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1

Glutamate excitotoxicity inflicts paranodal myelin splitting and retraction.  

UK PubMed Central (United Kingdom)

Paranodal myelin damage is observed in white matter injury. However the culprit for such damage remains unknown. By coherent anti-Stokes Raman scattering imaging of myelin sheath in fresh tissues with sub-micron resolution, we observed significant paranodal myelin splitting and retraction following glutamate application both ex vivo and in vivo. Multimodal multiphoton imaging further showed that glutamate application broke axo-glial junctions and exposed juxtaparanodal K+ channels, resulting in axonal conduction deficit that was demonstrated by compound action potential measurements. The use of 4-aminopyridine, a broad-spectrum K+ channel blocker, effectively recovered both the amplitude and width of compound action potentials. Using CARS imaging as a quantitative readout of nodal length to diameter ratio, the same kind of paranodal myelin retraction was observed with applications of Ca2+ ionophore A23187. Moreover, exclusion of Ca2+ from the medium or application of calpain inhibitor abolished paranodal myelin retraction during glutamate exposure. Examinations of glutamate receptor agonists and antagonists further showed that the paranodal myelin damage was mediated by NMDA and kainate receptors. These results suggest that an increased level of glutamate in diseased white matter could impair paranodal myelin through receptor-mediated Ca2+ overloading and subsequent calpain activation.

Fu Y; Sun W; Shi Y; Shi R; Cheng JX

2009-01-01

2

Sulfatide decrease in myelin influences formation of the paranodal axo-glial junction and conduction velocity in the sciatic nerve.  

UK PubMed Central (United Kingdom)

Cerebroside sulfotransferase (CST) catalyzes the production of sulfatide, which is one of the major glycolipids in myelin. Homozygous CST knockout mice were shown to be completely deficient in sulfatide. They were born healthy but began to display progressive neurological deficits from 6 weeks of age. Severe abnormalities of paranodal regions and changes in axonal ion channel distribution were prominent in both the central and peripheral nervous systems. But whether partial decreases in myelin sulfatide levels influence paranodal formation, as well as nerve conduction velocity (NCV), is largely unknown. To determine the functional significance of sulfatide content in myelin, we performed electrophysiological, morphological, and biochemical analyses using heterozygote, homozygote, and wild-type mouse peripheral nerves and compared the results with individual sulfatide content. NCVs were significantly reduced in homozygote animals compared with wild-type mice. In contrast, these values were markedly varied in individual heterozygote mice. On the basis of NCV values, we divided heterozygous mice into two groups: mice with mild but significant reduction of NCV and those with normal NCV. Teased nerve fibers obtained from individual mouse sciatic nerves were immunostained, and Na(+) channel and Caspr cluster lengths were measured to determine abnormal levels of junctional formation at the paranode. Furthermore, sulfatide content in each sciatic nerve was examined by thin layer chromatography. The results demonstrated significant correlations among sulfatide level, severity of paranodal abnormality, and reduction of NCV. Thus, the fine regulation of myelin sulfatide content by CST is important for normal function of myelinated axons.

Hayashi A; Kaneko N; Tomihira C; Baba H

2013-04-01

3

Motor and sensory neuropathy due to myelin infolding and paranodal damage in a transgenic mouse model of Charcot-Marie-Tooth disease type 1C.  

Science.gov (United States)

Charcot-Marie-Tooth disease type 1C (CMT1C) is a dominantly inherited motor and sensory neuropathy. Despite human genetic evidence linking missense mutations in SIMPLE to CMT1C, the in vivo role of CMT1C-linked SIMPLE mutations remains undetermined. To investigate the molecular mechanism underlying CMT1C pathogenesis, we generated transgenic mice expressing either wild-type or CMT1C-linked W116G human SIMPLE. Mice expressing mutant, but not wild type, SIMPLE develop a late-onset motor and sensory neuropathy that recapitulates key clinical features of CMT1C disease. SIMPLE mutant mice exhibit motor and sensory behavioral impairments accompanied by decreased motor and sensory nerve conduction velocity and reduced compound muscle action potential amplitude. This neuropathy phenotype is associated with focally infolded myelin loops that protrude into the axons at paranodal regions and near Schmidt-Lanterman incisures of peripheral nerves. We find that myelin infolding is often linked to constricted axons with signs of impaired axonal transport and to paranodal defects and abnormal organization of the node of Ranvier. Our findings support that SIMPLE mutation disrupts myelin homeostasis and causes peripheral neuropathy via a combination of toxic gain-of-function and dominant-negative mechanisms. The results from this study suggest that myelin infolding and paranodal damage may represent pathogenic precursors preceding demyelination and axonal degeneration in CMT1C patients. PMID:23359569

Lee, Samuel M; Sha, Di; Mohammed, Anum A; Asress, Seneshaw; Glass, Jonathan D; Chin, Lih-Shen; Li, Lian

2013-01-28

4

Motor and sensory neuropathy due to myelin infolding and paranodal damage in a transgenic mouse model of Charcot-Marie-Tooth disease type 1C.  

UK PubMed Central (United Kingdom)

Charcot-Marie-Tooth disease type 1C (CMT1C) is a dominantly inherited motor and sensory neuropathy. Despite human genetic evidence linking missense mutations in SIMPLE to CMT1C, the in vivo role of CMT1C-linked SIMPLE mutations remains undetermined. To investigate the molecular mechanism underlying CMT1C pathogenesis, we generated transgenic mice expressing either wild-type or CMT1C-linked W116G human SIMPLE. Mice expressing mutant, but not wild type, SIMPLE develop a late-onset motor and sensory neuropathy that recapitulates key clinical features of CMT1C disease. SIMPLE mutant mice exhibit motor and sensory behavioral impairments accompanied by decreased motor and sensory nerve conduction velocity and reduced compound muscle action potential amplitude. This neuropathy phenotype is associated with focally infolded myelin loops that protrude into the axons at paranodal regions and near Schmidt-Lanterman incisures of peripheral nerves. We find that myelin infolding is often linked to constricted axons with signs of impaired axonal transport and to paranodal defects and abnormal organization of the node of Ranvier. Our findings support that SIMPLE mutation disrupts myelin homeostasis and causes peripheral neuropathy via a combination of toxic gain-of-function and dominant-negative mechanisms. The results from this study suggest that myelin infolding and paranodal damage may represent pathogenic precursors preceding demyelination and axonal degeneration in CMT1C patients.

Lee SM; Sha D; Mohammed AA; Asress S; Glass JD; Chin LS; Li L

2013-05-01

5

[Myelin  

UK PubMed Central (United Kingdom)

The lipid and protein composition and the metabolic turnover of myelin in the C.N.S., are briefly reported. For a better understanding, it seemed useful to introduce some historical data on the discovery of myelin and to give a morphological description at structural and ultrastructural level.

Andreoli D; Aleo MF; Tarantini M; Marinello E

1978-01-01

6

Axo-Glial Interactions Regulate the Localization of Axonal Paranodal Proteins  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Mice incapable of synthesizing the abundant galactolipids of myelin exhibit disrupted paranodal axo-glial interactions in the central and peripheral nervous systems. Using these mutants, we have analyzed the role that axo-glial interactions play in the establishment of axonal protein distribution in...

Dupree, Jeffrey L.; Girault, Jean-Antoine; Popko, Brian

7

Paranodal junction formation and spermatogenesis require sulfoglycolipids  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Mammalian sulfoglycolipids comprise two major members, sulfatide (HSO3-3-galactosylceramide) and seminolipid (HSO3-3-monogalactosylalkylacylglycerol). Sulfatide is a major lipid component of the myelin sheath and serves as the epitope for the well known oligodendrocyte-marker antibody O4. Seminolipi...

Honke, Koichi; Hirahara, Yukie; Dupree, Jeffrey; Suzuki, Kinuko; Popko, Brian; Fukushima, Kikuro; Fukushima, Junko

8

Disruption of myelination by diagnostic US  

International Nuclear Information System (INIS)

In order to test for possible effects of US on myelination, the authors exposed 20 unanesthetized rat pups to US intensities consistent with those used for imaging a human fetus in utero. The rats were 3-5 days old and at a stage of myelination similar to that of a human fetus of about 4-5 months. Then animals were exposed for 30 minutes to the beam from a 3.5-MHz transducer (ADR 2130 real-time linear array, SPTA intensity of 0.4 mW/cm/sup 2/ and SATA intensity of 0.05 mW/cm/sup 2/). Control animals were bound and placed in the tank but not exposed for 30 minutes, and taken straight from the cage. Some animals were killed and tissues were processed for electron microscopy immediately after exposure, others were killed after recovery periods of up to 24 hours. Enlargements of the periaxonal space was visible with separation of adjacent paranodal loops and disruption of Schwann cell-axonal junctions in all exposed animals. Paranodal demyelination was also noted in several nodes. Nodes exhibiting this microedematous morphology were apparent even after a 24-hour recovery period but were not found in control preparations.

1986-12-05

9

Effects of experimental hypothyroidism on myelin sheath structural organization.  

UK PubMed Central (United Kingdom)

A previous study using the 2'3'cyclic nucleotide 3'phosphodiesterase (CNPase), an oligodendroglial marker that also stain ensheathed fibers, showed a decrease in the number of immunoreactive fibers and a change in the pattern of CNPase immunoreactivity (CNPase+) in hypothyroid animals. CNPase+ fibers, in mature hypothyroid animals, showed a continuous pattern of staining in contrast with a discontinuous one in controls. As CNPase, in adult animals, can be found only in regions in which oligodendrocyte cytoplasm remains as internal, external and paranodal loops, it was suggested that the reduction of thyroid hormone levels leads to a failure in myelin compaction. Previous data showed a higher frequency of some abnormalities in myelin sheath as multiple cytoplasmic loops and redundant myelin profiles in mutant animals that present a failure in myelin compaction. The increase in the frequency of these abnormalities (multiple internal and external loops and redundant myelin) indicates a failure in the interrelations between the axons and the oligodendroglial processes. To verify if the thyroid hormone deficiency during CNS development disturbs these interrelations, we evaluated the frequency of the morphological abnormalities (multiple internal and external loops and redundant myelin) in myelin sheath of corpus callosum (cc) in experimental hypothyroidism. Randomic fields were kept by electron microscopy and the analysis of the frequency of morphological abnormalities showed a significant difference in hypothyroid animals at 60-day-old (PND60), with no significant differences at 90-day-old (PND90) animals. The frequency of multiple internal loops is higher in hypothyroid animals at PND60 that indicates a disturbance in the wrapping by the oligodendroglial process. These findings showed that thyroid hormone might modulate the axon-oligodendroglial relationships that are important for the adequate temporal sequence of events that occur during myelinogenesis, with possible consequences on myelin compaction.

Ferreira AA; Nazário JC; Pereira MJ; Azevedo NL; Barradas PC

2004-03-01

10

Polarization and Myelination in Myelinating Glia  

Science.gov (United States)

Myelinating glia, oligodendrocytes in central nervous system and Schwann cells in peripheral nervous system, form myelin sheath, a multilayered membrane system around axons enabling salutatory nerve impulse conduction and maintaining axonal integrity. Myelin sheath is a polarized structure localized in the axonal side and therefore is supposed to be formed based on the preceding polarization of myelinating glia. Thus, myelination process is closely associated with polarization of myelinating glia. However, cell polarization has been less extensively studied in myelinating glia than other cell types such as epithelial cells. The ultimate goal of this paper is to provide insights for the field of myelination research by applying the information obtained in polarity study in other cell types, especially epithelial cells, to cell polarization of myelinating glia. Thus, in this paper, the main aspects of cell polarization study in general are summarized. Then, they will be compared with polarization in oligodendrocytes. Finally, the achievements obtained in polarization study for epithelial cells, oligodendrocytes, and other types of cells will be translated into polarization/myelination process by Schwann cells. Then, based on this model, the perspectives in the study of Schwann cell polarization/myelination will be discussed.

Masaki, Toshihiro

2012-01-01

11

Oligodendrocyte myelin glycoprotein does not influence node of ranvier structure or assembly.  

UK PubMed Central (United Kingdom)

Oligodendrocyte myelin glycoprotein (OMgp) is expressed by both neurons and oligodendrocytes in the CNS. It has been implicated in growth cone collapse and neurite outgrowth inhibition by signaling through the Nogo receptor and paired Ig-like receptor B (PirB). OMgp was also reported to be an extracellular matrix (ECM) protein surrounding CNS nodes of Ranvier and proposed to function as (1) an inhibitor of nodal collateral sprouting and (2) an important contributor to proper nodal and paranodal architecture. However, we show here that the anti-OMgp antiserum used in previous studies to define the functions of OMgp at nodes is not specific. Among all reported nodal ECM components, the antiserum exhibited strong cross-reactivity against versican V2 isoform, a chondroitin sulfate proteoglycan. Furthermore, the OMgp antiserum labeled OMgp-null nodes, but not nodes from versican V2-deficient mice, and preadsorption of the OMgp antiserum with recombinant versican V2 blocked nodal labeling. Analysis of CNS nodes in OMgp-null mice failed to reveal any nodal or paranodal defects, or increased nodal collateral sprouting, indicating that OMgp does not participate in CNS node of Ranvier assembly or maintenance. We successfully identified a highly specific anti-OMgp antibody and observed OMgp staining in white matter only after initiation of myelination. OMgp immunoreactivity decorated the surface of mature myelinated axons, but was excluded from compact myelin and nodes. Together, our results strongly argue against the nodal localization of OMgp and its proposed functions at nodes, and reveal OMgp's authentic localization relative to nodes and myelin.

Chang KJ; Susuki K; Dours-Zimmermann MT; Zimmermann DR; Rasband MN

2010-10-01

12

Paranode Abnormalities and Oxidative Stress in Optic Nerve Vulnerable to Secondary Degeneration: Modulation by 670 nm Light Treatment.  

UK PubMed Central (United Kingdom)

Secondary degeneration of nerve tissue adjacent to a traumatic injury results in further loss of neurons, glia and function, via mechanisms that may involve oxidative stress. However, changes in indicators of oxidative stress have not yet been demonstrated in oligodendrocytes vulnerable to secondary degeneration in vivo. We show increases in the oxidative stress indicator carboxymethyl lysine at days 1 and 3 after injury in oligodendrocytes vulnerable to secondary degeneration. Dihydroethidium staining for superoxide is reduced, indicating endogenous control of this particular reactive species after injury. Concurrently, node of Ranvier/paranode complexes are altered, with significant lengthening of the paranodal gap and paranode as well as paranode disorganisation. Therapeutic administration of 670 nm light is thought to improve oxidative metabolism via mechanisms that may include increased activity of cytochrome c oxidase. Here, we show that light at 670 nm, delivered for 30 minutes per day, results in in vivo increases in cytochrome c oxidase activity co-localised with oligodendrocytes. Short term (1 day) 670 nm light treatment is associated with reductions in reactive species at the injury site. In optic nerve vulnerable to secondary degeneration superoxide in oligodendrocytes is reduced relative to handling controls, and is associated with reduced paranode abnormalities. Long term (3 month) administration of 670 nm light preserves retinal ganglion cells vulnerable to secondary degeneration and maintains visual function, as assessed by the optokinetic nystagmus visual reflex. Light at a wavelength of 670 nm may serve as a therapeutic intervention for treatment of secondary degeneration following neurotrauma.

Szymanski CR; Chiha W; Morellini N; Cummins N; Bartlett CA; O'Hare Doig RL; Savigni DL; Payne SC; Harvey AR; Dunlop SA; Fitzgerald M

2013-01-01

13

Is myelin a mitochondrion?  

UK PubMed Central (United Kingdom)

It has been hypothesized that myelin acts like a mitochondrion, generating ATP across the membranes of its sheath. By calculating the proton motive force across the myelin membrane based on known values for the pH and membrane potential of the oligodendrocyte, we find that insufficient energy could be harvested from proton flow across the myelin membrane to synthesize ATP. In fact, if the respiratory chain were present in the myelin membrane, then the ATP synthase would function in reverse, hydrolyzing rather than synthesizing ATP. This calculation places the hypothesis of an energy-producing role for myelin in considerable doubt.

Harris JJ; Attwell D

2013-01-01

14

Neuregulin-1 and Myelination  

Science.gov (United States)

The trigger for the process of myelin formation during neural development has long been a mystery. Recent studies suggest that this trigger is the growth factor neuregulin-1, expressed on the surface of axons, which signals through ErbB2 and ErbB3 receptors expressed on the surface of myelin-forming glia.

Greg Lemke (The Salk Institute; REV)

2006-03-07

15

Myelin gangliosides in vertebrates.  

