Non-compact Myelin Research Articles

Quantification of myelin basic protein in the human fetal spinal cord during the midtrimester of gestation.

The amount of myelin basic protein (MBP) was quantified in human fetal spinal cords from 12 to 24 gestational weeks (GW). MBP expression was determined by Northern blot, quantitative immunoblot, and immunocytochemistry. The development of compact myelin was analyzed by electron microscopy. Thirty-eight human fetal spinal cords were obtained after elective termination of intrauterine pregnancies from healthy women. Northern blot analysis showed a 15.8-fold increase in MBP mRNA between 12 and 18 GW. From 18 to 24 GW, MBP mRNA increased by 2.2-fold. The mRNA data paralleled immunoblot results that showed a 90.5-fold increase in MBP (0.147 ng/mg to 13.3 ng/mg tissue) between 12 and 18 GW and an approximately 11.5-fold increase between 18 and 24 GW (13.3 ng/mg to 154 ng/mg tissue). Immunocytochemical analysis also showed increased staining for MBP with advancing gestational age. At 12 GW, MBP immunoreactivity was observed in all three spinal cord funiculi. By 18 GW, MBP was expressed throughout the spinal cord white matter with the exception of the lateral corticospinal tracts and in the rostral levels of the fasciculus gracilis. With respect to myelin, at 12 GW, rare, noncompacted myelin lamellae were observed by electron microscopy. By 18 GW, discrete areas of compact myelin were observed in areas that showed MBP immunoreactivity, and at 24 GW, compact myelin was prominent throughout the white matter of the spinal cord. This study demonstrates a quantitative increase in MBP expression that is associated with myelin formation during the second trimester of human gestation. This information may provide normative data that can aid in the diagnosis of myelin disorders of the preterm, neonatal, and pediatric spinal cord.

Myelin-associated glycoprotein is not detectable in perikaryal myelin of spiral ganglion neurons of adult mice.

The expression of the adhesion molecules N-CAM (neural cell adhesion molecule), L1, myelin-associated glycoprotein (MAG), and P0 has been investigated by postembedding-immunoelectron microscopy in spiral ganglia of adult mice in which both axons and neuronal cell bodies are myelinated. L1 was absent from both axonal and perikaryal myelin of spiral ganglion neurons but was expressed on unmyelinated nerve fibers. P0 was expressed in compacted parts of both types of myelin but was absent from non-compacted myelin. MAG was not detectable in perikaryal myelin but was strongly expressed in axonal myelin both periaxonally and in non-compacted regions. Conversely, N-CAM was detectable at the interface between myelin and neuronal perikarya and in non-compacted regions of perikaryal myelin, whereas it was hardly detectable in axonal myelin. This inverse expression of MAG and N-CAM in perikaryal and axonal myelin points to the possibility that N-CAM may functionally replace MAG in perikaryal myelin of spiral ganglion neurons.

Expression and functional roles of neural cell surface molecules and extracellular matrix components during development and regeneration of peripheral nerves

By combining both immunocytochemical and functional investigations, a hypothetical framework will be developed for the molecular mechanisms underlying neuron-glia interactions during development and regeneration of peripheral nerves. In particular, the immunoglobulin-like molecules L1, N-CAM, MAG and P0, the extracellular matrix molecules laminin and tenascin, and the carbohydrates PSA and L2/HNK-1 will be considered. During early stages of limb bud innervation in embryos, L1 and N-CAM are expressed on axons and Schwann cells and are involved in axonal fasciculation, whereas tenascin is thought to be involved in forming a scaffold around the nerve possibly preventing axons and/or Schwann cells from leaving the nerve. PSA has been shown to be involved in pathway selection at initial stages of limb bud innervation. Later on, when motor axons enter muscles, the carbohydrates determine the branching pattern of the nerves. During myelination, L1 appears to play a pivotal role during the formation of the first Schwann cell loops around the prospective myelin-containing axons. MAG and P0 appear also to be functionally involved at initial stages of myelin formation. Additionally, MAG may contribute to the formation and maintenance of non-compacted myelin and axon-Schwann cell apposition whereas P0 is involved in myelin compaction. Under regenerative conditions, L1, N-CAM, laminin, and tenascin are strongly up-regulated by denervated Schwann cells. In vitro observations strongly suggest that these molecules might foster axonal regeneration. The carbohydrate PSA is confined to regrowing axons and is also a candidate to support axonal regrowth. L2/HNK-1, which is found on motor axon-associated Schwann cells, may provide regenerating motor axons with a selective advantage over others resulting in appropriate reinnervation of motor pathways. Since many of the functional studies this review refers to have been performed in vitro, some of the conclusions drawn need reexamination in vivo. Gene manipulations, such as the generation of null mutants followed by a thorough morphological and immunocytochemical investigation may be a powerful tool to resolve this problem.

