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Progress in Neurobiology Mar 1993(1) Lamellated glial sheaths surrounding axons, and electrogenetically active axolemmal foci have evolved independently in widely different phyla. In addition to... (Review)
Review
(1) Lamellated glial sheaths surrounding axons, and electrogenetically active axolemmal foci have evolved independently in widely different phyla. In addition to endowing the axons to conduct trains of impulses at a high speed, myelination and node formation results in a remarkable saving of space and energy. This is particularly important in the CNS, where space is restricted. Unlike the PNS, most CNS axons are myelinated, and several axons may be myelinated by a single cell. This adds further economy of space and energy. On the other hand the high level of complexity of the CNS white matter makes it vulnerable. There are several different kinds of disease affecting myelinated fibre tracts, particularly with respect to CNS white matter. (2) The CNS node of Ranvier presents a more complex structure the larger the fibre. The constricted nodal axon is encircled by perinodal astrocytic processes which contain large gliosomes and emit delicate processes towards the nodal axolemma. One astrocyte may project to several nodes. The node gap contains a polyanionic extracellular material. (3) Lamellated myelinoid bodies are frequent along paranodes of large myelinated CNS fibres. These bodies probably form through budding off from the paranodal myelin sheath. Similar bodies are seen inside astrocytes and microglia. The observation that these bodies are Marchi-positive and argyrophilic, and the presence of acid phosphatase activity around myelinoid bodies inside microglia suggests that they might represent degenerating myelin quanta, involved in the turnover of large myelin sheaths. This putative quantal release and breakdown of myelin material must be compensated for by a production of new myelin at other sites. Therefore, myelination may be viewed as a process that continues throughout life. (4) Biochemical analysis of a sub-cellular fraction enriched in myelinoid bodies shows that these bodies have a composition basically similar to that of myelin. However, breakdown products of myelin constituents, as well as exotic high molecular substances, not present in conventional myelin, can also be found. In addition, the myelinoid body fraction contains proteolytic activity. Studies using isotope labelling of myelin proteins show a source-product relation between myelin and myelinoid bodies. Altogether these data strongly support the hypothesis that myelinoid bodies reflect the catabolic side of myelin turnover. (5) Axons in the nerve fibre layer of the adult rat retina are all unmyelinated, although their diameters range up to over 2 microns. These axons exhibit focally differentiated axolemmal areas. At these sites the axolemma presents a dense undercoating with externally associated Müller cell processes or astrocytic processes.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Animals; Axons; Central Nervous System; Humans; Microscopy, Electron; Myelin Proteins; Myelin Sheath; Nerve Fibers, Myelinated; Nerve Tissue Proteins; Neuroglia; Retina
PubMed: 8441812
DOI: 10.1016/0301-0082(93)90015-k -
Brain Research Feb 1987The distribution of cholesterol in axonal membrane of developing rat optic nerves prior to myelination was studied by freeze-fracture cytochemistry. Binding of the...
The distribution of cholesterol in axonal membrane of developing rat optic nerves prior to myelination was studied by freeze-fracture cytochemistry. Binding of the cholesterol-specific probe, filipin, to the axolemma of premyelinated axons was heterogeneous; this suggests the presence of microdomains of axolemma with different membrane composition and/or cytoskeletal/extracellular matrix association. Although the reasons for this binding pattern have not yet been determined, heterogeneity occurs prior to association of glia with the axon, and may reflect regional differences in lipid/sterol composition of the axonal membrane bilayer, or distribution of membrane-associated cytoskeleton. The distribution of intramembranous particles was not obviously associated with the pattern of filipin binding in early developing axons, however, as might have been expected from the attending differences in fluidity of the membrane microdomains. Microheterogeneity in axonal membranes of developing axons could have an influence on several membrane properties, and may be associated with processes important for growth and differentiation of axons.