UK PubMed Central (United Kingdom)

A phylogenetic survey of brain myelin ganglioside patterns and concentrations has been carried out on 16 vertebrate species. Gangliosides were isolated from purified myelin and found to vary in concentration from 25 micrograms of sialic acid per 100 mg of myelin for goldfish to a value of 395 for turkey. The latter species had approximately equivalent amounts of GM1 and GM4 as the two major gangliosides. The 11 mammals studied all had GM1 as the major ganglioside, with variable amounts of GM4; rhesus monkey and human had 20-25% GM4, whereas the others had less than 10%. Amphibia and fish myelin contained the least total ganglioside, with patterns that showed relatively little GM1 and no detectable GM4. Alligator myelin was unique in having a total concentration as high as the avian species, but a pattern with predominantly di- and trisialo gangliosides.

Cochran FB Jr; Yu RK; Ledeen RW

1982-09-01

16

GM1 improves neurofascin155 association with lipid rafts and prevents rat brain myelin injury after hypoxia-ischemia  

Directory of Open Access Journals (Sweden)

Full Text Available White matter injury characterized by damage to myelin is an important process in hypoxic-ischemic brain damage (HIBD). Because the oligodendrocyte-specific isoform of neurofascin, neurofascin 155 (NF155), and its association with lipid rafts are essential for the establishment and stabilization of the paranodal junction, which is required for tight interaction between myelin and axons, we analyzed the effect of monosialotetrahexosyl ganglioside (GM1) on NF155 expression and its association with lipid rafts after HIBD in Sprague-Dawley rats, weighing 12-15 g, on day 7 post-partum (P7; N = 20 per group). HIBD was induced on P7 and the rats were divided into two groups: one group received an intraperitoneal injection of 50 mg/kg GM1 three times and the other group an injection of saline. There was also a group of 20 sham-operated rats. After sacrifice, the brains of the rats were removed on P30 and studied by immunochemistry, SDS-PAGE, Western blot analysis, and electron microscopy. Staining showed that the saline group had definite rarefaction and fragmentation of brain myelin sheaths, whereas the GM1 group had no obvious structural changes. The GM1 group had 1.9-2.9-fold more GM1 in lipid rafts than the saline group (fraction 3-6; all P < 0.05) and 0.5-2.4-fold higher expression of NF155 in lipid rafts (fraction 3-5; all P < 0.05). Injection of GM1 increased the content of GM1 in lipid rafts as well as NF155 expression and its lipid raft association in HIBD rat brains. GM1 may repair the structure of lipid rafts, promote the association of NF155 (or other important proteins) with lipid rafts, stabilize the structure of paranodes, and eventually prevent myelin sheath damage, suggesting a novel mechanism for its neuroprotective properties.

Y.P. Zhang; Q.L. Huang; C.M. Zhao; J.L. Tang; Y.L. Wang

2011-01-01

17

Potassium channels in nodal and internodal axonal membrane of mammalian myelinated fibres.  

UK PubMed Central (United Kingdom)

Horakova et al. were the first to observe that the phase of late outward current carried by potassium ions in frog and squid nerve is virtually absent in voltage-clamped rat nodes of Ranvier. This observation has been recently confirmed by Chiu et al. in rabbit nodes of Ranvier, suggesting that the nodal membrane in the mammal generally has few if any potassium channels. The present voltage-clamp experiments show that large potassium currents can, however, be produced in normal rabbit nodes of Ranvier by acute treatment designed to loosen the myelin from the axonal membrane. From this we conclude that whereas potassium channels are absent in the mammalian nodal membrane, they are normally present in the internodal axonal membrane at least in the paranodal region.

Chiu SY; Ritchie JM

1980-03-01

18

GM1 improves neurofascin155 association with lipid rafts and prevents rat brain myelin injury after hypoxia-ischemia  

Scientific Electronic Library Online (English)

Full Text Available Abstract in english White matter injury characterized by damage to myelin is an important process in hypoxic-ischemic brain damage (HIBD). Because the oligodendrocyte-specific isoform of neurofascin, neurofascin 155 (NF155), and its association with lipid rafts are essential for the establishment and stabilization of the paranodal junction, which is required for tight interaction between myelin and axons, we analyzed the effect of monosialotetrahexosyl ganglioside (GM1) on NF155 expression a (more) nd its association with lipid rafts after HIBD in Sprague-Dawley rats, weighing 12-15 g, on day 7 post-partum (P7; N = 20 per group). HIBD was induced on P7 and the rats were divided into two groups: one group received an intraperitoneal injection of 50 mg/kg GM1 three times and the other group an injection of saline. There was also a group of 20 sham-operated rats. After sacrifice, the brains of the rats were removed on P30 and studied by immunochemistry, SDS-PAGE, Western blot analysis, and electron microscopy. Staining showed that the saline group had definite rarefaction and fragmentation of brain myelin sheaths, whereas the GM1 group had no obvious structural changes. The GM1 group had 1.9-2.9-fold more GM1 in lipid rafts than the saline group (fraction 3-6; all P

Zhang, Y.P.; Huang, Q.L.; Zhao, C.M.; Tang, J.L.; Wang, Y.L.

2011-06-01

19

Electrodiagnostic testing and histopathologic changes confirm peripheral nervous system myelin abnormalities in the feline model of niemann-pick disease type C.  

UK PubMed Central (United Kingdom)

Niemann-Pick disease type C (NPC disease) is an incurable, neurodegenerative, autosomal recessive disease caused by mutations in either the NPC1 or the NPC2 gene. These mutations affect the intracellular trafficking of lipids and cholesterol, resulting in the intralysosomal accumulation of unesterified cholesterol and glycosphingolipids. These abnormalities are associated with clinical ataxia and impaired motor and intellectual development, and death frequently occurs in adolescence. The incidence of peripheral neuropathy in NPC patients is not known. We investigated peripheral nerves in the naturally occurring feline model of NPC disease, which has proven to be critical for understanding both disease pathogenesis and for evaluating experimental therapies. Electrodiagnostic studies revealed significantly slowed motor and sensory nerve conduction velocities in affected cats in the absence of altered M-wave amplitude. Histologic and ultrastructural analyses showed thin myelin sheaths, membranous debris, myelin figures, lipid vacuolization of Schwann cell cytoplasm, and expanded paranodal areas. Axonal degeneration was not identified. There was a shift to small myelinated fibers in affected cats, and there were significant decreases in fiber diameter, axon diameter, and myelin thickness. These changes were similar to those described in the murine NPC disease model and in rare patients in whom nerve biopsy has been performed. Characterization of the demyelinating neuropathy is necessary for evaluating clinical trials that target only the CNS aspects of NPC.

Bagel JH; Sikora TU; Prociuk M; Pesayco JP; Mizisin AP; Shelton GD; Vite CH

2013-03-01

20

In vivo evidence that TRAF4 is required for central nervous system myelin homeostasis.  

UK PubMed Central (United Kingdom)

Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) are major signal transducers for the TNF and interleukin-1/Toll-like receptor superfamilies. However, TRAF4 does not fit the paradigm of TRAF function in immune and inflammatory responses. Its physiological and molecular functions remain poorly understood. Behavorial analyses show that TRAF4-deficient mice (TRAF4-KO) exhibit altered locomotion coordination typical of ataxia. TRAF4-KO central nervous system (CNS) ultrastructure shows strong myelin perturbation including disorganized layers and disturbances in paranode organization. TRAF4 was previously reported to be expressed by CNS neurons. Using primary cell culture, we now show that TRAF4 is also expressed by oligodendrocytes, at all stages of their differentiation. Moreover, histology and electron microscopy show degeneration of a high number of Purkinje cells in TRAF4-KO mice, that was confirmed by increased expression of the Bax pro-apoptotic marker (immunofluorescence), TUNEL analysis, and caspase-3 activation and PARP1 cleavage (western blotting). Consistent with this phenotype, MAG and NogoA, two myelin-induced neurite outgrowth inhibitors, and their neuron partners, NgR and p75NTR were overexpressed (Q-RT-PCR and western blotting). The strong increased phosphorylation of Rock2, a RhoA downstream target, indicated that the NgR/p75NTR/RhoA signaling pathway, known to induce actin cytoskeleton rearrangement that favors axon regeneration inhibition and neuron apoptosis, is activated in the absence of TRAF4 (western blotting). Altogether, these results provide conclusive evidence for the pivotal contribution of TRAF4 to myelination and to cerebellar homeostasis, and link the loss of TRAF4 function to demyelinating or neurodegenerative diseases.

Blaise S; Kneib M; Rousseau A; Gambino F; Chenard MP; Messadeq N; Muckenstrum M; Alpy F; Tomasetto C; Humeau Y; Rio MC

2012-01-01

 
 
 
 
21

Platelet-derived growth factor-responsive neural precursors give rise to myelinating oligodendrocytes after transplantation into the spinal cords of contused rats and dysmyelinated mice.  

UK PubMed Central (United Kingdom)

Spinal cord injury (SCI) results in substantial oligodendrocyte death and subsequent demyelination leading to white-matter defects. Cell replacement strategies to promote remyelination are under intense investigation; however, the optimal cell for transplantation remains to be determined. We previously isolated a platelet-derived growth factor (PDGF)-responsive neural precursor (PRP) from the ventral forebrain of fetal mice that primarily generates oligodendrocytes, but also astrocytes and neurons. Importantly, human PRPs were found to possess a greater capacity for oligodendrogenesis than human epidermal growth factor- and/or fibroblast growth factor-responsive neural stem cells. Therefore, we tested the potential of PRPs isolated from green fluorescent protein (GFP)-expressing transgenic mice to remyelinate axons in the injured rat spinal cord. PRPs were transplanted 1 week after a moderate thoracic (T9) spinal cord contusion in adult male rats. After initial losses, PRP numbers remained stable from 2 weeks posttransplantation onward and those surviving cells integrated into host tissue. Approximately one-third of the surviving cells developed the typical branched phenotype of mature oligodendrocytes, expressing the marker APC-CC1. The close association of GFP cells with myelin basic protein as well as with Kv1.2 and Caspr in the paranodal and juxtaparanodal regions of nodes of Ranvier indicated that the transplanted cells successfully formed mature myelin sheaths. Transplantation of PRPs into dysmyelinated Shiverer mice confirmed the ability of PRP-derived cells to produce compact myelin sheaths with normal periodicity. These findings indicate that PRPs are a novel candidate for CNS myelin repair, although PRP-derived myelinating oligodendrocytes were insufficient to produce behavioral improvements in our model of SCI.

Plemel JR; Chojnacki A; Sparling JS; Liu J; Plunet W; Duncan GJ; Park SE; Weiss S; Tetzlaff W

2011-12-01

22

Platelet-derived growth factor-responsive neural precursors give rise to myelinating oligodendrocytes after transplantation into the spinal cords of contused rats and dysmyelinated mice.  

Science.gov (United States)

Spinal cord injury (SCI) results in substantial oligodendrocyte death and subsequent demyelination leading to white-matter defects. Cell replacement strategies to promote remyelination are under intense investigation; however, the optimal cell for transplantation remains to be determined. We previously isolated a platelet-derived growth factor (PDGF)-responsive neural precursor (PRP) from the ventral forebrain of fetal mice that primarily generates oligodendrocytes, but also astrocytes and neurons. Importantly, human PRPs were found to possess a greater capacity for oligodendrogenesis than human epidermal growth factor- and/or fibroblast growth factor-responsive neural stem cells. Therefore, we tested the potential of PRPs isolated from green fluorescent protein (GFP)-expressing transgenic mice to remyelinate axons in the injured rat spinal cord. PRPs were transplanted 1 week after a moderate thoracic (T9) spinal cord contusion in adult male rats. After initial losses, PRP numbers remained stable from 2 weeks posttransplantation onward and those surviving cells integrated into host tissue. Approximately one-third of the surviving cells developed the typical branched phenotype of mature oligodendrocytes, expressing the marker APC-CC1. The close association of GFP cells with myelin basic protein as well as with Kv1.2 and Caspr in the paranodal and juxtaparanodal regions of nodes of Ranvier indicated that the transplanted cells successfully formed mature myelin sheaths. Transplantation of PRPs into dysmyelinated Shiverer mice confirmed the ability of PRP-derived cells to produce compact myelin sheaths with normal periodicity. These findings indicate that PRPs are a novel candidate for CNS myelin repair, although PRP-derived myelinating oligodendrocytes were insufficient to produce behavioral improvements in our model of SCI. PMID:22407783

Plemel, Jason R; Chojnacki, Andrew; Sparling, Joseph S; Liu, Jie; Plunet, Ward; Duncan, Greg J; Park, So Eyun; Weiss, Samuel; Tetzlaff, Wolfram

2011-08-23

23

Fate of myelinated fibres in the optic nerves in experimental Creutzfeldt-Jakob disease in rodents: an ultrastructural study.  

UK PubMed Central (United Kingdom)

We report the ultrastructural appearances of myelinated fibres of the optic nerves from mice infected with the Fujisaki strain of Gerstmann-Sträussler-Scheinker (GSS) disease and from Echigo-1 strain of Creutzfeldt-Jakob disease (CJD). Optic nerves from CJD- and GSS-infected rodents showed severe pathological changes. Theses changes were qualitatively indistinguishable from each other but were more robust in the Fujisaki GSS model than in the hamsters inoculated with Echigo-1. The most characteristic finding was the distension with the attenuation of the myelin sheath forming a vacuole while shrunken axon was attached to the innermost layer of the myelin. With high power electron microscopy, we could observe the splitting of the myelin lamellae at the major dense or intraperiod lines to form complex openings that extended to line the vacuole. This finding suggests that myelin lamellae participate in the formation of vacuoles.

Sikorska B; Wali? A; Bratosiewicz-Wasik J; Brown P; Liberski PP

2004-01-01

24

Can't wait to myelinate.  

UK PubMed Central (United Kingdom)

Oligodendrocytes myelinate axons in the central nervous system (CNS). In this issue of Developmental Cell, Czopka et al. (2013) shed light on the temporal control of myelination by individual cells. They demonstrate that oligodendrocytes in vivo have only a brief time window to initiate myelination, which has important implications for CNS plasticity.

Glenn TD; Talbot WS

2013-06-01

25

Dynamics of myelin membrane contacts.  

UK PubMed Central (United Kingdom)

The crystal-like array of membranes in the nerve myelin sheath can be swollen or compacted by controlled changes in the environment. Swelling results when the ionic strength is reduced; compaction occurs when the water activity is lowered or when the divalent cation concentration is raised. X-ray diffraction patterns from frozen specimens show that dehydrating treatments, which induce compaction, are cryoprotective. Electron micrographs of freeze-fractured specimens show that the compacted domains are continuous with normal period arrays. Intramembrane particles, which are uniformly distributed in untreated membranes, are laterally displaced from the compacted membrane layers into particle-enriched domains. The more particle-dense of the alternating rough-surfaced membrane fracture faces is the E-face. The smooth fracture faces of compacted myelin membranes and of purified myelin lipids look the same. Comparison of the electron density profiles indicates that some protein remains associated with the lipid polar groups in compacted arrays. The dynamics of structural changes in myelin provides information about the intermembrane forces that stabilize the regular arrangement.

Caspar DL; Melchior V; Hollingshead CJ; Kirschner DA

1980-01-01

26

Nogo, myelin and axonal regeneration  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Adult mammalian central nervous system (CNS) axons have very limited capacity of regrowth after injury. In recent years, advances in the field of axonal regeneration have proved that neurons do not regenerate, mainly because of the presence of inhibitory molecules. Myelin-associated proteins limit a...

Mingorance Jiménez, Alfredo; Soriano García, Eduardo; Río Fernández, José Antonio del

27

Myelination in very low birth weight infants  

International Nuclear Information System (INIS)

The prognostic significance of cerebral myelination was evaluated with magnetic resonance imaging (MRI) in very low birth weight infants. Myelination was graded in two specified sites, optic radiation and corpus callosum, based on the stages of normal term babies and healthy premature infants. The subjects were 30 preterm infants weighing less than 1,500 gm at birth. MRI was performed at 4 to 7 months (corrected age). The normal myelination stage was seen in 18 cases, while a delayed stage was noticed in 12 cases. In the normal myelination group, only 1 case (6%) had handicaps. In the delayed myelination group, 8 cases (67%) had handicaps. Our results showed that delayed myelination was closely related to a poor prognosis. We believe that MRI would be a very good imaging modality for predicting the outcome of very low birth weight infants, particularly in terms of evaluation of myelination. (author)

1991-01-01

28

Schwann cell myelination requires Dynein function  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Interaction of Schwann cells with axons triggers signal transduction that drives expression of Pou3f1 and Egr2 transcription factors, which in turn promote myelination. Signal transduction appears to be mediated, at least in part, by cyclic adenosine monophosphate (cAMP) because elevation of cAMP levels can stimulate myelination in the absence of axon contact. The mechanisms by which the myelinating signal is conveyed remain unclear. Results By analyzing mutations that disrupt myelination in zebrafish, we learned that Dynein cytoplasmic 1 heavy chain 1 (Dync1h1), which functions as a motor for intracellular molecular trafficking, is required for peripheral myelination. In dync1h1 mutants, Schwann cell progenitors migrated to peripheral nerves but then failed to express Pou3f1 and Egr2 or make myelin membrane. Genetic mosaic experiments revealed that robust Myelin Basic Protein expression required Dync1h1 function within both Schwann cells and axons. Finally, treatment of dync1h1 mutants with a drug to elevate cAMP levels stimulated myelin gene expression. Conclusion Dync1h1 is required for retrograde transport in axons and mutations of Dync1h1 have been implicated in axon disease. Our data now provide evidence that Dync1h1 is also required for efficient myelination of peripheral axons by Schwann cells, perhaps by facilitating signal transduction necessary for myelination.

