with a camera lucida, whereas four other SNr axons were reconstructed in the coronal plane to determine whether they innervate the contralateral hemisphere. Four distinct types of SNr projection neurons were identified based on their main axonal targets: type I neurons that project to the thalamus; type II neurons that target the thalamus, the superior colliculus (SC), and the pedunculopontine tegmental nucleus (PPTg); type III neurons that project to the periaqueductal gray matter and the thalamus; and type IV neurons that target the deep mesencephalic nucleus (DpMe) and the SC. The axons of the SNl showed the same branching patterns as SNr axons of types I, II, and IV. The coronal reconstructions demonstrated that SNr neurons innervate the thalamus, the SC, and the DpMe bilaterally. At the thalamic level, SNr and SNl axons targeted preferentially the ventral medial, ventral lateral, paracentral, parafascicular, and mediodorsal nuclei. Axons reaching the SC arborized selectively within the deep layers of this structure. Our results reveal that the SNr and SNl harbor several subtypes of projection neurons endowed with a highly patterned set of axon collaterals. This organization allows single neurons of these output structures of the basal ganglia to exert a multifaceted influence on a wide variety of diencephalic and midbrain structures.

Animals↗
PubMed1981

Organization of spinothalamic tract axons within the rat spinal cord.

Two techniques have been used to examine the organization of spinothalamic tract axons within the spinal cord of the rat. In the initial experiments, the thalamus was filled on one side with horseradish peroxidase (HRP) using a series of small injections. The injections were preceded by lesions of various areas of the ventral quadrant. These studies indicated that the cells of origin of STT axons ascending within the ventral funiculus (VF) are located primarily in the ventral-most areas of the dorsal horn and the intermediate gray zone. The cells of origin of STT axons projecting within the ventrolateral funiculus (VLF) are located not only deep within the gray matter but in addition within the dorsal-most two thirds of the dorsal horn, the area of the spinal cord gray matter shown in previous studies to contain the vast majority of cells with cutaneous tactile and nociceptive input. To examine these projections directly, rats received either a series of HRP injections that filled the thalamus on one side or a small injection into either medial or lateral thalamus. Examination of the labeled axons in horizontal sections through the cervical cord indicated that STT axons ascending to lateral thalamus do so in the VLF. In contrast, axons terminating in medial thalamus ascend in the VF. Additional experiments have shown that axons ascending to the lateral thalamus are distributed throughout the VLF at lumbar levels. Within the thoracic cord, lateral projecting SST axons are distributed throughout much of the VLF but are not found in close proximity to the ventral horn. At cervical levels all lateral-projecting STT axons have assumed a position on the lateral rim of the VLF. These and previously published data have demonstrated that the rat spinothalamic tract is composed of two components that differ in the distribution of their cells of origin, the area of the cord in which they ascend, and the thalamic nuclei in which they terminate.

Animals↗
PubMed1981

Substrate pathways demonstrated by transplanted Mauthner axons.

A substrate pathway is a set of aligned guidance cues. (Such cues may be either cells or molecules.) CNS substrate pathways can be demonstrated by transplanting axons to different starting locations. The stereotyped routes of transplanted axons will then demonstrate the locations of effective substrate pathways. To map CNS substrate pathways, Mauthner axons were transplanted to various unnatural locations along the CNS of Xenopus embryos. The routes of 24 experimental Mauthner axons were traced. Twenty-one of these axons grew along parts of a stereotyped route extending in the ventral marginal zone from the caudal diencephalon through the spinal cord. This ventral substrate pathway ran the length of the basal plate; thus, we call it a basal substrate pathway. One experimental Mauthner axon grew along the alar substrate pathway previously demonstrated by transplanted optic axons. The demonstrations of the alar and the basal substrate pathways suggest that during development a few long substrate pathways organize the overall layout of the long tracts of the CNS. We propose that the pattern of the earliest CNS substrate pathways is established in the neural plate and is topologically preserved as the neural plate rolls into a neural tube. This pattern may be manifest as the three-dimensional organization of the early marginal zones formed by the peripheral processes (the endfeet) of certain developing ependyma and radial glia. Subsequently, the detailed anatomy of the axon tracts and the specific terminations of individual axons are probably determined by other local chemical cues.