Topics: Aging; Animals; Axons; Cholesterol; Filipin; Freeze Fracturing; Histocytochemistry; Intracellular Membranes; Myelin Sheath; Optic Nerve; Polyenes; Rats; Rats, Inbred Strains
PubMed: 3567567
DOI: 10.1016/0006-8993(87)91351-5 -
Journal of Neurology, Neurosurgery, and... Nov 2015Peripheral nerve diseases are traditionally classified as demyelinating or axonal. It has been recently proposed that microstructural changes restricted to the... (Review)
Review
Peripheral nerve diseases are traditionally classified as demyelinating or axonal. It has been recently proposed that microstructural changes restricted to the nodal/paranodal region may be the key to understanding the pathophysiology of antiganglioside antibody mediated neuropathies. We reviewed neuropathies with different aetiologies (dysimmune, inflammatory, ischaemic, nutritional, toxic) in which evidence from nerve conductions, excitability studies, pathology and animal models, indicate the involvement of the nodal region in the pathogenesis. For these neuropathies, the classification in demyelinating and axonal is inadequate or even misleading, we therefore propose a new category of nodopathy that has the following features: (1) it is characterised by a pathophysiological continuum from transitory nerve conduction block to axonal degeneration; (2) the conduction block may be due to paranodal myelin detachment, node lengthening, dysfunction or disruption of Na(+) channels, altered homeostasis of water and ions, or abnormal polarisation of the axolemma; (3) the conduction block may be promptly reversible without development of excessive temporal dispersion; (4) axonal degeneration, depending on the specific disorder and its severity, eventually follows the conduction block. The term nodopathy focuses to the site of primary nerve injury, avoids confusion with segmental demyelinating neuropathies and circumvents the apparent paradox that something axonal may be reversible and have a good prognosis.
Topics: Humans; Myelin Sheath; Nerve Degeneration; Neural Conduction; Peripheral Nervous System Diseases
PubMed: 25699569
DOI: 10.1136/jnnp-2014-310097 -
Annals of Neurology Oct 1996The acute motor axonal neuropathy (AMAN) form of the Guillain-Barre syndrome is a paralytic disorder of abrupt onset characterized pathologically by motor nerve fiber...
The acute motor axonal neuropathy (AMAN) form of the Guillain-Barre syndrome is a paralytic disorder of abrupt onset characterized pathologically by motor nerve fiber degeneration of variable severity and by sparing of sensory fibers. There is little demyelination or lymphocytic inflammation. Most cases have antecedent infection with Campylobacter jejuni and many have antibodies directed toward GM1 ganglioside-like epitopes, but the mechanism of nerve-fiber injury has not been defined. In 7 fatal cases of AMAN, immunocytochemistry demonstrated the presence of IgG and the complement activation product C3d bound to the axolemma of motor fibers. The most frequently involved site was the nodal axolemma, but in more severe cases IgG and C3d were found within the periaxonal space of the myelinated internodes, bound to the outer surface of the motor axon. These results suggest that AMAN is a novel disorder caused by an antibody- and complement-mediated attack on the axolemma of motor fibers.
Topics: Acute Disease; Adolescent; Adult; Axons; Campylobacter jejuni; Child, Preschool; Complement Activation; Complement C3d; Demyelinating Diseases; Female; G(M1) Ganglioside; Humans; Immunoglobulin G; Immunohistochemistry; Male; Middle Aged; Motor Neuron Disease; Nerve Degeneration; Severity of Illness Index
PubMed: 8871584
DOI: 10.1002/ana.410400414 -
Current Topics in Membranes 2019
Review
Topics: Animals; Axons; Cell Membrane; Humans
PubMed: 31610861
DOI: 10.1016/bs.ctm.2019.07.007 -
The Journal of Cell Biology Jan 1981The insertion of axonally transported fucosyl glycoproteins into the axolemma of regenerating nerve sprouts was examined in rat sciatic motor axons at intervals after...