Langworthy Melissa M; Appel Bruce

2012-01-01

29

Lipidome and proteome map of myelin membranes.  

UK PubMed Central (United Kingdom)

To understand the molecular anatomy of myelin membranes, we performed a large-scale, liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS)-based lipidome and proteome screen on freshly purified human and murine myelin fractions. We identified more than 700 lipid moieties and above 1,000 proteins in the two species, including 284 common lipids and 257 common proteins. This study establishes the first comprehensive map of myelin membrane components in human and mice. Although this study demonstrates many similarities between human and murine myelin, several components have been identified exclusively in each species. Future quantitative validation studies focused on interspecies differences will authenticate the myelin membrane anatomy. The combined lipidome and proteome map presented here can nevertheless be used as a reference library for myelin health and disease.

Gopalakrishnan G; Awasthi A; Belkaid W; De Faria O Jr; Liazoghli D; Colman DR; Dhaunchak AS

2013-03-01

30

Lipidome and proteome map of myelin membranes.  

Science.gov (United States)

To understand the molecular anatomy of myelin membranes, we performed a large-scale, liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS)-based lipidome and proteome screen on freshly purified human and murine myelin fractions. We identified more than 700 lipid moieties and above 1,000 proteins in the two species, including 284 common lipids and 257 common proteins. This study establishes the first comprehensive map of myelin membrane components in human and mice. Although this study demonstrates many similarities between human and murine myelin, several components have been identified exclusively in each species. Future quantitative validation studies focused on interspecies differences will authenticate the myelin membrane anatomy. The combined lipidome and proteome map presented here can nevertheless be used as a reference library for myelin health and disease. PMID:23325434

Gopalakrishnan, Gopakumar; Awasthi, Anshul; Belkaid, Wiam; De Faria, Omar; Liazoghli, Dalinda; Colman, David R; Dhaunchak, Ajit S

2012-11-27

31

Split gland  

Energy Technology Data Exchange (ETDEWEB)

A split gland having only three parts is described. The gland has substantially the same stability to the relative motion of the constituent half-gland members during the attachment process to a female fitting as have more complicated designs. Ease of manufacture and use result from the reduction in complexity of the present invention.

Petranto, Joseph J. (Los Alamos, NM)

1989-01-01

32

Myelin gangliosides: an unusual pattern in the avian central nervous system.  

UK PubMed Central (United Kingdom)

Gangliosides were isolated from purified myelin obtained from brain and spinal cord of mature chickens and pigeons. Total concentrations were approximately two- to fivefold greater than for previously reported mammalian species, and their patterns also differed in containing significantly more sialosylgalactosylceramide (GM4). The latter comprised one-third to one-fourth of total myelin ganglioside, approximately equivalent to GM1 (II3NeuNAcGgOse4Cer). As in mammals, GM4 of avian CNS appeared to be localized in myelin. Fatty acids of this ganglioside included both the hydroxy- and unsubstituted types, and long-chain bases were almost entirely C18. Ganglioside GM1 split into two closely migrating bands on TLC, the slower of which resembled mammalian GM1 in having stearate as the main fatty acid with a measurable amount (10%) of C20-sphingosine; the faster band had predominantly longer-chain fatty acids and very little C20-sphingosine.

Cochran FB Jr; Yu RK; Ando S; Ledeen RW

1981-02-01

33

Splitting Descartes  

DEFF Research Database (Denmark)

Kognition og Pćdagogik vol. 48:10-18. 2003 Short description : The cognitivistic paradigm and Descartes' view of embodied knowledge. Abstract: That the philosopher Descartes separated the mind from the body is hardly news: He did it so effectively that his name is forever tied to that division. But what exactly is Descartes' point? How does the Kartesian split hold up to recent biologically based learning theories?

Schilhab, Theresa

2007-01-01

34

Akt/mTOR signalling in myelination.  

Science.gov (United States)

Akt signalling has emerged as one of the major pathways involved in myelination, implicated in the regulation of several steps during the development of myelinating Schwann cells and oligodendrocytes. One of the main pathways intimately linked with Akt is mTOR [mammalian (or mechanistic) target of rapamycin] signalling. Recent evidence suggests that many processes attributed to the Akt pathway in myelination depend, at least partly, on mTOR signalling. In the present mini-review, we summarize the major aspects of Akt/mTOR signalling and myelination, and how they appear to be linked. We focus on the PNS (peripheral nervous system), but also cover the key points of CNS (central nervous system) myelination, pointing out differences and similarities between the PNS and the CNS. PMID:23863161

Norrmén, Camilla; Suter, Ueli

2013-08-01

35

Akt/mTOR signalling in myelination.  

UK PubMed Central (United Kingdom)

Akt signalling has emerged as one of the major pathways involved in myelination, implicated in the regulation of several steps during the development of myelinating Schwann cells and oligodendrocytes. One of the main pathways intimately linked with Akt is mTOR [mammalian (or mechanistic) target of rapamycin] signalling. Recent evidence suggests that many processes attributed to the Akt pathway in myelination depend, at least partly, on mTOR signalling. In the present mini-review, we summarize the major aspects of Akt/mTOR signalling and myelination, and how they appear to be linked. We focus on the PNS (peripheral nervous system), but also cover the key points of CNS (central nervous system) myelination, pointing out differences and similarities between the PNS and the CNS.

Norrmén C; Suter U

2013-08-01

36

Inborn errors of brain myelin formation.  

Science.gov (United States)

Inborn errors of brain myelin formation or hypomyelinating leukodystrophies (HLD) represent a heterogeneous group of white matter diseases related to a primitive impairment of oligodendrocytes to produce myelin in the central nervous system (CNS). Cerebral magnetic resonance imaging (MRI) allows an assessment of the myelination pattern. The clinical presentation is related to the degree of hypomyelination and its consequences on axonal functions. When the gene defect interferes with the active infantile phase of myelination, the consequences might be severe, with delayed and loss of psychomotor development, absence of myelin signal on cerebral MRI and of identifiable waves on cerebral evoked potentials, as described by Pelizaeus and Merzbacher (PMD). When the pathophysiological mechanism is less severe, myelin production is maintained, although signs of progressive axonopathy are observed, related to progressive spastic paraplegia (SPG) associated with cognitive or behavioral disturbances. HLDs have been classified according to gene defects or associated signs. The X-linked HDL1 (PMD and SPG2) is related to the gene that controls the production of the major CNS myelin proteins, the proteolipid proteins (PLP). The gap junction protein, gamma 2 gene (GJC2) encoding oligodendrocyte-specific connexin, has been shown to be involved in the autosomal recessive HLD2 (PMLD1 and SPG44). PMID:23622380

Boespflug-Tanguy, Odile

2013-01-01

37

Inborn errors of brain myelin formation.  

UK PubMed Central (United Kingdom)

Inborn errors of brain myelin formation or hypomyelinating leukodystrophies (HLD) represent a heterogeneous group of white matter diseases related to a primitive impairment of oligodendrocytes to produce myelin in the central nervous system (CNS). Cerebral magnetic resonance imaging (MRI) allows an assessment of the myelination pattern. The clinical presentation is related to the degree of hypomyelination and its consequences on axonal functions. When the gene defect interferes with the active infantile phase of myelination, the consequences might be severe, with delayed and loss of psychomotor development, absence of myelin signal on cerebral MRI and of identifiable waves on cerebral evoked potentials, as described by Pelizaeus and Merzbacher (PMD). When the pathophysiological mechanism is less severe, myelin production is maintained, although signs of progressive axonopathy are observed, related to progressive spastic paraplegia (SPG) associated with cognitive or behavioral disturbances. HLDs have been classified according to gene defects or associated signs. The X-linked HDL1 (PMD and SPG2) is related to the gene that controls the production of the major CNS myelin proteins, the proteolipid proteins (PLP). The gap junction protein, gamma 2 gene (GJC2) encoding oligodendrocyte-specific connexin, has been shown to be involved in the autosomal recessive HLD2 (PMLD1 and SPG44).

Boespflug-Tanguy O

2013-01-01

38

Myelin basic protein interacts with the myelin-specific ganglioside GM4.  

UK PubMed Central (United Kingdom)

Demyelinated plaques in multiple sclerosis have decreased amounts of both myelin basic protein and sialosylgalactosylceramide (GM4), a ganglioside specifically localized in myelin and oligodendroglia of the central nervous system. We have found that myelin basic protein is capable of releasing large quantities of entrapped [14C]glucose from multilamellar liposomes containing GM4. If the conformation of GM4 in liposomal membranes resembles that of GM4 in its natural environment, basic protein and GM4 may be associated within the myelin sheath of the central nervous system and their interaction altered in demyelinating diseases such as multiple sclerosis.

Mullin BR; Decandis FX; Montanaro AJ; Reid JD

1981-10-01

39

The quest for myelin in the adult brain.  

UK PubMed Central (United Kingdom)

Although myelination largely occurs during early postnatal life, myelinating oligodendrocytes are still generated in the adult brain. Myelin turnover in the adult is necessary for proper neuronal function and is gravely compromised in myelin disorders. The lineage relationship between adult neural stem cells and adult-born oligodendrocytes has been clarified, highlighting molecular pathways that could potentially be targeted to favour de novo myelination in pathological situations.

Zuccaro E; Arlotta P

2013-06-01

40

Nail Splitting (Onychoschizia)  

Science.gov (United States)

newsletter | contact Share | Nail Splitting (Onychoschizia) Information for adults A A A Onychoschizia means plate-like splitting of the free edge of the nail. Overview Onychoschizia, commonly known as nail splitting but ...

 
 
 
 
41

Gap junction communication in myelinating glia.  

UK PubMed Central (United Kingdom)

Gap junction communication is crucial for myelination and axonal survival in both the peripheral nervous system (PNS) and central nervous system (CNS). This review examines the different types of gap junctions in myelinating glia of the PNS and CNS (Schwann cells and oligodendrocytes respectively), including their functions and involvement in neurological disorders. Gap junctions mediate intercellular communication among Schwann cells in the PNS, and among oligodendrocytes and between oligodendrocytes and astrocytes in the CNS. Reflexive gap junctions mediating transfer between different regions of the same cell promote communication between cellular compartments of myelinating glia that are separated by layers of compact myelin. Gap junctions in myelinating glia regulate physiological processes such as cell growth, proliferation, calcium signaling, and participate in extracellular signaling via release of neurotransmitters from hemijunctions. In the CNS, gap junctions form a glial network between oligodendrocytes and astrocytes. This transcellular communication is hypothesized to maintain homeostasis by facilitating restoration of membrane potential after axonal activity via electrical coupling and the re-distribution of potassium ions released from axons. The generation of transgenic mice for different subsets of connexins has revealed the contribution of different connexins in gap junction formation and illuminated new subcellular mechanisms underlying demyelination and cognitive defects. Alterations in metabolic coupling have been reported in animal models of X-linked Charcot-Marie-Tooth disease (CMTX) and Pelizaeus-Merzbarcher-like disease (PMLD), which are caused by mutations in the genes encoding for connexin 32 and connexin 47 respectively. Future research identifying the expression and regulation of gap junctions in myelinating glia is likely to provide a better understanding of myelinating glia in nervous system function, plasticity, and disease. This article is part of a Special Issue entitled: The Communicating junctions, roles and dysfunctions.

Nualart-Marti A; Solsona C; Fields RD

2013-01-01

42

Myelin/oligodendrocyte glycoprotein (MOG) expression is associated with myelin deposition.  

UK PubMed Central (United Kingdom)

We investigated the onset of expression of the myelin/oligodendrocyte glycoprotein (MOG) mRNA and protein in the developing mouse central nervous system. In situ hybridization on brain sections at different stages of embryonic and postnatal development showed that MOG transcripts were first detected at birth in the medulla oblongata. During the first week after birth, cells expressing MOG mRNA were located in the ventral longitudinal funiculus. During the second postnatal week, the pattern of MOG mRNA expression extended rostrally to the mid-forebrain regions and reached completion by the beginning of the third week. MOG transcription was delayed by several days with respect to myelin basic protein (MBP), and it appeared that while the MBP probe labeled both non-myelinating and myelinating oligodendrocytes, only the latter were MOG-positive. In vitro, immunocytochemical analysis of MOG protein expression, performed on myelinating cultures derived from mouse brain embryos at 15 days of gestation, confirmed the strict restriction of MOG expression to myelinating oligodendrocytes. In particular, oligodendrocytes lining up their processes along axons, but not yet having started to deposit a myelin sheath, were still MOG negative. However, in the same cultures, pseudo-myelinating oligodendrocytes (i.e., cells not associated with neurites, but forming whorls of myelin-like figures) were MOG positive. Similarly, rat CG4 cells, an oligodendrocyte-like cell line, expressed MOG only after they had extended sheet-like processes, which suggested that the activation of MOG transcription depends more on an intrinsic oligodendroglial maturation program of myelination than on a neuronal signal.

Solly SK; Thomas JL; Monge M; Demerens C; Lubetzki C; Gardinier MV; Matthieu JM; Zalc B

1996-09-01

43

Myelin/oligodendrocyte glycoprotein (MOG) expression is associated with myelin deposition.  

Science.gov (United States)

We investigated the onset of expression of the myelin/oligodendrocyte glycoprotein (MOG) mRNA and protein in the developing mouse central nervous system. In situ hybridization on brain sections at different stages of embryonic and postnatal development showed that MOG transcripts were first detected at birth in the medulla oblongata. During the first week after birth, cells expressing MOG mRNA were located in the ventral longitudinal funiculus. During the second postnatal week, the pattern of MOG mRNA expression extended rostrally to the mid-forebrain regions and reached completion by the beginning of the third week. MOG transcription was delayed by several days with respect to myelin basic protein (MBP), and it appeared that while the MBP probe labeled both non-myelinating and myelinating oligodendrocytes, only the latter were MOG-positive. In vitro, immunocytochemical analysis of MOG protein expression, performed on myelinating cultures derived from mouse brain embryos at 15 days of gestation, confirmed the strict restriction of MOG expression to myelinating oligodendrocytes. In particular, oligodendrocytes lining up their processes along axons, but not yet having started to deposit a myelin sheath, were still MOG negative. However, in the same cultures, pseudo-myelinating oligodendrocytes (i.e., cells not associated with neurites, but forming whorls of myelin-like figures) were MOG positive. Similarly, rat CG4 cells, an oligodendrocyte-like cell line, expressed MOG only after they had extended sheet-like processes, which suggested that the activation of MOG transcription depends more on an intrinsic oligodendroglial maturation program of myelination than on a neuronal signal. PMID:8891690

Solly, S K; Thomas, J L; Monge, M; Demerens, C; Lubetzki, C; Gardinier, M V; Matthieu, J M; Zalc, B

1996-09-01

44

Involvement of Src in the membrane skeletal complex, MPP6-4.1G, in Schmidt-Lanterman incisures of mouse myelinated nerve fibers in PNS.  