Brain↗
PubMed1985

Regeneration of lumbar dorsal root axons into the spinal cord of adult frogs (Rana pipiens), an HRP study.

Lumbar dorsal roots of adult frogs were crushed or cut and reanastomosed. Following survival times of up to 75 days, the regenerating dorsal roots were recut and anterogradely injury-filled with horseradish peroxidase. This revealed that in the adult frog, regenerating axons re-enter the spinal cord. Comparison of the distribution of these axons with that of normal dorsal root axons showed that there is a partial restoration of the segmental distribution in the gray matter. However, the long ascending sensory tract of the dorsal funiculus was not restored. The dorsal funiculus was markedly gliotic and had relatively few labelled, regenerated axons. The labelled axons that were seen in the dorsal funiculus either extended longitudinally for a distance just beneath the pia, apparently in association with the glia limitans, or traversed the region to enter the dorsal gray matter. Most of the large and small diameter axons that entered the gray matter did so by passing through the region of the dorsolateral fasciculus. Within the gray matter, small diameter, regenerated axons arborized in the region of the dorsal terminal field, a region that has been shown in the normal frog to receive cutaneous afferents only. Many large diameter axons, presumably muscle afferents, arborized in the ventral terminal field, a region shown in the normal frog to receive muscle afferents exclusively. However, many of these large diameter axons had arborizations that extended to both terminal fields, thus suggesting that some abberant connections are made during dorsal root regeneration in the adult frog.

Animals↗
PubMed1987

Distribution of laminin and fibronectin along peripheral trigeminal axon pathways in the developing chick.

The trigeminal region of the chick was studied with indirect immunofluorescence in order to determine whether extracellular matrix components might be distributed in such a way as to guide trigeminal axons to their peripheral targets in the mandibular arch. Tissue sections from stages 13-15 and 21/22 were immunolabeled indirectly with affinity-purified antibodies raised against fibronectin and laminin, two extracellular matrix glycoproteins that support axon growth in vitro. Fibronectin was distributed ubiquitously throughout the head mesenchyme prior to and during initial axon growth from the brainstem (stages 13-15). Shortly after trigeminal axons reached their target tissues (stage 21/22), fibronectin immunolabeling was distributed throughout the head mesenchyme, but was present only at low levels in the trigeminal ganglion and motor nerve. Laminin immunolabeling was distributed in the lateral head mesenchyme at stage 13 as small specks and patches. At stage 14, when the motor axons first exit from the brainstem, short, linear arrays of laminin immunostaining were present from the basement membrane of the neural tube to the core of the mandibular arch, and many were parallel to the direction of axon growth. By stage 21/22 the trigeminal ganglion and motor root showed intense antilaminin immunofluorescence as did the central core of the mandibular arch. These studies suggest that the distribution of fibronectin within the head mesenchyme cannot give directional information to the growing trigeminal axons because of its homogeneous distribution. However, the initial distribution of laminin during the earliest stages of axon outgrowth may provide an extracellular matrix pathway that permits trigeminal axons to reach their targets.

Animals↗
PubMed1989

Light microscopic study of degenerating cobalt-filled optic axons in goldfish: role of microglia and radial glia in debris removal.