The insertion of axonally transported fucosyl glycoproteins into the axolemma of regenerating nerve sprouts was examined in rat sciatic motor axons at intervals after nerve crush. [(3)H]Fucose was injected into the lumbar ventral horns and the nerves were removed at intervals between 1 and 14 d after labeling. To follow the fate of the "pulse- labeled" glycoproteins, we examined the nerves by correlative radiometric and EM radioautographic approaches. The results showed, first, that rapidly transported [(3)H]fucosyl glycoproteins were inserted into the axolemma of regenerating sprouts as well as parent axons. At 1 d after delivery, in addition to the substantial mobile fraction of radioactivity still undergoing bidirectional transport within the axon, a fraction of label was already associated with the axolemma. Insertion of labeled glycoproteins into the sprout axolemma appeared to occur all along the length of the regenerating sprouts, not just in sprout terminals. Once inserted, labeled glycoproteins did not undergo extensive redistribution, nor did they appear in sprout regions that formed (as a result of continued outgrowth) after their insertion. The amount of radioactivity in the regenerating nerves decreased with time, in part as a result of removal of transported label by retrograde transport. By 7-14 d after labeling, radioautography showed that almost all the remaining radioactivity was associated with axolemma. The regenerating sprouts retained increased amounts of labeled glycoproteins; 7 or 14 d after labeling, the regenerating sprouts had over twice as much of radioactivity as comparable lengths of control nerves or parent axons. One role of fast axonal transport in nerve regeneration is the contribution to the regenerating sprout of glycoproteins inserted into the axolemma; these membrane elements are added both during longitudinal outgrowth and during lateral growth and maturation of the sprout.
Topics: Animals; Axonal Transport; Axons; Female; Fucose; Glycoproteins; Nerve Fibers, Myelinated; Nerve Regeneration; Rats; Sciatic Nerve
PubMed: 6162852
DOI: 10.1083/jcb.88.1.205 -
Brain Research Dec 1981The macromolecular organization of membranes isolated from the rabbit optic nerve and tract was analyzed using the freeze-fracture technique. A myelin fraction and two...
The macromolecular organization of membranes isolated from the rabbit optic nerve and tract was analyzed using the freeze-fracture technique. A myelin fraction and two axolemma-enriched fractions were prepared from a preparation of myelinated axons isolated by flotation in a buffered salt-sucrose medium. In the myelinated axon preparation, axolemma and myelin membranes were easily identified. Larger areas of the axon membrane and myelin membrane totally lacked intramembranous particles. The particles remaining on the myelin membrane formed patches of evenly distributed elongated and globular particles. In contrast, the particles remaining on the axolemma were globular in shape and tightly clustered. Particle clustering and particle-free areas were not characteristic of either the axolemma or myelin membrane of whole nerves fixed in situ and processed for freeze-fracture. The isolated myelin membrane fraction contained a large number of vesicles completely lacking intramembranous particles. Of the remaining membrane vesicles, profiles with dispersed elongated and globular particles predominated. A small percentage of vesicles displayed intramembranous particles of the same size, shape and clustering pattern as that seen on the axolemma of the myelinated axon preparation. The two axolemma fractions were enriched in membrane containing tightly clustered globular particles. Particle-free vesicles as well as some myelin membrane vesicles were also seen in the axolemma fractions.
Topics: Animals; Axons; Cell Fractionation; Freeze Fracturing; Myelin Proteins; Myelin Sheath; Neurilemma; Optic Nerve; Rabbits
PubMed: 7306816
DOI: 10.1016/0006-8993(81)90996-3 -
Neural Regeneration Research Apr 2016The management of traumatic peripheral nerve injury remains a considerable concern for clinicians. With minimal innovations in surgical technique and a limited number of... (Review)
Review
The management of traumatic peripheral nerve injury remains a considerable concern for clinicians. With minimal innovations in surgical technique and a limited number of specialists trained to treat peripheral nerve injury, outcomes of surgical intervention have been unpredictable. The inability to manipulate the pathophysiology of nerve injury (i.e., Wallerian degeneration) has left scientists and clinicians depending on the slow and lengthy process of axonal regeneration (~1 mm/day). When axons are severed, the endings undergo calcium-mediated plasmalemmal sealing, which limits the ability of the axon to be primarily repaired. Polythethylene glycol (PEG) in combination with a bioengineered process overcomes the inability to fuse axons. The mechanism for PEG axonal fusion is not clearly understood, but multiple studies have shown that a providing a calcium-free environment is essential to the process known as PEG fusion. The proposed mechanism is PEG-induced lipid bilayer fusion by removing the hydration barrier surrounding the axolemma and reducing the activation energy required for membrane fusion to occur. This review highlights PEG fusion, its past and current studies, and future directions in PEG fusion.
PubMed: 27212898
DOI: 10.4103/1673-5374.180724 -
The Journal of Cell Biology May 1986In the preceding paper (Kobayashi, T., S. Tsukita, S. Tsukita, Y. Yamamoto, and G. Matsumoto, 1986, J. Cell Biol., 102:1710-1725), we demonstrated biochemically that the...