Science.gov (United States)

Schmidt-Lanterman incisures (SLIs) are a specific feature of myelinated nerve fibers in the peripheral nervous system (PNS). In this study, we report localization of a signal transduction protein, Src, in the SLIs of mouse sciatic nerves, and its phosphorylation states in Y527 and Y418 (P527 and P418, respectively) under normal conditions or deletion of a membrane skeletal protein, 4.1G. In adult mouse sciatic nerves, Src was immunolocalized in SLIs as a cone-shape, as well as in paranodes and some areas of structures reminiscent of Cajal bands. By immunostaining in normal nerves, P527-Src was strongly detected in SLIs, whereas P418-Src was much weaker. Developmentally, P418-Src was detected in SLIs of early postnatal mouse sciatic nerves. The staining patterns for P527 and P418 in normal adult nerve fibers were opposite to those in primary culture Schwann cells and a Schwannoma cell line, RT4-D6P2T. In 4.1G-deficient nerve fibers, which had neither 4.1G nor the membrane protein palmitoylated 6 (MPP6) in SLIs, the P418-Src immunoreactivity in SLIs was clearly detected at a stronger level than that in the wild type. An immunoprecipitation study revealed Src interaction with MPP6. These findings indicate that the Src-MPP6-4.1G protein complex in SLIs has a role in signal transduction in the PNS. PMID:23306908

Terada, Nobuo; Saitoh, Yurika; Ohno, Nobuhiko; Komada, Masayuki; Yamauchi, Junji; Ohno, Shinichi

2013-01-10

45

Involvement of Src in the membrane skeletal complex, MPP6-4.1G, in Schmidt-Lanterman incisures of mouse myelinated nerve fibers in PNS.  

UK PubMed Central (United Kingdom)

Schmidt-Lanterman incisures (SLIs) are a specific feature of myelinated nerve fibers in the peripheral nervous system (PNS). In this study, we report localization of a signal transduction protein, Src, in the SLIs of mouse sciatic nerves, and its phosphorylation states in Y527 and Y418 (P527 and P418, respectively) under normal conditions or deletion of a membrane skeletal protein, 4.1G. In adult mouse sciatic nerves, Src was immunolocalized in SLIs as a cone-shape, as well as in paranodes and some areas of structures reminiscent of Cajal bands. By immunostaining in normal nerves, P527-Src was strongly detected in SLIs, whereas P418-Src was much weaker. Developmentally, P418-Src was detected in SLIs of early postnatal mouse sciatic nerves. The staining patterns for P527 and P418 in normal adult nerve fibers were opposite to those in primary culture Schwann cells and a Schwannoma cell line, RT4-D6P2T. In 4.1G-deficient nerve fibers, which had neither 4.1G nor the membrane protein palmitoylated 6 (MPP6) in SLIs, the P418-Src immunoreactivity in SLIs was clearly detected at a stronger level than that in the wild type. An immunoprecipitation study revealed Src interaction with MPP6. These findings indicate that the Src-MPP6-4.1G protein complex in SLIs has a role in signal transduction in the PNS.

Terada N; Saitoh Y; Ohno N; Komada M; Yamauchi J; Ohno S

2013-08-01

46

MMP-28 as a regulator of myelination  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Matrix metalloproteinase-28 (MMP-28) is a poorly understood member of the matrix metalloproteinase family. Metalloproteinases are important mediators in the development of the nervous system and can contribute to the maturation of the neural micro-environment. Results MMP-28 added to myelinating rat dorsal root ganglion (DRG) co-cultures reduces myelination and two antibodies targeted to MMP-28 (pAb180 and pAb183) are capable of binding MMP-28 and inhibiting its activity in a dose-dependent manner. Addition of 30 nM pAb180 or pAb183 to rat DRG cultures resulted in the 2.6 and 4.8 fold enhancement of myelination respectively while addition of MMP-28 to DRG co-cultures resulted in enhanced MAPK, ErbB2 and ErbB3 phosphorylation. MMP-28 protein expression was increased within demyelinated lesions of mouse experimental autoimmune encephalitis (EAE) and human multiple sclerosis lesions compared to surrounding normal tissue. Conclusion MMP-28 is upregulated in conditions of demyelination in vivo, induces signaling in vitro consistent with myelination inhibition and, neutralization of MMP-28 activity can enhance myelination in vitro. These results suggest inhibition of MMP-28 may be beneficial under conditions of dysmyelination.

Werner Sean R; Dotzlaf Joseph E; Smith Rosamund C

2008-01-01

47

Myelin-based inhibitors of oligodendrocyte myelination: clues from axonal growth and regeneration.  

UK PubMed Central (United Kingdom)

The differentiation of and myelination by oligodendrocytes (OLs) are exquisitely regulated by a series of intrinsic and extrinsic mechanisms. As each OL can make differing numbers of myelin segments with variable lengths along similar axon tracts, myelination can be viewed as a graded process shaped by inhibitory/inductive cues during development. Myelination by OLs is a prime example of an adaptive process determined by the microenvironment and architecture of the central nervous system (CNS). in this review, we discuss how myelin formation by OLs may be controlled by the heterogeneous microenvironment of the CNS. Then we address recent findings demonstrating that neighboring OLs may compete for available axon space, and highlight our current understanding of myelin-based inhibitors of axonal regeneration that are potentially responsible for the reciprocal dialogue between OLs and determine the numbers and lengths of myelin internodes. Understanding the mechanisms that control the spatiotemporal regulation of myelinogenic potential during development may provide valuable insight into therapeutic strategies for promoting remyelination in an inhibitory microenvironment.

Mei F; Christin Chong SY; Chan JR

2013-04-01

48

Impaired myelination of the human hippocampal formation in Down syndrome.  

UK PubMed Central (United Kingdom)

Myelination is considered as one of the last steps of neuronal development and is essential to the physiologically matured function of afferent and efferent pathways. In the present study, myelin formation was examined in the human fetal, postnatal and adult hippocampal formation in Down syndrome and in age-matched controls with immunohistochemistry detecting a protein component of the myelin sheath, the myelin basic protein synthesized by oligodendroglial cells. Myelination is mainly a postnatal event in the hippocampal formation of both healthy controls and in patients with Down syndrome. In patients with Down syndrome the sequence of myelination of the hippocampal formation followed a similar developmental pattern to that in controls. However, myelin formation was generally delayed in Down syndrome compared to age-matched controls. In addition, in the hilus of the dentate gyrus a decreased density of myelinated axons was detected from the start of myelination until adulthood. The majority of local axons (mossy fibers) are not myelinated in the hilar region and myelinated fibers arriving in the hilus come mainly from the subcortical septal nuclei. Since intact septo-hippocampal connections are necessary for memory formation, we hypothesize that decreased myelination in the hilus may contribute to the mental retardation of Down syndrome patients.

Ábrahám H; Vincze A; Veszprémi B; Kravják A; Gömöri É; Kovács GG; Seress L

2012-04-01

49

Impaired myelination of the human hippocampal formation in Down syndrome.  

Science.gov (United States)

Myelination is considered as one of the last steps of neuronal development and is essential to the physiologically matured function of afferent and efferent pathways. In the present study, myelin formation was examined in the human fetal, postnatal and adult hippocampal formation in Down syndrome and in age-matched controls with immunohistochemistry detecting a protein component of the myelin sheath, the myelin basic protein synthesized by oligodendroglial cells. Myelination is mainly a postnatal event in the hippocampal formation of both healthy controls and in patients with Down syndrome. In patients with Down syndrome the sequence of myelination of the hippocampal formation followed a similar developmental pattern to that in controls. However, myelin formation was generally delayed in Down syndrome compared to age-matched controls. In addition, in the hilus of the dentate gyrus a decreased density of myelinated axons was detected from the start of myelination until adulthood. The majority of local axons (mossy fibers) are not myelinated in the hilar region and myelinated fibers arriving in the hilus come mainly from the subcortical septal nuclei. Since intact septo-hippocampal connections are necessary for memory formation, we hypothesize that decreased myelination in the hilus may contribute to the mental retardation of Down syndrome patients. PMID:22155002

Ábrahám, Hajnalka; Vincze, András; Veszprémi, Béla; Kravják, András; Gömöri, Éva; Kovács, Gábor G; Seress, László

2011-12-06

50

Relevance of anti-myelin antibodies in Multiple Sclerosis  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Antibodies directed against myelin antigens have been described in multiple sclerosis (MS). Although anti-myelin antibodies have been implicated in central nervous system (CNS) demyelination, it is unclear to what extent anti-myelin antibodies contribute to MS pathogenesis. In this dissertation, ...

Breij, E.C.W.

51

Schwann cell myelination of the myelin deficient rat spinal cord following X-irradiation  

International Nuclear Information System (INIS)

The myelin-deficient (md) rat is an X-linked myelin mutant that has an abnormality of oligodendrocytes and a severe paucity of myelin throughout the CNS. This lack of myelin makes it an ideal model in which to study the cellular interactions that occur when foreign myelinating cells are induced in the milieu of this nonmyelinated CNS. In this study, Schwann cells were induced in the lumbosacral spinal cord by exposing it to radiation, a technique demonstrated repeatedly in other nonmutant strains of rats. Md rats and their age-matched littermates were irradiated (3,000 to 4,000 R) at 3 days of age and perfused 16-22 days later after pulse labeling with tritiated thymidine. In the md rat, Schwann cell invasion progressed from the area of the spinal cord-nerve root junction and extended into the dorsal columns and adjacent gray matter. Autoradiographic evidence revealed that many of these cells incorporated 3H-thymidine, indicating that they were undergoing proliferation. Ultrastructural observations showed that there was an integration of these intraspinal Schwann cells with the cells normally occurring in this environment, i.e., oligodendrocytes and astrocytes. The extent of migration and division of Schwann cells, as well as their interactions with glial cells, were similar to those seen in the nonmutant irradiated littermates. These studies provide conclusive evidence that md rat axons are normal with respect to their ability to provide trophic and mitogenic signals to myelinating cells.

1988-01-01

52

Autoantibodies against myelin antigens in patients with neuromyelitis optica  

Directory of Open Access Journals (Sweden)

Full Text Available In this study, we investigated the clinical relevance of anti-myelin antibodies in patients with neuromyelitis optica (NMO); titers of antibodies against myelin oligodendrocyte glycoproteins, proteolipid proteins and myelin basic proteins were measured in the sera of patients with NMO and compared to healthy controls, as well as to patients with other diseases. The frequency of presence of anti-myelin antibodies in patients with NMO was significantly higher than that in healthy and diseased controls. The expanded disability status scale scores correlated with the titers of the anti-myelin antibodies. Patients with anti-myelin antibody exhibited other autoantibodies significantly more frequently than patients without the antibody. Anti-myelin antibodies may be useful markers for predicting severe clinical courses in patients with NMO.

Kota Moriguchi; Katsuichi Miyamoto; Juri Ichihashi; Susumu Kusunoki

2013-01-01

53

Myelination in very low birth weight infants; Evaluation by MRI  

Energy Technology Data Exchange (ETDEWEB)

The prognostic significance of cerebral myelination was evaluated with magnetic resonance imaging (MRI) in very low birth weight infants. Myelination was graded in two specified sites, optic radiation and corpus callosum, based on the stages of normal term babies and healthy premature infants. The subjects were 30 preterm infants weighing less than 1,500 gm at birth. MRI was performed at 4 to 7 months (corrected age). The normal myelination stage was seen in 18 cases, while a delayed stage was noticed in 12 cases. In the normal myelination group, only 1 case (6%) had handicaps. In the delayed myelination group, 8 cases (67%) had handicaps. Our results showed that delayed myelination was closely related to a poor prognosis. We believe that MRI would be a very good imaging modality for predicting the outcome of very low birth weight infants, particularly in terms of evaluation of myelination. (author).

Noma, Kazuko; Tamai, Hiroshi; Shimada, Seiichi; Funato, Masahisa (Yodogawa Christian Hospital, Osaka (Japan))

1991-07-01

54

Thermocouple split follower  

Energy Technology Data Exchange (ETDEWEB)

Thermoelectric generator assembly accommodating differential thermal expansion between thermoelectric elements by means of a cylindrical split follower forming a slot and having internal spring loaded wedges that permit the split follower to open and close across the slot.

Howell, deceased, Louis J. (late of Upper Merion Township, Montgomery County, PA)

1980-01-01

55

Quantitative and integrative proteome analysis of peripheral nerve myelin identifies novel myelin proteins and candidate neuropathy loci.  

Science.gov (United States)

Peripheral nerve myelin facilitates rapid impulse conduction and normal motor and sensory functions. Many aspects of myelin biogenesis, glia-axonal interactions, and nerve homeostasis are poorly understood at the molecular level. We therefore hypothesized that only a fraction of all relevant myelin proteins has been identified so far. Combining gel-based and gel-free proteomic approaches, we identified 545 proteins in purified mouse sciatic nerve myelin, including 36 previously known myelin constituents. By mass spectrometric quantification, the predominant P0, periaxin, and myelin basic protein constitute 21, 16, and 8% of the total myelin protein, respectively, suggesting that their relative abundance was previously misestimated due to technical limitations regarding protein separation and visualization. Focusing on tetraspan-transmembrane proteins, we validated novel myelin constituents using immuno-based methods. Bioinformatic comparison with mRNA-abundance profiles allowed the categorization in functional groups coregulated during myelin biogenesis and maturation. By differential myelin proteome analysis, we found that the abundance of septin 9, the protein affected in hereditary neuralgic amyotrophy, is strongly increased in a novel mouse model of demyelinating neuropathy caused by the loss of prion protein. Finally, the systematic comparison of our compendium with the positions of human disease loci allowed us to identify several candidate genes for hereditary demyelinating neuropathies. These results illustrate how the integration of unbiased proteome, transcriptome, and genome data can contribute to a molecular dissection of the biogenesis, cell biology, metabolism, and pathology of myelin. PMID:22072688

Patzig, Julia; Jahn, Olaf; Tenzer, Stefan; Wichert, Sven P; de Monasterio-Schrader, Patricia; Rosfa, Susanne; Kuharev, Jörg; Yan, Kuo; Bormuth, Ingo; Bremer, Juliane; Aguzzi, Adriano; Orfaniotou, Foteini; Hesse, Dörte; Schwab, Markus H; Möbius, Wiebke; Nave, Klaus-Armin; Werner, Hauke Bernhard

2011-11-01

56

Necl-4/SynCAM-4 is expressed in myelinating oligodendrocytes but not required for axonal myelination.  

UK PubMed Central (United Kingdom)

The timing and progression of axonal myelination are precisely controlled by intercellular interactions between neurons and glia in development. Previous in vitro studies demonstrated that Nectin like 4 (Necl-4, also known as cell adhesion molecule Cadm-4 or SynCAM-4) plays an essential role in axonal myelination by Schwann cells in the peripheral nervous system (PNS). However, the role of Necl-4 protein in axonal myelination in the developing central nervous system (CNS) has remained unknown. In this study, we discovered upregulation of Necl-4 expression in mature oligodendrocytes at perinatal stages when axons undergo active myelination. We generated Necl4 gene knockout mice, but found that disruption of Necl-4 gene did not affect oligodendrocyte differentiation and myelin formation in the CNS. Surprisingly, disruption of Necl-4 had no significant effect on axonal myelination in the PNS either. Therefore, our results demonstrated that Necl-4 is dispensable for axonal myelination in the developing nervous system.

Zhu Y; Li H; Li K; Zhao X; An T; Hu X; Park J; Huang H; Bin Y; Qiang B; Yuan J; Peng X; Qiu M

2013-01-01

57

Necl-4/SynCAM-4 is expressed in myelinating oligodendrocytes but not required for axonal myelination.  

Science.gov (United States)

The timing and progression of axonal myelination are precisely controlled by intercellular interactions between neurons and glia in development. Previous in vitro studies demonstrated that Nectin like 4 (Necl-4, also known as cell adhesion molecule Cadm-4 or SynCAM-4) plays an essential role in axonal myelination by Schwann cells in the peripheral nervous system (PNS). However, the role of Necl-4 protein in axonal myelination in the developing central nervous system (CNS) has remained unknown. In this study, we discovered upregulation of Necl-4 expression in mature oligodendrocytes at perinatal stages when axons undergo active myelination. We generated Necl4 gene knockout mice, but found that disruption of Necl-4 gene did not affect oligodendrocyte differentiation and myelin formation in the CNS. Surprisingly, disruption of Necl-4 had no significant effect on axonal myelination in the PNS either. Therefore, our results demonstrated that Necl-4 is dispensable for axonal myelination in the developing nervous system. PMID:23700466

Zhu, Ying; Li, Hong; Li, Kehan; Zhao, Xiaofeng; An, Tai; Hu, Xuemei; Park, Jinsil; Huang, Hao; Bin, Yin; Qiang, Boqin; Yuan, Jiangang; Peng, Xiaozhong; Qiu, Mengsheng

2013-05-20

58

Generalised splitting of spacetime  

Science.gov (United States)

Normally, when a spacetime splitting is considered the ADM 3+1 split is brought to mind. In this paper, the idea of spacetime splitting is extended to include anm + n splitting of spacetime. The global spacetime has dimension (m + n) and the foliating spaces have dimensionm. There aren independent normals to each of these foliating spaces, thus givingn different extrinsic curvatures. The generalised Gauss-Weingarten and the generalised Gauss-Codazzi equations associated with this splitting are derived. These generalised equations reduce to the familar ADM equations when a 3+1 split is considered. The generalised equations are found to have a particularly elegant form when an orthogonal splitting of spacetime is examined.