Effects of ethanol exposure on myelination and axon numbers in the L2 dorsal root of the neonatal rat.

Previous studies have demonstrated that exposure to ethanol during development delays the rate at which axons in certain central nervous system tracts acquire myelin. This delay appears to be related to an alteration in oligodendrocyte function and not to an aberrancy in axon size or number. The present study was designed to determine if alterations similar to those observed in the central nervous system also occur in peripheral nerves, specifically the L2 dorsal root. Dams were fed either an ethanol-containing or control liquid diet 2 weeks prior to pregnancy and throughout gestation. The pups born to the pregnant dams were artificially reared from postnatal day (PD) 4 to PD 10 on a similar ethanol-containing or control diet. The pups were sacrificed on PD 10, L2 dorsal roots removed and processed for electron microscopy. The numbers of axons in various states of myelination were quantified. No difference was observed in the number of unmyelinated axons in the L2 dorsal roots from ethanol-exposed and control pups. In roots from ethanol-exposed pups, there was a significant decrease in the number of axons possessing myelin arranged in compact lamellae, but a significant increase in the number of axons surrounded by myelin lamellae in which the Schwann cell cytoplasm had not yet been extruded (noncompact). However, when the number of axons possessing noncompact myelin and a compact myelin sheath were summed, no significant difference was observed. These data suggest that the delay in myelination following ethanol exposure may be a ubiquitous phenomenon throughout the nervous system.

Immunohistological localization of the adhesion molecules L1, N‐CAM, and MAG in the developing and adult optic nerve of mice

The localization of the cell adhesion molecules L1, neural cell adhesion molecule (N-CAM), and myelin-associated glycoprotein (MAG) was studied immunohistologically at the light and electron microscopic levels and immunochemically in the developing and adult mouse optic nerve and retina. The neural adhesion molecule L1 is strongly expressed on the shafts of fasciculating unmyelinated axons at all ages studied from embryonic day 15 through adulthood. Growth cones of retinal ganglion cell axons were weakly L1-positive or L1-negative when contacting glial cells. Unmyelinated axons were not only L1-positive when contacting each other but also when contacting glia, whereas contacts between glial cells were L1-negative at all developmental unmyelinated retinal nerve fiber layer or in the unmyelinated optic nerve head became L1-negative when enwrapped by myelin in the optic nerve proper. At all stages of development N-CAM showed profuse labeling on fasciculating axons, growth cones, and their contact sites with glial cells as well as contacts between glial cells. In contrast to L1, axons remained N-CAM-positive when becoming myelinated. Sometimes, N-CAM was found in compact myelin. However, N-CAM was absent from glial surfaces contacting basement membranes at the interface to meninges, blood vessels, and the vitreous body of the eye. MAG was first detectable intracellularly in oligodendrocytes associated with the endoplasmic reticulum and Golgi apparatus before it became apparent at the cell surface. There it was present on oligodendrocytes prior and during the first stages of ensheathment of axons, both on cell body and processes. After formation of compact myelin MAG remained strongly expressed periaxonally and was only weakly detectable in noncompacted myelin including inner mesaxon and paranodal loops. None of the adhesion molecules was detectable on extracellular matrix, in the meninges, or on endothelial cells. Immunochemical analysis of antigen expression at different developmental stages was in agreement with the immunohistological data. We infer from these observations that L1 is involved in stabilization not only of axon-axon, but also axon-glia contacts, while the more dynamic structure of the growth cone generally expresses less L1. A differential expression of L1 along the course of an axon--being present on its unmyelinated, but absent on its myelinated part--further supports the notion that L1 may be involved in the stabilization of axonal fascicles but not of axon-myelin contacts.(ABSTRACT TRUNCATED AT 400 WORDS)

Common IgA and IgM rheumatoid factor idiotypes in autoimmune diseases.