Labeling severed axons with cobaltous-lysine ultimately leads to the degeneration of their distal segments. The present study was designed to determine whether microglia and radial glia have comparable roles in the elimination of degenerating axons. Another purpose was to determine whether the cobalt could escape from degenerating axons and enter intact neuronal cells. Optic axons were filled with cobaltous-lysine for 1 day and the retinal projections were examined from 1 to 106 days later. Optimal filling was obtained 1 day postlabeling. The number of filled axons in the optic tract was significantly reduced at the 2-day time point, indicating that many axons had disintegrated. Many axons contained large swellings that resembled cells. However, transneuronally labeled neuronal cells were never observed. Labeled, rounded microglia appeared among the degenerating axons at the 3-day time point, and the microglia changed shape at 5 days. They became elongated and manifested many processes. In addition, the microglia began to move toward, and entered, the ventricles and vasculature. Virtually all the labeled debris was removed between 17 and 28 days following the application of cobalt. The rapidity with which the axons were removed suggests that the cobalt accelerates the degenerative process either directly, or indirectly by accelerating the arrival of phagocytic cells. Radial glia appeared to play a smaller role in debris elimination. They took up labeled debris to a lesser degree than microglia and were briefly labeled. Interestingly, radial glia did not take up cobalt when it was injected intracranially and diffused through the brain. A previous claim of an axosomatic retinotectal projection to cells deep in the stratum periventriculare of a teleost fish is reinterpreted to represent cobalt within radial glia.

Animals↗
PubMed1989

Distribution of uncrossed axons along the course of the optic nerve and chiasm of rodents.

The distribution of the ipsilaterally projecting population of retinofugal axons has been analyzed following injections of horseradish peroxidase (HRP) into the optic tract of adult hamsters and rats to determine whether the topographical segregation of the cells of origin seen in the retina is maintained by their axons throughout the course of the optic nerve and chiasm. Axons are limited to a roughly appropriate topographic location within the intraorbital course of the nerve but this organization changes at levels progressively closer to the optic chiasm. Immediately rostral to the chiasm labelled profiles are found dispersed across most of the cross-sectional area of the nerve. This dispersal is maintained within the region of the optic chiasm where a complex rearrangement of ipsilaterally projecting axons takes place. The results show that axons are not retinotopically organized along the entire length of the optic nerve. The order of axons changes along the course of the nerve and in the optic chiasm. The change seen within the intracranial course may indicate a chronotopic re-sorting of axons prior to the optic tract where the organization of axons has previously been interpreted as a map of time of axon arrival.

Animals↗
PubMed1990

Organization of retinopetal axons in the optic nerve of the cichlid fish, Herotilapia multispinosa.

We have studied the position and numbers of retinopetal axons in the rainbow cichlid fish, Herotilapia multispinosa, to determine the response of related parts of the brain of fish to the continual addition of new neurons in the retina. The retinopetal axons were traced by using the retrograde tracers HRP and cobaltous lysine and an immunocytochemical probe, antibodies to FMRF amide, the molluscan cardioexcitatory peptide. One population of cells with retinopetal axons was found in the telencephalon (in the nucleus olfactoretinalis) and the other was scattered in the diencephalon. Some of the cells in the nucleus olfactoetinalis with retinopetal axons were FMRF amide positive; antibodies were used to trace the axons of these cells into the retina. All the retinopetal axons, from the nucleus olfactoretinalis and the diencephalon, were confined to the portion of the optic nerve that contains axons from the central retinal ganglion cells, that is, the oldest ganglion cells. This result suggests that the retinopetal axons grow into the optic nerve and retina early in the life of the fish, and no new ones are added later in life despite the extensive addition of cells in the retina. Counts of the cells in the nucleus olfactoretinalis that project to the retina in 3-month-old and adult fish support this interpretation. We conclude that retinopetal axons grow into the retina early in the life of the fish and respond to the formation of new retina by extending their arbors toward the new retina.

Animals↗
PubMed1995

Expression of chondroitin sulfate and keratan sulfate proteoglycans in the path of growing retinal axons in the developing chick.