McManus, Des J.

1992-06-01

59

The need for speed. II. Myelin in calanoid copepods.  

Science.gov (United States)

Speed of nerve impulse conduction is greatly increased by myelin, a multi-layered membranous sheath surrounding axons. Myelinated axons are ubiquitous among the vertebrates, but relatively rare among invertebrates. Electron microscopy of calanoid copepods using rapid cryofixation techniques revealed the widespread presence of myelinated axons. Myelin sheaths of up to 60 layers were found around both sensory and motor axons of the first antenna and interneurons of the ventral nerve cord. Except at nodes, individual lamellae appeared to be continuous and circular, without seams, as opposed to the spiral structure of vertebrate and annelid myelin. The highly organized myelin was characterized by the complete exclusion of cytoplasm from the intracellular spaces of the cell generating it. In regions of compaction, extracytoplasmic space was also eliminated. Focal or fenestration nodes, rather than circumferential ones, were locally common. Myelin lamellae terminated in stepwise fashion at these nodes, appearing to fuse with the axolemma or adjacent myelin lamellae. As with vertebrate myelin, copepod sheaths are designed to minimize both resistive and capacitive current flow through the internodal membrane, greatly speeding nerve impulse conduction. Copepod myelin differs from that of any other group described, while sharing features of every group. PMID:10798723

Weatherby, T M; Davis, A D; Hartline, D K; Lenz, P H

2000-04-01

60

Myelin inhibits oligodendroglial maturation and regulates oligodendrocytic transcription factor expression.  

UK PubMed Central (United Kingdom)

Myelin loss is a hallmark of multiple sclerosis (MS) and promoting central nervous system myelin repair has become a major therapeutic target. Despite the presence of oligodendrocytes precursors cells (OPCs) in chronic lesions of MS, remyelination often fails. The mechanism underlying this failure of remyelination remains unknown, but it is hypothesized that environmental cues act to inhibit the maturation/differentiation of oligodendroglia, preventing remyelination. The rate of CNS remyelination is correlated to the speed of phagocytosis of myelin debris, which is present following demyelination and trauma. Thus, myelin debris could inhibit CNS remyelination. Here, we demonstrate that OPCs cultured on myelin were robustly inhibited in their maturation, as characterized by the decreased expression of immature and mature oligodendrocytes markers, the impaired production of myelin gene products, as well as their stalled morphological complexity relative to OPCs cultured on a control substrate. OPCs in contact with myelin stopped proliferating and decreased the expression of OPC markers to a comparable degree as cells grown on a control substrate. The expression of two transcription factors known to prevent OPC differentiation and maturation were increased in cells that were in contact with myelin: inhibitor of differentiation family (ID) members 2 and 4. Overexpression of ID2 and ID4 in OPCs was previously reported to decrease the percentage of cells expressing mature oligodendrocyte markers. However, knockdown of ID2 and/or ID4 in OPCs did not increase oligodendroglial maturation on or off of myelin, suggesting that contact with myelin regulates additional regulatory elements.

Plemel JR; Manesh SB; Sparling JS; Tetzlaff W

2013-09-01

 
 
 
 
61

Myelin inhibits oligodendroglial maturation and regulates oligodendrocytic transcription factor expression.  

Science.gov (United States)

Myelin loss is a hallmark of multiple sclerosis (MS) and promoting central nervous system myelin repair has become a major therapeutic target. Despite the presence of oligodendrocytes precursors cells (OPCs) in chronic lesions of MS, remyelination often fails. The mechanism underlying this failure of remyelination remains unknown, but it is hypothesized that environmental cues act to inhibit the maturation/differentiation of oligodendroglia, preventing remyelination. The rate of CNS remyelination is correlated to the speed of phagocytosis of myelin debris, which is present following demyelination and trauma. Thus, myelin debris could inhibit CNS remyelination. Here, we demonstrate that OPCs cultured on myelin were robustly inhibited in their maturation, as characterized by the decreased expression of immature and mature oligodendrocytes markers, the impaired production of myelin gene products, as well as their stalled morphological complexity relative to OPCs cultured on a control substrate. OPCs in contact with myelin stopped proliferating and decreased the expression of OPC markers to a comparable degree as cells grown on a control substrate. The expression of two transcription factors known to prevent OPC differentiation and maturation were increased in cells that were in contact with myelin: inhibitor of differentiation family (ID) members 2 and 4. Overexpression of ID2 and ID4 in OPCs was previously reported to decrease the percentage of cells expressing mature oligodendrocyte markers. However, knockdown of ID2 and/or ID4 in OPCs did not increase oligodendroglial maturation on or off of myelin, suggesting that contact with myelin regulates additional regulatory elements. PMID:23839973

Plemel, Jason R; Manesh, Sohrab B; Sparling, Joseph S; Tetzlaff, Wolfram

2013-07-10

62

Tube splitting furnace  

International Nuclear Information System (INIS)

The application concerns a methane splitting plant, in which the heat produced in a nuclear reactor is directly used (i.e. without an intermediate circuit) in a process requiring heat, in order to split a CH4/H2O mixture by supplying heat and using a catalyst, into H2, CO and CO2. Coal can be gasified into methane with the hydrogen of the split gas obtained, or the split gas is used as a heat carrier in transporting the heat energy obtained in the high temperature reactor to a remove energy consumption location, where the split gas is again converted to methane by catalysis and the heat released is used. The methane splitting furnace is accommodated in the prestressed concrete pressure vessel with the high temperature reactor and the steam raising unit. The splitting furnace consists of three cylindrical spaces above one another, the primary circuit helium coming from the blower and flowing back to the high temperature reactor flows through the lowest space, which gives up its heat to the methane splitting tube projecting into it from above. Above this space there is the methane space, which has methane supplied to it from outside by a pipeline and which distributes it to the splitting tubes leading downwards. Each splitting tube contains a coaxial inner tube, in which the split gas produced is taken upwards to the top cylindrical space, from which the split gas is taken away by a pipeline. The design of the splitting furnace according to the invention, is simple and compact, requires little space and makes quick catalyst change and easy fitting and removal of the tube splitting furnace possible. (RB)

1976-04-06

63

Receptors for myelin inhibitors: Structures and therapeutic opportunities.  

UK PubMed Central (United Kingdom)

Many studies have indicated that the inability of adult mammalian central nervous system (CNS) to regenerate after injury is partly due to the existence of growth-inhibitory molecules associated with CNS myelin. Studies over the years have led to the identification of multiple myelin-associated inhibitors, among which Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (Omgp) represent potentially major contributors to CNS axon regeneration failure. Here we review in vitro and in vivo investigations into these inhibitory ligands and their functional mechanisms, focusing particularly on the neuronal receptors that mediate the inhibitory signals from these myelin molecules. A better understanding of the receptors for myelin-associated inhibitors could provide opportunities to decipher the mechanism of restriction in CNS regeneration, and lead to the development of potential therapeutic targets in neurodegenerative diseases and neurological injury. We will discuss the structures of the receptors and therapeutic opportunities that might arise based on this information.

Cao Z; Gao Y; Deng K; Williams G; Doherty P; Walsh FS

2010-01-01

64

Regional differences in myelination of chick vestibulocochlear ganglion cells.  

UK PubMed Central (United Kingdom)

In vertebrates, vestibular and cochlear ganglion (VG and CG, respectively) cells are bipolar neurons with myelinated axons and perikarya. The time course of the myelination of the VG and CG cells during development of chick embryos was investigated. Chick VG and CG from embryonic day at 7-20 (E7-20) were prepared for a transmission electron microscopy, myelin basic protein immunohistochemistry, and real-time quantitative RT-PCR. In the VG cells, myelination was first observed on the peripheral axons of the ampullar nerves at E10, on the utricular and saccular nerves at E12, and on the lagenar and neglecta nerves at E13. In the VG central axons, myelination was first seen on the ampullar nerves at E11, on the utricular and saccular nerves at E13, and on the lagenar nerves at E13. In the CG cells, the myelination was first observed on the peripheral and central axons at E14. In both VG and CG, myelination was observed on the perikarya at E17. These results suggest that the onset of the axonal myelination on the VG cells occurred earlier than that on the CG cells, whereas the perikaryal myelination occurred at about the same time on the both types of ganglion cells. Moreover, the myelination on the ampullar nerves occurred earlier than that on the utricular and saccular nerves. The myelination on the peripheral axons occurred earlier than that on the central axons of the VG cells, whereas that on the central and peripheral axons of the CG cells occurred at about the same time. The regional differences in myelination in relation to the onset of functional activities in the VG and CG cells are discussed.

Sun YJ; Kobayashi H; Yoshida S; Shirasawa N; Naito A

2013-07-01

65

Unconjugated bilirubin restricts oligodendrocyte differentiation and axonal myelination.  

UK PubMed Central (United Kingdom)

High levels of serum unconjugated bilirubin (UCB) in newborns are associated with axonal damage and glial reactivity that may contribute to subsequent neurologic injury and encephalopathy (kernicterus). Impairments in myelination and white matter damage were observed at autopsy in kernicteric infants. We have recently reported that UCB reduces oligodendrocyte progenitor cell (OPC) survival in a pure OPC in vitro proliferative culture. Here, we hypothesized that neonatal hyperbilirubinemia may also impair oligodendrocyte (OL) maturation and myelination. We used an experimental model of hyperbilirubinemia that has been shown to mimic the pathophysiological conditions leading to brain dysfunction by unbound (free) UCB. Using primary cultures of OL, we demonstrated that UCB delays cell differentiation by increasing the OPC number and reducing the number of mature OL. This finding was combined with a downregulation of Olig1 mRNA levels and upregulation of Olig2 mRNA levels. Addition of UCB, prior to or during differentiation, impaired OL morphological maturation, extension of processes and cell diameter. Both conditions reduced active guanosine triphosphate (GTP)-bound Rac1 fraction. In myelinating co-cultures of dorsal root ganglia neurons and OL, UCB treatment prior to the onset of myelination decreased oligodendroglial differentiation and the number of myelinating OL, also observed when UCB was added after the onset of myelination. In both circumstances, UCB decreased the number of myelin internodes per OL, as well as the myelin internode length. Our studies demonstrate that increased concentrations of UCB compromise myelinogenesis, thereby elucidating a potential deleterious consequence of elevated UCB.

Barateiro A; Miron VE; Santos SD; Relvas JB; Fernandes A; Ffrench-Constant C; Brites D

2013-04-01

66

Unconjugated bilirubin restricts oligodendrocyte differentiation and axonal myelination.  

Science.gov (United States)

High levels of serum unconjugated bilirubin (UCB) in newborns are associated with axonal damage and glial reactivity that may contribute to subsequent neurologic injury and encephalopathy (kernicterus). Impairments in myelination and white matter damage were observed at autopsy in kernicteric infants. We have recently reported that UCB reduces oligodendrocyte progenitor cell (OPC) survival in a pure OPC in vitro proliferative culture. Here, we hypothesized that neonatal hyperbilirubinemia may also impair oligodendrocyte (OL) maturation and myelination. We used an experimental model of hyperbilirubinemia that has been shown to mimic the pathophysiological conditions leading to brain dysfunction by unbound (free) UCB. Using primary cultures of OL, we demonstrated that UCB delays cell differentiation by increasing the OPC number and reducing the number of mature OL. This finding was combined with a downregulation of Olig1 mRNA levels and upregulation of Olig2 mRNA levels. Addition of UCB, prior to or during differentiation, impaired OL morphological maturation, extension of processes and cell diameter. Both conditions reduced active guanosine triphosphate (GTP)-bound Rac1 fraction. In myelinating co-cultures of dorsal root ganglia neurons and OL, UCB treatment prior to the onset of myelination decreased oligodendroglial differentiation and the number of myelinating OL, also observed when UCB was added after the onset of myelination. In both circumstances, UCB decreased the number of myelin internodes per OL, as well as the myelin internode length. Our studies demonstrate that increased concentrations of UCB compromise myelinogenesis, thereby elucidating a potential deleterious consequence of elevated UCB. PMID:23086523

Barateiro, Andreia; Miron, Veronique E; Santos, Sofia D; Relvas, Joăo B; Fernandes, Adelaide; Ffrench-Constant, Charles; Brites, Dora

2012-10-21

67

Myelin-phagocytosing macrophages modulate autoreactive T cell proliferation  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Introduction Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) in which macrophages play a central role. Initially, macrophages where thought to be merely detrimental in MS, however, recent evidence suggests that their functional phenotype is altered following myelin phagocytosis. Macrophages that have phagocytosed myelin may be less inflammatory and may exert beneficial effects. The presence of myelin-containing macrophages in CNS-draining lymph nodes and perivascular spaces of MS patients suggests that these cells are ideally positioned to exert an immune regulatory role. Therefore we evaluated in this study the effect of myelin-phagocytosing macrophages on lymphocyte reactivity. Methods Thioglycolate-elicited rat peritoneal macrophages were loaded with myelin and cocultured with myelin-basic protein (MBP) or ovalbumin (OVA) reactive lymphocytes. Lymphocyte proliferation was determined by CFSE-labeling. The role of nitric oxide in regulating lymphocyte proliferation was assessed by addition of an inhibitor of inducible nitric oxide synthase to the coculture. In vivo immune regulation was investigated by treating MBP- and OVA-immunized animals subcutaneously with myelin. Cognate antigen specific lymphocyte proliferation and nitric oxide production were determined 9d post-immunization. Results In this study we demonstrate that myelin-phagocytosing macrophages inhibit TCR-triggered lymphocyte proliferation in an antigen-independent manner. The observed immune suppression is mediated by an increase in NO production by myelin-phagocytosing macrophages upon contact with lymphocytes. Additionally, myelin delivery to primarily CD169+ macrophages in popliteal lymph nodes of OVA-immunized animals results in a reduced cognate antigen specific proliferation. In contrast to OVA-immunized animals, lymphocytes from MBP-immunized animals displayed an increased proliferation after stimulation with their cognate antigen, indicating that myelin-phagocytosing macrophages have dual effects depending on the specificity of surrounding lymphocytes. Conclusions Collectively our data show that myelin phagocytosis leads to an altered macrophage function that inhibits lymphocyte proliferation. Additionally, results from this study indicate that myelin-phagocytosing macrophages fulfill a dual role in vivo. On one hand they aggravate autoimmunity by activating myelin-reactive lymphocytes and on the other hand they suppress lymphocyte reactivity by producing NO.

Bogie Jeroen FJ; Stinissen Piet; Hellings Niels; Hendriks Jerome JA

2011-01-01

68

Evaluating dermal myelinated nerve fibers in skin biopsy.  

UK PubMed Central (United Kingdom)

Although there has been extensive research on small, unmyelinated fibers in the skin, little research has investigated dermal myelinated fibers in comparison. Glabrous, nonhairy skin contains mechanoreceptors that afford a vantage point for observation of myelinated fibers that have previously been seen only with invasively obtained nerve biopsies. This review discusses current morphometric and molecular expression data of normative and pathogenic glabrous skin obtained by various processing and analysis methods for cutaneous myelinated fibers. Recent publications have shed light on the role of glabrous skin biopsy in identifying signs of peripheral neuropathy and as a potential biomarker of distal myelin and mechanoreceptor integrity. The clinical relevance of a better understanding of the role of dermal myelinated nerve terminations in peripheral neuropathy will be addressed in light of recent publications in the growing field of skin biopsy.

Myers MI; Peltier AC; Li J

2013-01-01

69

Evaluation of dermal myelinated nerve fibers in diabetes mellitus.  

UK PubMed Central (United Kingdom)

Skin biopsies have primarily been used to study the non-myelinated nerve fibers of the epidermis in a variety of neuropathies. In this study, we have expanded the skin biopsy technique to glabrous, non-hairy skin to evaluate myelinated nerve fibers in the most highly prevalent peripheral nerve disease, diabetic polyneuropathy (DPN). Twenty patients with DPN (Type I, n = 9; Type II, n = 11) and 16 age-matched healthy controls (age 29-73) underwent skin biopsy of the index finger, nerve conduction studies (NCS), and composite neuropathy scoring. In patients with DPN, we found a statistically significant reduction of both mechanoreceptive Meissner corpuscles (MCs) and their afferent myelinated nerve fibers (p = 0.01). This myelinated nerve fiber loss was correlated with the decreased amplitudes of sensory/motor responses in NCS. This study supports the utilization of skin biopsy to quantitatively evaluate axonal loss of myelinated nerve fibers in patients with DPN.