In the preceding paper (Kobayashi, T., S. Tsukita, S. Tsukita, Y. Yamamoto, and G. Matsumoto, 1986, J. Cell Biol., 102:1710-1725), we demonstrated biochemically that the subaxolemmal cytoskeleton of the squid giant axon was highly specialized and mainly composed of tubulin, actin, axolinin, and a 255-kD protein. In this paper, we analyzed morphologically the molecular organization of the subaxolemmal cytoskeleton in situ. For thin section electron microscopy, the subaxolemmal cytoskeleton was chemically fixed by the intraaxonal perfusion of the fixative containing tannic acid. With this fixation method, the ultrastructural integrity was well preserved. For freeze-etch replica electron microscopy, the intraaxonally perfused axon was opened and rapidly frozen by touching its inner surface against a cooled copper block (4 degrees K), thus permitting the direct stereoscopic observation of the cytoplasmic surface of the axolemma. Using these techniques, it became clear that the major constituents of the subaxolemmal cytoskeleton were microfilaments and microtubules. The microfilaments were observed to be associated with the axolemma through a specialized meshwork of thin strands, forming spot-like clusters just beneath the axolemma. These filaments were decorated with heavy meromyosin showing a characteristic arrowhead appearance. The microtubules were seen to run parallel to the axolemma and embedded in the fine three-dimensional meshwork of thin strands. In vitro observations of the aggregates of axolinin and immunoelectron microscopic analysis showed that this fine meshwork around microtubules mainly consisted of axolinin. Some microtubules grazed along the axolemma and associated laterally with it through slender strands. Therefore, we were led to conclude that the axolemma of the squid giant axon was specialized into two domains (microtubule- and microfilament-associated domains) by its underlying cytoskeletons.
Topics: Actin Cytoskeleton; Animals; Axons; Cell Compartmentation; Cytoskeleton; Decapodiformes; Freeze Etching; Hydrolyzable Tannins; Microscopy, Electron; Microtubule-Associated Proteins; Microtubules; Nerve Tissue Proteins; Neurilemma
PubMed: 3700475
DOI: 10.1083/jcb.102.5.1710 -
Journal of Neurocytology Aug 1985Axolemma-enriched and myelin-enriched fractions were prepared from bovine CNS white matter and conjugated to fluorescein isothiocyanate (FITC). Both unlabelled and...
Axolemma-enriched and myelin-enriched fractions were prepared from bovine CNS white matter and conjugated to fluorescein isothiocyanate (FITC). Both unlabelled and FITC-labelled axolemma and myelin were mitogenic for cultured rat Schwann cells. Treatment of Schwann cells with the FITC-labelled mitogens for up to 24 h resulted in two distinct morphological appearances. FITC-myelin-treated cells were filled with numerous round, fluorescent-labelled intracellular vesicles, while FITC-axolemma-treated cells appeared to be coated with a patchy, ill-defined fluorescence, primarily concentrated around the cell body but extending onto the cell processes. These observations were corroborated under phase microscopy. Electron microscopy revealed multiple, membrane-bound, membrane-containing phagosomes within myelin-treated cells and to a far lesser extent in axolemma-treated cells. The effect on the expression of the myelin-mediated and axolemma-mediated mitogenic signal when Schwann cells were treated with the lysosomal inhibitors, ammonium chloride and chloroquine, was evaluated. The mitogenicity of myelin was reduced 70-80% by these agents whereas the mitogenicity of axolemma was not significantly altered under these conditions. These results suggest that axolemma and myelin stimulate the proliferation of cultured Schwann cells by different mechanisms. Myelin requires endocytosis and lysosomal processing for expression of its mitogenic signal; in contrast, the mitogenicity of axolemma may be transduced at the Schwann cell surface.
Topics: Animals; Axons; Cattle; Cell Division; Cell Membrane; Cells, Cultured; Chloroquine; Fluorescein-5-isothiocyanate; Fluoresceins; Lysosomes; Microscopy, Electron; Myelin Sheath; Rats; Schwann Cells; Thiocyanates
PubMed: 3934342
DOI: 10.1007/BF01200801