Previous investigations have identified proteoglycans in the central nervous system during development and have implicated some proteoglycans as axon guidance molecules that act by inhibiting axon extension. The present study investigated the pattern of immunoreactivity for several glycosaminoglycans common to certain proteoglycans relative to growing retinal axons in the developing chick visual system and in retinal explant cultures. Immunostaining for chondroitin-6-sulfate, chondroitin-4-sulfate, and keratan sulfate was observed to colocalize with retinal axons throughout the retinofugal pathway during the entire period of retinal axon growth. The proteoglycan form of collagen IX, however, was only observed in the retina, primarily peripheral to the areas with actively growing axons. The pattern of immunostaining for chondroitin sulfate in tissue sections suggested that the retinal axons might be a source for some of the chondroitin sulfate immunostaining in the developing visual pathway. This was confirmed in that chondroitin sulfate immunostaining was also observed on neurites emanating from cultured retinal explants. These findings indicate that retinal axons grow in the presence of chondroitin sulfate and keratan sulfate proteoglycans and that these proteoglycans in the developing chick visual pathway have functions other than to inhibit axon growth.

Animals↗
PubMed2006

Degeneration of neuronal cell bodies following axonal injury in Wld(S) mice.

The phenotype of Wld(S) ("slow Wallerian degeneration") mice demonstrates prolonged survival of injured axons. However, whether the Wld(S) mutation delays degeneration of the neuronal cell body following axonal injury is unclear. We used a retrograde model of axonal transport failure in Wld(S) mice to test whether the mutant Wld(S) protein has any beneficial effect on the neuronal cell body. Retrograde axonal transport was physically blocked by optic nerve crush and confirmed by the absence of Fluoro-Gold labeling in wild-type and in Wld(S) mice. After this axonal injury, there was marked protection of axonal degeneration in the Wld(S) phenotype, as confirmed by immunohistochemistry and electron microscopy. However, the Wld(S) protein, localized in the nucleus of retinal ganglion cells, did not prevent or delay degeneration of the retinal ganglion cell body, confirmed by TUNEL staining and Fluoro-Gold labeling. These results imply that, after axonal injury, Wallerian degeneration of axons and degeneration of the neuronal cell body have different mechanisms, which are autonomous and independent of each other. Although the Wld(S) phenotype can be used to demonstrate stable enucleate axons, the mutation is unlikely to protect neurons in neurodegenerative diseases in which there is failure of retrograde transport.

Analysis of Variance↗
PubMed1995

Intrinsic differences in axonal growth from crayfish fast and slow motoneurons.

The motoneurons innervating the fast and slow flexor muscles in the abdomen of crayfish form morphologically distinct motor terminals. Axons of the fast flexor (FF) motoneurons, which innervate the large (fast) flexor muscle, produce extensive motor terminal arbors with many branches. Axons of the slow flexor (SF) motoneurons, which innervate the thin (slow) flexor muscle, produce small terminal arbors with many fewer branches. To determine whether intrinsic factors contribute to these differences in terminal arbors, we compared regenerating axonal arbors from these two populations of motoneurons. We used an explant of the crayfish nerve cord in which axons from the FF and SF motoneurons regenerate on a homogeneous substrate. We found that regardless of the substrate, FF motor axons produced arbors with a greater total length and a greater number and density of branches than SF motor axons. These differences in regenerated arbors persisted in defined medium and in the absence of impulse activity, indicating that they result from intrinsic, neuron-specific factors. The greater branching of the FF motor axons may be related to differences in growth cones: growth cones of FF axons were significantly larger with more filopodia than growth cones of SF axons.

Animals↗
PubMed2002

NGF enhances sensory axon growth induced by laminin but not by the L1 cell adhesion molecule.