Peltier AC; Myers MI; Artibee KJ; Hamilton AD; Yan Q; Guo J; Shi Y; Wang L; Li J

2013-06-01

70

Myelin gene regulatory factor is required for maintenance of myelin and mature oligodendrocyte identity in the adult CNS.  

UK PubMed Central (United Kingdom)

Although the transcription factors required for the generation of oligodendrocytes and CNS myelination during development have been relatively well established, it is not known whether continued expression of the same factors is required for the maintenance of myelin in the adult. Here, we use an inducible conditional knock-out strategy to investigate whether continued oligodendrocyte expression of the recently identified transcription factor myelin gene regulatory factor (MRF) is required to maintain the integrity of myelin in the adult CNS. Genetic ablation of MRF in mature oligodendrocytes within the adult CNS resulted in a delayed but severe CNS demyelination, with clinical symptoms beginning at 5 weeks and peaking at 8 weeks after ablation of MRF. This demyelination was accompanied by microglial/macrophage infiltration and axonal damage. Transcripts for myelin genes, such as proteolipid protein, MAG, MBP, and myelin oligodendrocyte glycoprotein, were rapidly downregulated after ablation of MRF, indicating an ongoing requirement for MRF in the expression of these genes. Subsequently, a proportion of the recombined oligodendrocytes undergo apoptosis over a period of weeks. Surviving oligodendrocytes gradually lose the expression of mature markers such as CC1 antigen and their association with myelin, without reexpressing oligodendrocyte progenitor markers or reentering the cell cycle. These results demonstrate that ongoing expression of MRF within the adult CNS is critical to maintain mature oligodendrocyte identity and the integrity of CNS myelin.

Koenning M; Jackson S; Hay CM; Faux C; Kilpatrick TJ; Willingham M; Emery B

2012-09-01

71

Induction of experimental autoimmune encephalomyelitis in guinea pigs using myelin basic protein and myelin glycolipids.  

UK PubMed Central (United Kingdom)

Strain 13 guinea pigs were immunized with galactocerebroside, asialo-GM1 (GA1) or GM4 ganglioside in association with myelin basic protein (MBP) in complete Freund's adjuvant (CFA) to produce experimental autoimmune encephalomyelitis (EAE). The clinical and pathological features, serum antibodies, and lipid compositions of affected brains and spinal cords were compared with those of guinea pigs immunized with MBP, in CFA, alone. Perivascular demyelination was seen in brains from all guinea pigs immunized with GA1/MBP. The incidence and degree of demyelination in this group were significantly higher than in the group immunized with only MBP. The onset of EAE was slightly, but significantly, retarded in groups of animals immunized with GM4/MBP and there was no detectable demyelination. Otherwise, no significant differences were detected between groups. Augmentation of EAE by myelin glycolipids may provide some important clues in understanding the mechanism of demyelinating diseases.

Kusunoki S; Yu RK; Kim JH

1988-07-01

72

Evaluation of myelination and myelination disorders with turbo inversion recovery magnetic resonance imaging  

International Nuclear Information System (INIS)

The aim of our work was to determine the efficacy of turbo inversion recovery spin echo (TIRSE) pulse sequences in differentiating patients with normal and abnormal myelination. Twenty neurological normal children (aged 5 months to 12 years) as well as 65 children presenting clinically with neurologic developmental deficits (aged 2 months to 10 years) were examined using TIRSE, T1-weighted SE, and T2-weighted turbo SE pulse sequences. Contrast-to-noise-ratio (CNR) between myelinated white and gray matter was compared for the different pulse sequences. In addition, two readers analyzed all images qualitatively by consensus. The CNR values were significantly higher on TIRSE images as compared with conventional images (p

1997-01-01

73

Instantons and splitting  

Energy Technology Data Exchange (ETDEWEB)

In this paper we compare various formulas for the leading term of the amplitude of the splitting of the eigenvalues of semiclassical Schr{umlt o}dinger operators with multiple wells. {copyright} {ital 1997 American Institute of Physics.}

Sordoni, V. [Dipartimento di Matematica, Universita di Bologna, Piazza di Porta S. Donato, 5, 40127 Bologna (Italy)

1997-02-01

74

CSF myelin basic protein in multiple sclerosis.  

UK PubMed Central (United Kingdom)

Cerebrospinal fluid (CSF) from 221 patients with multiple sclerosis (MS) and 85 patients with other neurological disorders (OND) was examined using a competitive radioimmunoassay for myelin basic protein (MBP) immunoreactivity. MBP was found in 46 of 55 MS patients (84%) examined within six weeks of relapse but in only 11 of 85 patients (13%) with OND. There was a significant correlation between the concentration of MBP in the CSF and relapse severity in patients seen within four weeks of the onset of symptoms (p less than 0.01). Of 44 patients in remission, MBP was detected in 12, and these patients had a significantly higher tendency to subsequent relapse (p less than 0.05). In 72 patients with progressive disease the presence of MBP in the CSF reflected the confidence of clinical diagnosis. The results of this study suggest that measurement of MBP in the CSF gives an objective method of monitoring disease activity in patient with MS.

Thomson AJ; Brazil J; Feighery C; Whelan A; Kellet J; Martin EA; Hutchinson M

1985-12-01

75

CSF myelin basic protein in multiple sclerosis.  

Science.gov (United States)

Cerebrospinal fluid (CSF) from 221 patients with multiple sclerosis (MS) and 85 patients with other neurological disorders (OND) was examined using a competitive radioimmunoassay for myelin basic protein (MBP) immunoreactivity. MBP was found in 46 of 55 MS patients (84%) examined within six weeks of relapse but in only 11 of 85 patients (13%) with OND. There was a significant correlation between the concentration of MBP in the CSF and relapse severity in patients seen within four weeks of the onset of symptoms (p less than 0.01). Of 44 patients in remission, MBP was detected in 12, and these patients had a significantly higher tendency to subsequent relapse (p less than 0.05). In 72 patients with progressive disease the presence of MBP in the CSF reflected the confidence of clinical diagnosis. The results of this study suggest that measurement of MBP in the CSF gives an objective method of monitoring disease activity in patient with MS. PMID:2420146

Thomson, A J; Brazil, J; Feighery, C; Whelan, A; Kellet, J; Martin, E A; Hutchinson, M

1985-12-01

76

Stimulation of adult oligodendrogenesis by myelin-specific T cells  

DEFF Research Database (Denmark)

In multiple sclerosis (MS), myelin-specific T cells are normally associated with destruction of myelin and axonal damage. However, in acute MS plaque, remyelination occurs concurrent with T-cell infiltration, which raises the question of whether T cells might stimulate myelin repair. We investigated the effect of myelin-specific T cells on oligodendrocyte formation at sites of axonal damage in the mouse hippocampal dentate gyrus. Infiltrating T cells specific for myelin proteolipid protein stimulated proliferation of chondroitin sulfate NG2-expressing oligodendrocyte precursor cells early after induction via axonal transection, resulting in a 25% increase in the numbers of oligodendrocytes. In contrast, T cells specific for ovalbumin did not stimulate the formation of new oligodendrocytes. In addition, infiltration of myelin-specific T cells enhanced the sprouting response of calretinergic associational/commissural fibers within the dentate gyrus. These results have implications for the perception of MS pathogenesis because they show that infiltrating myelin-specific T cells can stimulate oligodendrogenesis in the adult central nervous system.

Hvilsted Nielsen, Helle; Toft-Hansen, Henrik

2011-01-01

77

A role for nociceptive, myelinated nerve fibers in itch sensation.  

Science.gov (United States)

Despite its clinical importance, the underlying neural mechanisms of itch sensation are poorly understood. In many diseases, pruritus is not effectively treated with antihistamines, indicating the involvement of nonhistaminergic mechanisms. To investigate the role of small myelinated afferents in nonhistaminergic itch, we tested, in psychophysical studies in humans, the effect of a differential nerve block on itch produced by intradermal insertion of spicules from the pods of a cowhage plant (Mucuna pruriens). Electrophysiological experiments in anesthetized monkey were used to investigate the responsiveness of cutaneous, nociceptive, myelinated afferents to different chemical stimuli (cowhage spicules, histamine, capsaicin). Our results provide several lines of evidence for an important role of myelinated fibers in cowhage-induced itch: (1) a selective conduction block in myelinated fibers substantially reduces itch in a subgroup of subjects with A-fiber-dominated itch, (2) the time course of itch sensation differs between subjects with A-fiber- versus C-fiber-dominated itch, (3) cowhage activates a subpopulation of myelinated and unmyelinated afferents in monkey, (4) the time course of the response to cowhage is different in myelinated and unmyelinated fibers, (5) the time of peak itch sensation for subjects with A-fiber-dominated itch matches the time for peak response in myelinated fibers, and (6) the time for peak itch sensation for subjects with C-fiber-dominated itch matches the time for the peak response in unmyelinated fibers. These findings demonstrate that activity in nociceptive, myelinated afferents contributes to cowhage-induced sensations, and that nonhistaminergic itch is mediated through activity in both unmyelinated and myelinated afferents. PMID:22016517

Ringkamp, Matthias; Schepers, Raf J; Shimada, Steven G; Johanek, Lisa M; Hartke, Timothy V; Borzan, Jasenka; Shim, Beom; LaMotte, Robert H; Meyer, Richard A

2011-10-19

78

A role for nociceptive, myelinated nerve fibers in itch sensation.  

UK PubMed Central (United Kingdom)

Despite its clinical importance, the underlying neural mechanisms of itch sensation are poorly understood. In many diseases, pruritus is not effectively treated with antihistamines, indicating the involvement of nonhistaminergic mechanisms. To investigate the role of small myelinated afferents in nonhistaminergic itch, we tested, in psychophysical studies in humans, the effect of a differential nerve block on itch produced by intradermal insertion of spicules from the pods of a cowhage plant (Mucuna pruriens). Electrophysiological experiments in anesthetized monkey were used to investigate the responsiveness of cutaneous, nociceptive, myelinated afferents to different chemical stimuli (cowhage spicules, histamine, capsaicin). Our results provide several lines of evidence for an important role of myelinated fibers in cowhage-induced itch: (1) a selective conduction block in myelinated fibers substantially reduces itch in a subgroup of subjects with A-fiber-dominated itch, (2) the time course of itch sensation differs between subjects with A-fiber- versus C-fiber-dominated itch, (3) cowhage activates a subpopulation of myelinated and unmyelinated afferents in monkey, (4) the time course of the response to cowhage is different in myelinated and unmyelinated fibers, (5) the time of peak itch sensation for subjects with A-fiber-dominated itch matches the time for peak response in myelinated fibers, and (6) the time for peak itch sensation for subjects with C-fiber-dominated itch matches the time for the peak response in unmyelinated fibers. These findings demonstrate that activity in nociceptive, myelinated afferents contributes to cowhage-induced sensations, and that nonhistaminergic itch is mediated through activity in both unmyelinated and myelinated afferents.

Ringkamp M; Schepers RJ; Shimada SG; Johanek LM; Hartke TV; Borzan J; Shim B; LaMotte RH; Meyer RA

2011-10-01

79

Split Special Lagrangian Geometry  

CERN Multimedia

One purpose of this article is to draw attention to the seminal work of J. Mealy in 1989 on calibrations in semi-riemannian geometry where split SLAG geometry was first introduced. The natural setting is provided by doing geometry with the complex numbers C replaced by the double numbers D, where i with i^2 = -1 is replaced by tau with tau^2 = 1. A rather surprising amount of complex geometry carries over, almost untouched, and this has been the subject of many papers. We briefly review this material and, in particular, we discuss Hermitian D-manifolds with trivial canonical bundle, which provide the background space for the geometry of split SLAG submanifolds. A removable singularities result is proved for split SLAG subvarieties. It implies, in particular, that there exist no split SLAG cones, smooth outside the origin, other than planes. This is in sharp contrast to the complex case. Parallel to the complex case, space-like Lagrangian submanifolds are stationary if and only if they are theta-split SLAG for...

Harvey, F Reese

2010-01-01

80

[Binding of delta-aminolevulinic acid by myelin proteins  

UK PubMed Central (United Kingdom)

Delta-[14C]aminolevulinic acid (ALA) was injected intracranially into experimental animals; the gray and white matter was obtained from the brain 24 hours thereafter. The radioactive label content in the ALA, protoporphyrin, microsomes, mitochondria, cell membranes and myelin was determined; no radioactivity was detected in ALA and protoporphyrin. The radioactive label was localized in the subcellular fractions and myelin, in particular, in the white matter. Analysis of protein myelin fractions demonstrated that ALA was incorporated into practically all basic proteins. The highest capacity to bind ALA was observed in case of Wolfgram proteins; however, almost half of the bound ALA in the myelin fraction was found within the composition of basic proteins. It was assumed that the binding of ALA to proteins occurs via the amide, carboxylic and keto groups of ALA.

Muzyka VI; Moks MA

1984-10-01

 
 
 
 
81

Oligodendrocyte differentiation and myelination defects in OMgp null mice.  

UK PubMed Central (United Kingdom)

OMgp is selectively expressed in CNS by oligodendrocyte. However, its potential role(s) in oligodendrocyte development and myelination remain unclear. We show that OMgp null mice are hypomyelinated in their spinal cords, resulting in slower ascending and descending conduction velocities compared to wild-type mice. Consistent with the hypomyelination, in the MOG induced EAE model, OMgp null mice show a more severe EAE clinical disease and slower nerve conduction velocity compared to WT animals. The contribution of OMgp to oligodendrocyte differentiation and myelination was verified using cultured oligodendrocytes from null mice. Oligodendrocytes isolated from OMgp null mice show a significant decrease in the number of MBP(+) cells and in myelination compared to wild-type mice. The dramatic effects of the OMgp KO in oligodendrocyte maturation in vivo and in vitro reveal a new and important function for OMgp in regulating CNS myelination.

Lee X; Hu Y; Zhang Y; Yang Z; Shao Z; Qiu M; Pepinsky B; Miller RH; Mi S

2011-04-01

82

Random Heegaard splittings  

CERN Multimedia

A random Heegaard splitting is a 3-manifold obtained by using a random walk of length n on the mapping class group as the gluing map between two handlebodies. We show that the joint distribution of random walks of length n and their inverses is asymptotically independent, and converges to the product of the harmonic and reflected harmonic measures defined by the random walk. We use this to show that the translation length on the curve complex of a random walk grows linearly in the length of the walk, and similarly, that distance in the curve complex between the disc sets of a random Heegaard splitting grows linearly in n. In particular, this implies that a random Heegaard splitting is hyperbolic with asymptotic probability one.

Maher, Joseph

2008-01-01

83

Gangliosides and proteins in developing chicken brain myelin.  

UK PubMed Central (United Kingdom)

Ganglioside and protein content of chicken brain myelin have been studied as a function of development and maturation. Ganglioside concentration remained relatively constant at approximately 225-266 micrograms sialic acid per 100 mg myelin, from 17-day-old embryos to 540-day-old adults. The ganglioside distributional pattern was also constant, GM1 and GM4 each accounting for approximately one-third of total sialic acid. These properties are contrasted with those of mouse and rat brain myelin which previously showed enrichment of GM1 at early stages of myelination and appearance of GM4 at a later stage of maturation. In an earlier study of the mouse total myelin gangliosides doubled in concentration between 3 and 5 weeks of age and full maturity. Myelin proteins of the chicken also remained relatively constant in concentration and distributional pattern during development, although the percentage of basic protein increased somewhat during the first few weeks after hatching. Correlations were observed between molar concentrations of basic protein and various gangliosides, particularly the monosialo types.

Cochran FB; Ledeen RW; Yu RK

1982-12-01

84

Myelin Recovery in Multiple Sclerosis: The Challenge of Remyelination  

Directory of Open Access Journals (Sweden)

Full Text Available Multiple sclerosis (MS) is the most common demyelinating and an autoimmune disease of the central nervous system characterized by immune-mediated myelin and axonal damage, and chronic axonal loss attributable to the absence of myelin sheaths. T cell subsets (Th1, Th2, Th17, CD8+, NKT, CD4+CD25+ T regulatory cells) and B cells are involved in this disorder, thus new MS therapies seek damage prevention by resetting multiple components of the immune system. The currently approved therapies are immunoregulatory and reduce the number and rate of lesion formation but are only partially effective. This review summarizes current understanding of the processes at issue: myelination, demyelination and remyelination—with emphasis upon myelin composition/ architecture and oligodendrocyte maturation and differentiation. The translational options target oligodendrocyte protection and myelin repair in animal models and assess their relevance in human. Remyelination may be enhanced by signals that promote myelin formation and repair. The crucial question of why remyelination fails is approached is several ways by examining the role in remyelination of available MS medications and avenues being actively pursued to promote remyelination including: (i) cytokine-based immune-intervention (targeting calpain inhibition), (ii) antigen-based immunomodulation (targeting glycolipid-reactive iNKT cells and sphingoid mediated inflammation) and (iii) recombinant monoclonal antibodies-induced remyelination.