Anti-idiotypic antibodies to four monoclonal IgM, one polyclonal IgM, and one polyclonal IgA rheumatoid factors were produced in rabbits and tested for cross reactivity with rheumatoid factors from nine patients with essential mixed cryoglobulinaemia, three patients with rheumatoid arthritis, four patients with systemic sicca syndrome, and one patient with systemic lupus erythematosus. Variable (3/16 to 10/16) cross reactivity for each anti-idiotypic antibody was observed which was not restricted by disease category, clonality, or isotype of the rheumatoid factor. These findings suggest that rheumatoid factor genes are highly conserved from the germ-line antibody repertoire.

Multiple exercise-related mononeuropathy with abdominal colic

Hereditary neuropathy with liability to pressure palsies (NLPP) is a rare disease characterized by recurrent sensory-motor deficits precipitated by exposure to minor pressure. This report describes a variant of this neuropathy in 5 siblings suffering from painful palsies after strenuous work with concurrent episodes of abdominal colic resembling that of acute intermittent porphyria. Electrophysiological studies of the index case showed the typical abnormalities of motor and sensory nerve conduction, including clinically non-affected nerves. Light and electron-microscopic examination showed the characteristic lesions of the NLPP with sausage-like swelling of the myelin sheaths. In addition, non-compacted, “loose” myelin lamellae were frequently observed in association with distended Schmidt-Lantermann incisures. Non-compacted myelin was a prominent finding in this type of demyelinating neuropathy. We suggest that an unknown metabolic factor may induce both demyelination of peripheral nerve fibers and functional disturbance in autonomic nerves leading to attacks of abdominal pain.

Undernutrition in the developing rat: effect upon myelination

Long-Evans rats were undernourished from birth by removing the mother from the sucling rats for part of each day; the undernutrition was continued after weaning till 60 days of age by restricting the daily food intake. Brain development was monitored by histologic and selected biochemical analyses coordinated with an ultrastructural morphometric analysis of the pyramidal tract of 30-day-old rats. Brain and body growth were already reduced after 10 days of undernutrition. At 20 days of age, the peak of myelination in the controls, the body and brain weights of the undernourished rats, compared to the controls, were reduced by 25 and 60%, respectively, and by the end of the study (60 days), the brain and body weights were reduced by 30 and 70%, respectively. Morphometric analysis indicated that the proportion of myelinated axons was significantly reduced in starved (34%) relative to control (43%) animals. Fiber analysis revealed that not only were the myelin sheaths thinner in the undernourished rats, but that the sheath was disproportionately reduced relative to the axon diameter. Chemical analysis on a whole brain basis demonstrated a greater than 60% deficit in the relatively myelin-specific galactolipids. (Whole brain analysis included regions more severely affected than the morphometrically analyzed pyramidal tract.) We also obtained evidence for both a delay in the initiation and a general retardation of myelinogenesis. The promyelinating fibers (axons with one or two non-compacted myelin lamellae) still constituted 4.5% of the myelinated fibers in the undernourished animals at 30 days but had declined to 0.3% in the controls. Analysis of the fabtty acids of cerebroside and sulfatide (lipids enriched in myelin) demonstrated in the undernourished group a pattern characteristic of a younger animal. Thus, the effect of undernutrition on the developing rat appears to be one of inhibited and somewhat retarded myelination. These effects were most likely due to a reduction in the number of myelinating glia formed and the restricted capacity of those which form to generate myeline lamellae.