Neurotrophins and cell adhesion molecules regulate axon guidance, but their potential coordinate interactions are not well defined. In particular, it has been difficult to define the role of signaling from different surface molecules in neurotrophin-induced axon growth because of the strong dependence of embryonic neurons on this class of molecules for survival. We have addressed this issue using Bax deficient neurons, which do not require neurotrophins for survival. The L1 neural cell adhesion molecule and laminin each supported NGF-independent axon growth of cultured sensory neurons from dorsal root ganglia of embryonic Bax(-/-) mice. However, nerve growth factor (NGF) stimulated additional axon growth of sensory neurons on laminin but not on L1 substrates. Inhibition of the small GTPase RhoA by the dominant-negative mutant RhoA(T19N) restored NGF responsiveness of axon growth on L1 to Bax(-/-) neurons. Constitutively activated RhoA(Q63L) did not affect axon growth on L1 but inhibited NGF-stimulated axon growth on laminin. Consistent with the concept that RhoA was downregulated by NGF in neurons on laminin but not L1, the RhoA inhibitor C2IN-C3 toxin stimulated axon growth on L1 in wild-type DRG neurons in NGF. These results demonstrate a novel substrate-dependent regulation of NGF-induced growth of embryonic sensory axons mediated by RhoA GTPase.

ADP Ribose Transferases↗
PubMed1989

Interactions between Schwann cells and CNS axons following a delay in the normal formation of central myelin.

Irradiation of the rat spinal cord during the first postnatal week results in a profound reduction of oligodendrocyte myelin formation in the dorsal funiculi (DF). Despite this absence of myelin, however, axons in the irradiated region in the DF increase in diameter and approximate the size distribution seen in the control spinal cord. By 25 days of age Schwann cells are present in the irradiated DF where they undergo cell division and myelinate the axons. During the early stages of this myelin formation, these intraspinal Schwann cells exhibit a relationship to axons that is somewhat different from that seen in the normal developing peripheral nervous system (PNS). For example, within a given region, intraspinal Schwann cells myelinate axons of large diameter prior to ensheathing bundles of small diameter axons. Additionally, during myelination a Schwann cell will surround a single axon with multiple processes which appear to compete for contact with the axolemma. On axons of larger diameter, the elaboration of these processes is so excessive that it is often difficult to trace them back to the parent Schwann cell. Later, when a single process establishes several spirals about an axon, additional processes are no longer elaborated, and the "extra" processes disappear as myelin formation advances to the stage of compact lamellae. Thereafter, the myelin sheath continues to form in a normal manner. Excess processes have been observed during myelinogenesis in the normal developing PNS, but their frequency in that environment is much less than in the irradiated cord. These observations support the hypothesis that the signal(s) to initiate myelin formation are expressed on the axolemmal surface and are controlled by the neuron. In addition, these observations suggest that the delay in myelination results in an affinity or tropism between axons and Schwann cells which exceeds the level existing at the normal time of myelin formation.

Animals↗
PubMed1990

Glycogen accumulation in axons after stretch injury.

Thin-section cytochemistry has been used to demonstrate the formation of glycogen deposits within axons after stretch injury to the optic nerve of adult guinea pigs in a model of focal axonal injury. Glycogen deposits occurred within 17% of structurally normal but, we suggest, damaged fibres within the stretched optic nerve. Adjacent fibres did not stain for glycogen. Small numbers of beta glycogen particles were present 15 min after injury within damaged axons and increasing numbers of particles occurred until 72 h. Degeneration bulbs formed by 72 h, but beta glycogen particles were sparse within these. By 7-14 days after injury there was a marked reduction in the numbers of glycogen particles within axons. Alpha rosettes of glycogen were infrequent within damaged axons. Deposition of glycogen particles within astrocytes after nerve injury was confirmed. Alpha rosettes of glycogen occurred within astrocytes by 6 h and remained until 14 days after injury. Possible mechanisms for the development of glycogen deposits within damaged axons are discussed in relation to a hypothesized influx of Ca2+ at the time of injury into damaged axons. We suggest that glycogen deposition within reactive axons reflects Ca2+ mediated alteration of glycogen synthase activity and compromized axonal transport.

Animals↗