Maria Podbielska; Naren L. Banik; Ewa Kurowska; Edward L. Hogan

2013-01-01

85

Split image optical display  

Energy Technology Data Exchange (ETDEWEB)

A video image is displayed from an optical panel by splitting the image into a plurality of image components, and then projecting the image components through corresponding portions of the panel to collectively form the image. Depth of the display is correspondingly reduced.

Veligdan, James T. (Manorville, NY)

2007-05-29

86

Muscle-splitting thoracotomy.  

Science.gov (United States)

Muscle-splitting thoracotomy avoids transection of the latissimus dorsi and the serratus anterior muscles, thereby decreasing post thoracotomy pain and preserving the function and viability of these two muscles. The exposure provided for most intrathoracic procedures is excellent. PMID:9544153

Sadighi, P J; Woodworth, C S

1998-04-01

87

Stabilization of Heegaard splittings  

CERN Document Server

For each g greater than one there is a 3-manifold with two genus g Heegaard splittings that require g stabilizations to become equivalent. Previously known examples required at most one stabilization. Control of families of Heegaard surfaces is obtained through a deformation to harmonic maps.

Hass, Joel; Thurston, William

2008-01-01

88

Epigenetic Modifiers Are Necessary but Not Sufficient for Reprogramming Non-Myelinating Cells into Myelin Gene-Expressing Cells  

Science.gov (United States)

Background Modifications on specific histone residues and DNA methylation play an essential role in lineage choice and cellular reprogramming. We have previously shown that histone modifications or combinatorial codes of transcription factors (TFs) are critical for the differentiation of multipotential progenitors into myelinating oligodendrocytes. In this study we asked whether combining global manipulation of DNA methylation and histone acetylation together with the expression of oligodendrocyte- specific TFs, was sufficient to switch the identity of fibroblasts into myelin gene-expressing cells. Methodology/Principal Findings Transfection of six oligodendrocyte-specific TFs (Olig1, Olig2, Sox10, Mash1, E47 and Nkx2.2) into NIH3T3 fibroblasts was capable of inducing expression of myelin gene promoter-driven reporters, but did not activate endogenous myelin gene expression. These results suggested the existence of a transcriptionally incompetent chromatin conformation in NIH3T3 fibroblasts. Using chromatin immunoprecipitation (ChIP) analysis, we compared the histone code on the conserved regions of myelin genes (i.e. Mbp and Mag) in differentiating oligodendrocyte progenitors and NIH3T3 fibroblasts. Chromatin at myelin gene loci was characterized by the presence of repressive histone modifications (me3K9H3 and me3K27H3) in NIH3T3 fibroblasts and active histone marks (me3K4H3 and AcH3) in oligodendrocyte lineage cells. To induce a transcriptionally competent chromatin signature, NIH3T3 fibroblasts were treated with 5-azadeoxy-citidine (5-AzaC) to decrease DNA methylation, and trichostatin A (TSA) or sirtinol, to favor histone acetylation. Treatment with 5-AzaC/TSA but not sirtinol, resulted in the detection of endogenous myelin gene transcripts in fibroblasts, although not to the levels detected in myelinating cells. Transfection of oligodendrocyte-specific TFs after 5-AzaC/TSA treatment did not further increase myelin gene expression, nor did it reprogram the transcriptional network of NIH3T3 fibroblasts into that of oligodendrocytes. Conclusions/Significance These results suggest that reprogramming of fibroblasts into myelin gene-expressing cells not only requires transcriptional activation, but also chromatin manipulations that go beyond histone acetylation and DNA methylation.

Liu, Jia; Sandoval, Juan; Doh, Sung Tae; Cai, Li; Lopez-Rodas, Gerardo; Casaccia, Patrizia

2010-01-01

89

Classical splitting of fundamental strings  

CERN Multimedia

We find exact solutions of the string equations of motion and constraints describing the {\\em classical}\\ splitting of a string into two. We show that for the same Cauchy data, the strings that split have {\\bf smaller} action than the string without splitting. This phenomenon is already present in flat space-time. The mass, energy and momentum carried out by the strings are computed. We show that the splitting solution describes a natural decay process of one string of mass M into two strings with a smaller total mass and some kinetic energy. The standard non-splitting solution is contained as a particular case. We also describe the splitting of a closed string in the background of a singular gravitational plane wave, and show how the presence of the strong gravitational field increases (and amplifies by an overall factor) the negative difference between the action of the splitting and non-splitting solutions.

De Vega, H J; Ramón-Medrano, M; Sánchez, N; de Vega, H J; Ram, J; Medrano, M Ramon; Sanchez, N

1998-01-01

90

Heegaard splittings of graph manifolds  

CERN Multimedia

Let M be a totally orientable graph manifold with characteristic submanifold T and let M = V cup_S W be a Heegaard splitting. We prove that S is standard. In particular, S is the amalgamation of strongly irreducible Heegaard splittings. The splitting surfaces S_i of these strongly irreducible Heegaard splittings have the property that for each vertex manifold N of M, S_i cap N is either horizontal, pseudohorizontal, vertical or pseudovertical.

Schultens, J

2004-01-01

91

Surface bundles versus Heegaard splittings  

CERN Multimedia

This paper studies Heegaard splittings of surface bundles via the curve complex of the fibre. The translation distance of the monodromy is the smallest distance it moves any vertex of the curve complex. We prove that the translation distance is bounded above in terms of the genus of any strongly irreducible Heegaard splitting. As a consequence, if a splitting surface has small genus compared to the translation distance of the monodromy, the splitting is standard.

Bachman, D C; Bachman, David; Schleimer, Saul

2002-01-01

92

In vivo acylation of proteolipid protein and DM-20 in myelin and myelin subfractions of developing rat brain: immunoblot identification of acylated PLP and DM-20  

International Nuclear Information System (INIS)

[en] The acylation of proteolipid protein (PLP) was examined in myelin and myelin subfractions from rat brain during the active period of myelination. Proteolipid protein and DM-20 in myelin and myelin subfractions were readily acylated in developing rat brain 22 hours after intracerebral injection of [3H]palmitic acid. No differences in the relative specific activity of PLP in myelin from 9-, 15-, and 30-day-old rat brains was observed; however, the relative specific activity of PLP in the heavy myelin subfraction tended to be higher than that in the light myelin subfraction. The acylation of PLP was confirmed by fluorography of immuno-stained cellulose nitrate sheets, clearly establishing that the acylated protein is in fact the oligodendroglial cell- and myelin-specific protein, PLP. Since PLP is acylated in the 9-day-old animal, when little compact myelin is present, it is possible that the acylation of PLP is a prerequisite for the incorporation of this protein into the myelin membrane

1983-01-01

93

Topology and organization of bovine brain myelin proteolipid  

Energy Technology Data Exchange (ETDEWEB)

Myeline proteolipid protein (PLP), the mayor myeline protein in the central nervous system in an extremely hydrophobic membrane protein. Its relative abundance in myelin and lack of known enzymatic activity suggest that it may play an important role in the development and maintenance of the multilamellar structure of myelin. On the basis of primary sequence data, two conformational models of PLP have been proposed. To test these models, the author have attempted to locate thiol groups and disulfide bonds of PLP to determine which extramembrane fragments are located at the exterior and which at the interior faces of myelin membrane. /sup 14/C-Carboxamidomethylated PLP was fragmented by chymotrypsin, and the resulting mixture was separated by reverse-phase high performance liquid chromatography. All of the purified /sup 14/C-labeled peptides and disulfide containing peptides were further characterized by amino acid analysis. Two thiol groups (Cys-32 and Cys-34) and one disulfide bond between Cys-200 and Cys-219 were found. Unfortunately much of the fragmented protein proved intractable and the status of the other Cys residues was not determined.

Shaw, S.Y.

1988-01-01

94

Topology and organization of bovine brain myelin proteolipid  

International Nuclear Information System (INIS)

Myeline proteolipid protein (PLP), the mayor myeline protein in the central nervous system in an extremely hydrophobic membrane protein. Its relative abundance in myelin and lack of known enzymatic activity suggest that it may play an important role in the development and maintenance of the multilamellar structure of myelin. On the basis of primary sequence data, two conformational models of PLP have been proposed. To test these models, the author have attempted to locate thiol groups and disulfide bonds of PLP to determine which extramembrane fragments are located at the exterior and which at the interior faces of myelin membrane. 14C-Carboxamidomethylated PLP was fragmented by chymotrypsin, and the resulting mixture was separated by reverse-phase high performance liquid chromatography. All of the purified 14C-labeled peptides and disulfide containing peptides were further characterized by amino acid analysis. Two thiol groups (Cys-32 and Cys-34) and one disulfide bond between Cys-200 and Cys-219 were found. Unfortunately much of the fragmented protein proved intractable and the status of the other Cys residues was not determined

1988-01-01

95

Myelin imaging in amyotrophic and primary lateral sclerosis.  

UK PubMed Central (United Kingdom)

Primary lateral sclerosis (PLS) has been regarded as a rare, extreme form of amyotrophic lateral sclerosis (ALS). Like ALS, it is a clinical diagnosis without established biomarkers. We sought to explore loss of cerebral myelin in relation to clinical features, including cognitive impairment, in cases of both ALS and PLS. A novel MRI sequence (mcDESPOT) sensitive to water pools within myelin and intra- and extra-cellular spaces was applied to 23 ALS patients, seven PLS patients and 12 healthy controls, with interval follow-up in 15 ALS and four PLS patients. Results demonstrated that PLS patients were distinguished by widespread cerebral myelin water fraction reductions, independent of disease duration and clinical upper motor neuron burden. ALS patients showed a significant increase in intra- and extra-cellular water, indirectly linked to neuroinflammatory activity. Limited measures of cognitive impairment in the ALS group were associated with myelin changes within the anterior corpus callosum and frontal lobe projections. Longitudinal changes were only significant in the PLS group. In conclusion, in this exploratory study, myelin imaging has potential to distinguish PLS from ALS, and may have value as a marker of extramotor involvement. PLS may be a more active cerebral pathological process than its rate of clinical deterioration suggests.

Kolind S; Sharma R; Knight S; Johansen-Berg H; Talbot K; Turner MR

2013-05-01

96

Inactivation of myelin-associated glycoprotein enhances optic nerve regeneration.  

UK PubMed Central (United Kingdom)

CNS regeneration in higher vertebrates is a long sought after goal in neuroscience. The lack of regeneration is attributable in part to inhibitory factors found in myelin (Caroni and Schwab, 1988a). Myelin-associated glycoprotein (MAG) is an abundant myelin protein that inhibits neurite outgrowth in vitro (McKerracher et al., 1994; Mukhopadhyay et al., 1994), but its role in regeneration remains controversial. To address this role, we performed nerve crush on embryonic day 15 chick retina-optic nerve explants and then acutely eliminated MAG function along the nerve using chromophore-assisted laser inactivation (CALI). CALI of MAG permitted significant regrowth of retinal axons past the site of lesion containing CNS myelin in contrast to various control treatments. Electron microscopy of the site of nerve crush shows abundant regenerating axons crossing the gap. When crushed optic nerve was retrogradely labeled at the nerve stump, no labeling of retinal neurons was observed. In contrast, labeling of CALI of MAG-treated crushed optic nerve showed significant retinal labeling (89 +/- 16 cells per square millimeter), a value indistinguishable from that seen with non-crushed nerve (98 +/- 13 cells per square millimeter). These findings implicate MAG as an important component of the myelin-derived inhibition of nerve regeneration. The acute loss of MAG function can promote significant axon growth across a site of CNS nerve damage.

Wong EV; David S; Jacob MH; Jay DG

2003-04-01

97

Bimodal occurrence of aspartoacylase in myelin and cytosol of brain.  

Science.gov (United States)

The growing use of N-acetylaspartate as an indicator of neuronal viability has fostered interest in the biological function(s) of this unusual amino acid derivative. In considering the various physiological roles that have been proposed for this relatively abundant molecule one is obliged to take into account its unusual metabolic compartmentalization, according to which synthesis and storage occur in the neuron and hydrolytic cleavage in the oligodendrocyte. The latter reaction, catalyzed by aspartoacylase (ASPA), produces acetyl groups plus aspartate and has been proposed to occur in both soluble and membranous subfractions of white matter. Our study supports such bimodal occurrence and we now present immunoblot, proteomic, and biochemical evidence that the membrane-bound form of ASPA is intrinsic to purified myelin membranes. This was supported by a novel TLC-based method for the assay of ASPA. That observation, together with previous demonstrations of numerous lipid-synthesizing enzymes in myelin, suggests utilization of acetyl groups liberated by myelin-localized ASPA for lipid synthesis within the myelin sheath. Such synthesis might be selective and could explain the deficit of myelin lipids in animals lacking ASPA. PMID:17254025

Wang, Jianfeng; Matalon, Reuben; Bhatia, Gita; Wu, Gusheng; Li, Hong; Liu, Tong; Lu, Zi-Hua; Ledeen, Robert W

2007-01-24

98

Epineurial adipocytes are dispensable for Schwann cell myelination.  

Science.gov (United States)

Previous clinical observations and data from mouse models with defects in lipid metabolism suggested that epineurial adipocytes may play a role in peripheral nervous system myelination. We have used adipocyte-specific Lpin1 knockout mice to characterize the consequences of the presence of impaired epineurial adipocytes on the myelinating peripheral nerve. Our data revealed that the capacity of Schwann cells to establish myelin, and the functional properties of peripheral nerves, were not affected by compromised epineurial adipocytes in adipocyte-specific Lpin1 knockout mice. To evaluate the possibility that Lpin1-negative adipocytes are still able to support endoneurial Schwann cells, we also characterized sciatic nerves from mice carrying epiblast-specific deletion of peroxisome proliferator-activated receptor gamma, which develop general lipoatrophy. Interestingly, even the complete loss of adipocytes in the epineurium of peroxisome proliferator-activated receptor gamma knockout mice did not lead to detectable defects in Schwann cell myelination. However, probably as a consequence of their hyperglycemia, these mice have reduced nerve conduction velocity, thus mimicking the phenotype observed under diabetic condition. Together, our data indicate that while adipocytes, as regulators of lipid and glucose homeostasis, play a role in nerve function, their presence in epineurium is not essential for establishment or maintenance of proper myelin. PMID:22849425

Nadra, Karim; Médard, Jean-Jacques; Quignodon, Laure; Verheijen, Mark H G; Desvergne, Béatrice; Chrast, Roman

2012-10-10

99

Mini-Split  

CERN Multimedia

The lack of evidence for new physics beyond the standard model at the LHC points to a paucity of new particles near the weak scale. This suggests that the weak scale is tuned and that supersymmetry, if present at all, is realized at higher energies. The measured Higgs mass constrains the scalar sparticles to be below 10^5 TeV, while gauge coupling unification favors Higgsinos below 100 TeV. Nevertheless, in many models gaugino masses are suppressed and remain within reach of the LHC. Tuning the weak scale and the renormalization group evolution of the scalar masses constrain Split model building. Due to the small gaugino masses, either the squarks or the up-higgs often run tachyonic; in the latter case, successful electroweak breaking requires heavy higgsinos near the scalar sparticles. We discuss the consequences of tuning the weak scale and the phenomenology of several models of Split supersymmetry including anomaly mediation, U(1)_(B-L) mediation, and Split gauge mediation.

Arvanitaki, Asimina; Dimopoulos, Savas; Villadoro, Giovanni

2012-01-01

100

Lateral reorganization of myelin lipid domains by myelin basic protein studied at the air-water interface.  

UK PubMed Central (United Kingdom)

It has been speculated that adsorption of myelin basic protein (MBP) to the myelin lipid membrane leads to lateral reorganization of the lipid molecules within the myelin membrane. This hypothesis was tested in this study by surface pressure measurement and fluorescent imaging of a monolayer composed of a myelin lipid mixture. The properties of the lipid monolayer before and after addition of MBP into the subphase were monitored. Upon addition of MBP to the monolayer subphase, the surface pressure rose and significant rearrangement of the lipid domains was observed. These results suggest that binding and partial insertion of MBP into the lipid monolayer led to dramatic rearrangement and morphological changes of the lipid domains. A model of adsorption of MBP to the lipid domains and subsequent domain fusion promoted by minimization of electrostatic repulsion between the domains was proposed to account for the experimental observations. The significance of these results in light of the role of MBP in maintaining the myelin structural integrity is discussed.

Hu Y; Israelachvili J

2008-03-01

 
 
 
 
101

Defeating inhibition of regeneration by scar and myelin components.  

UK PubMed Central (United Kingdom)

Axon regeneration and the sprouting processes that underlie plasticity are blocked by inhibitory factors in the central nervous system (CNS) environment, several of which are upregulated after injury. The major inhibitory molecules are those associated with myelin and those associated with the glial scar. In myelin, NogoA, MAG, and OMgp are present on normal oligodendrocytes and on myelin debris. They act partly via the Nogo receptor, partly via an unidentified amino-Nogo receptor. In the glial scar, chondroitin sulphate proteoglycans, semaphorins, and the formation of a collagen-based membrane are all inhibitory. Methods to counteract these forms of inhibition have been identified, and these treatments promote axon regeneration in the damaged spinal cord, and in some cases recovery of function through enhanced plasticity.

Fawcett JW; Schwab ME; Montani L; Brazda N; Müller HW

2012-01-01

102

Alagille syndrome associated with myelinated retinal nerve fibers.  

UK PubMed Central (United Kingdom)

PURPOSE: Alagille syndrome is frequently associated with optic disc anomalies. This is the first report of a patient with Alagille syndrome and myelinated retinal nerve fibers. METHODS: A 5-year-old female patient was referred to the Centre for Ophthalmology before a liver transplantation. Ocular examinations including slit lamp examination and funduscopy as well as anterior segment and fundus images were performed. RESULTS: We observed myelinated retinal nerve fibers in both eyes of a 5-year-old female patient with Alagille syndrome. CONCLUSIONS: A broad spectrum of ocular anomalies is associated with Alagille syndrome. To our knowledge, this is the first reported case of myelinated retinal nerve fibers in a patient with Alagille syndrome.

Voykov B; Guenova E; Sturm E; Deuter C

2009-01-01

103

Aspartoacylase deficiency affects early postnatal development of oligodendrocytes and myelination.  

UK PubMed Central (United Kingdom)

Canavan disease (CD) is a neurodegenerative disease, caused by a deficiency in the enzyme aspartoacylase (ASPA). This enzyme has been localized to oligodendrocytes; however, it is still undefined how ASPA deficiency affects oligodendrocyte development. In normal mice the pattern of ASPA expression coincides with oligodendrocyte maturation. Therefore, postnatal oligodendrocyte maturation was analyzed in ASPA-deficient mice (CD mice). Early in development, CD mice brains showed decreased expression of neural cell markers that was later compensated. In addition, the levels of myelin proteins were decreased along with abnormal myelination in CD mice compared to wild-type (WT). These defects were associated with increased global levels of acetylated histone H3, decreased chromatin compaction and increased GFAP protein, a marker for astrogliosis. Together, these findings strongly suggest that, early in postnatal development, ASPA deficiency affects oligodendrocyte maturation and myelination.

Mattan NS; Ghiani CA; Lloyd M; Matalon R; Bok D; Casaccia P; de Vellis J

2010-11-01

104

Aspartoacylase deficiency affects early postnatal development of oligodendrocytes and myelination.  

Science.gov (United States)

Canavan disease (CD) is a neurodegenerative disease, caused by a deficiency in the enzyme aspartoacylase (ASPA). This enzyme has been localized to oligodendrocytes; however, it is still undefined how ASPA deficiency affects oligodendrocyte development. In normal mice the pattern of ASPA expression coincides with oligodendrocyte maturation. Therefore, postnatal oligodendrocyte maturation was analyzed in ASPA-deficient mice (CD mice). Early in development, CD mice brains showed decreased expression of neural cell markers that was later compensated. In addition, the levels of myelin proteins were decreased along with abnormal myelination in CD mice compared to wild-type (WT). These defects were associated with increased global levels of acetylated histone H3, decreased chromatin compaction and increased GFAP protein, a marker for astrogliosis. Together, these findings strongly suggest that, early in postnatal development, ASPA deficiency affects oligodendrocyte maturation and myelination. PMID:20637282

Mattan, Natalia S; Ghiani, Cristina A; Lloyd, Marcia; Matalon, Reuben; Bok, Dean; Casaccia, Patrizia; de Vellis, Jean

2010-07-14

105

Rapid myelin water content mapping on clinical MR systems  

Energy Technology Data Exchange (ETDEWEB)

We present an algorithm for the fast mapping of myelin water content using standard multiecho gradient echo acquisitions of the human brain. The method extents a previously published approach for the simultaneous measurement of brain T{sub 1}, T{sup *}{sub 2} and total water content. Employing the multiexponential T{sup *}{sub 2} decay signal of myelinated tissue, myelin water content was measured based on the quantification of two water pools ('myelin water' and 'rest') with different relaxation times. As the existing protocol was focussed on the fast mapping of quantitative MR parameters with whole brain coverage in clinically relevant measurement times, the sampling density of the T{sup *}{sub 2} curve was compromised to 10 echo times with a T {sub Emax} of approx. 40 ms. Therefore, pool amplitudes were determined using a quadratic optimisation approach. The optimisation was constrained by including a priori knowledge about brain water pools. All constraints were optimised in a simulation study to minimise systematic error sources given the incomplete knowledge about the real pool-specific relaxation properties. Based on the simulation results, whole brain in vivo myelin water content maps were acquired in 10 healthy controls and one subject with multiple sclerosis. The in vivo results obtained were consistent with previous reports which demonstrates that a simultaneous whole brain mapping of T{sub 1}, T{sup *}{sub 2}, total and myelin water content is feasible on almost any modern MR scanner in less than 10 minutes. (orig.)

Tonkova, Vyara; Arhelger, Volker [Fachhochschule Koblenz, RheinAhrCampus Remagen (Germany); Schenk, Jochen [Radiologisches Institut, Koblenz (Germany); Neeb, Heiko [Fachhochschule Koblenz, RheinAhrCampus Remagen (Germany); Koblenz Univ. (Germany). Inst. for Medical Engineering and Information Processing - MTI Mittelrhein

2012-07-01

106

Myelin lipid abnormalities in the aspartoacylase-deficient tremor rat.  

UK PubMed Central (United Kingdom)

The high concentration of N-acetylaspartate (NAA) in neurons of the central nervous system and its growing clinical use as an indicator of neuronal viability has intensified interest in the biological function of this amino acid derivative. The biomedical relevance of such inquiries is highlighted by the myelin-associated pathology of Canavan disease, an inherited childhood disorder resulting from mutation of aspartoacylase (ASPA), the NAA-hydrolyzing enzyme. This enzyme is known to be localized in oligodendrocytes with bimodal distribution in cytosol and the myelin sheath, and to produce acetyl groups utilized in myelin lipid synthesis. Loss of this acetyl source in Canavan disease and rodent models such as the tremor rat are thought to account for the observed myelin deficit. This study was undertaken to further define and quantify the specific lipid abnormalities that occur as a result of ASPA deficit in the tremor rat. Employing mass spectrometry together with high performance thin-layer chromatography, we found that myelin from 28-day-old animals showed major reduction in cerebrosides (CB) and sulfatides (Sulf) with unsubstituted fatty acids, and equal if not greater changes in myelin from 7-month-old tremors. Cerebrosides with 2-hydroxyfatty acids showed little if any change at either age; Sulf with 2-hydroxyfatty acids showed no significant change at 28 days, but surprisingly a major increase at 7 months. Two species of phosphatidylcholine, 32:0 and 34:1, also showed significant increase, but only at 28 days. One form of phosphatidylethanolamine, PE36:1, was reduced a modest amount at both ages, whereas the plasmalogen form did not change. The dysmyelination that results from inactivation of ASPA is thus characterized by selective decreases as well as some increases in specific lipids.

Wang J; Leone P; Wu G; Francis JS; Li H; Jain MR; Serikawa T; Ledeen RW

2009-01-01

107

Myelin lipid abnormalities in the aspartoacylase-deficient tremor rat.  

Science.gov (United States)

The high concentration of N-acetylaspartate (NAA) in neurons of the central nervous system and its growing clinical use as an indicator of neuronal viability has intensified interest in the biological function of this amino acid derivative. The biomedical relevance of such inquiries is highlighted by the myelin-associated pathology of Canavan disease, an inherited childhood disorder resulting from mutation of aspartoacylase (ASPA), the NAA-hydrolyzing enzyme. This enzyme is known to be localized in oligodendrocytes with bimodal distribution in cytosol and the myelin sheath, and to produce acetyl groups utilized in myelin lipid synthesis. Loss of this acetyl source in Canavan disease and rodent models such as the tremor rat are thought to account for the observed myelin deficit. This study was undertaken to further define and quantify the specific lipid abnormalities that occur as a result of ASPA deficit in the tremor rat. Employing mass spectrometry together with high performance thin-layer chromatography, we found that myelin from 28-day-old animals showed major reduction in cerebrosides (CB) and sulfatides (Sulf) with unsubstituted fatty acids, and equal if not greater changes in myelin from 7-month-old tremors. Cerebrosides with 2-hydroxyfatty acids showed little if any change at either age; Sulf with 2-hydroxyfatty acids showed no significant change at 28 days, but surprisingly a major increase at 7 months. Two species of phosphatidylcholine, 32:0 and 34:1, also showed significant increase, but only at 28 days. One form of phosphatidylethanolamine, PE36:1, was reduced a modest amount at both ages, whereas the plasmalogen form did not change. The dysmyelination that results from inactivation of ASPA is thus characterized by selective decreases as well as some increases in specific lipids. PMID:18478328

Wang, Jianfeng; Leone, Paola; Wu, Gusheng; Francis, Jeremy S; Li, Hong; Jain, Mohit Raja; Serikawa, Tadao; Ledeen, Robert W

2008-05-14

108

Developmental increase of aspartoacylase in oligodendrocytes parallels CNS myelination.  

UK PubMed Central (United Kingdom)

Canavan disease, an autosomal-recessive neurogenetic disorder, is caused by mutations in aspartoacylase, an enzyme that deacetylates N-acetylaspartate to generate free acetate in the brain. Earlier studies have shown that aspartoacylase is primarily restricted to myelin synthesizing cells (oligodendroglia) in the CNS. These findings have led us to investigate the developmental expression of aspartoacylase gene in the rat brain in an attempt to shed more light on the role of this enzyme in myelination. In situ hybridization using a 35S riboprobe based on murine aspartoacylase cDNA was used in this study. The probe hybridized mostly to the white matter tracts with different densities depending on the age of the animal and region of the brain examined. Little or no hybridization signals were detected in the 1-day-old rats, whereas the signal was clearly detectable in most of the white matter regions of the CNS in the 11-day-old rats. The signal density markedly increased at postnatal day 17, the peak of myelination. Thereafter, the hybridization signals decreased somewhat but still could be observed in the adult animals. Thus, the developmental expression pattern of aspartoacylase gene in the postnatal brain closely parallels myelination in the CNS. In the CNS, the hybridization signal of ASPA appeared to be restricted primarily to oligodendrocytes, the primary myelin synthesizing cell type in the CNS. However, the signal was not detectable in rat sciatic nerve (Schwann cells) of the peripheral nervous system. These findings indicate that the role of N-acetylaspartate in myelin synthesis is restricted to the CNS. Furthermore, they provide additional support for the acetate deficiency hypothesis of Canavan disease and also make a stronger case for acetate supplementation as an immediate and inexpensive therapy for Canavan disease.

Kirmani BF; Jacobowitz DM; Namboodiri MA

2003-01-01

109

Rotational Splitting of Pulsational Modes  

CERN Document Server

Mode splittings produced by uniform rotation and a particular form of differential rotation are computed for two-dimensional rotating 10 Mo ZAMS stellar models. The change in the character of the mode splitting is traced as a function of uniform rotation rate, and it is found that only relatively slow rotation rates are required before the mode splitting becomes asymmetric about the azimuthally symmetric (m=0) mode. Increased rotation produces a progressively altered pattern of the individual modes with respect to each other. Large mode splittings begin to overlap with the mode splittings produced by different radial and latitudinal modes at relatively low rotation rates. The mode splitting pattern for the differentially rotating stars we model is different than that for uniformly rotating stars, making the mode splitting a possible discriminant of the internal angular momentum distribution if one assumes the formidable challenge of mode identification can be overcome.

Deupree, Robert

2010-01-01

110

TREATMENT OF BRAIN CHANGES WITH MYELIN PROTECTIVE AGENTS  

UK PubMed Central (United Kingdom)

A method is proposed to treat with myelin protective agents Alzheimer's disease and other conditions satisfying the retrogenic neuropathologic vulnerability model. These conditions include normal brain aging, mild cognitive impairment and specific non-AD dementing disorders. Such agents are vitamin B-12 (cobalamin), homocysteine modulators (containing vitamin B-12, folate [folic acid], vitamin B-6 [pyridoxine] and/or betain [trimethylglycine]), a calpain-inhibitor, or interferon-beta. Another treatment is to maintain lipid reparative mechanisms to lessen the progressive destruction of myelin pathways in the patient's brain. Such reparative mechanisms are cholesterol levels or cholesterol transport.

REISBERG Barry; FRANSSEN Emil H.

111

Analysis of Gpr126 function defines distinct mechanisms controlling the initiation and maturation of myelin.  

Science.gov (United States)

In peripheral nerves, Schwann cells form the myelin sheath, which allows the efficient propagation of action potentials along axons. The transcription factor Krox20 regulates the initiation of myelination in Schwann cells and is also required to maintain mature myelin. The adhesion G protein-coupled receptor (GPCR) Gpr126 is essential for Schwann cells to initiate myelination, but previous studies have not addressed the role of Gpr126 signaling in myelin maturation and maintenance. Through analysis of Gpr126 in zebrafish, we define two distinct mechanisms controlling the initiation and maturation of myelin. We show that gpr126 mutant Schwann cells elaborate mature myelin sheaths and maintain krox20 expression for months, provided that the early signaling defect is bypassed by transient elevation of cAMP. At the onset of myelination, Gpr126 and protein kinase A (PKA) function as a switch that allows Schwann cells to initiate krox20 expression and myelination. After myelination is initiated, krox20 expression is maintained and myelin maturation proceeds independently of Gpr126 signaling. Transgenic analysis indicates that the Krox20 cis-regulatory myelinating Schwann cell element (MSE) becomes active at the onset of myelination and that this activity is dependent on Gpr126 signaling. Activity of the MSE declines after initiation, suggesting that other elements are responsible for maintaining krox20 expression in mature nerves. We also show that elevated cAMP does not initiate myelination in the absence of functional Neuregulin 1 (Nrg1) signaling. These results indicate that the mechanisms regulating the initiation of myelination are distinct from those mediating the maturation and maintenance of myelin. PMID:23804499

Glenn, Thomas D; Talbot, William S

2013-06-26

112

Stereotypes, stepmothers, and splitting.  

UK PubMed Central (United Kingdom)

Asserting that preteen children cannot tolerate ambivalence, a recent study extols the "wicked stepmother" stereotype in fairy tales for providing a safe outlet for child-mother aggression. However, even theories which consider splitting normal in object-relations development see it as operating mostly before age 3. Dualistic thinking is not ubiquitous in childhood, nor is it ever outgrown. Rather, it is a mode of organizing experience mythopoetically; we learn to minimize its intrusions in dealings with day-to-day realities. There is no scientific justification for (and there are moral objections to) the propagation of the wicked stepmother stereotype.

Radomisli M

1981-01-01

113

Intraneuronal N-acetylaspartate supplies acetyl groups for myelin lipid synthesis: evidence for myelin-associated aspartoacylase.  

UK PubMed Central (United Kingdom)

Despite its growing use as a radiological indicator of neuronal viability, the biological function of N-acetylaspartate (NAA) has remained elusive. This is due in part to its unusual metabolic compartmentalization wherein the synthetic enzyme occurs in neuronal mitochondria whereas the principal metabolizing enzyme, N-acetyl-L-aspartate amidohydrolase (aspartoacylase), is located primarily in white matter elements. This study demonstrates that within white matter, aspartoacylase is an integral component of the myelin sheath where it is ideally situated to produce acetyl groups for synthesis of myelin lipids. That it functions in this manner is suggested by the fact that myelin lipids of the rat optic system are well labeled following intraocular injection of [14C-acetyl]NAA. This is attributed to uptake of radiolabeled NAA by retinal ganglion cells followed by axonal transport and transaxonal transfer of NAA into myelin, a membrane previously shown to contain many lipid synthesizing enzymes. This study identifies a group of myelin lipids that are so labeled by neuronal [14C]NAA, and demonstrates a different labeling pattern from that produced by neuronal [14C]acetate. High performance liquid chromatographic analysis of the deproteinated soluble materials from the optic system following intraocular injection of [14C]NAA revealed only the latter substance and no radiolabeled acetate, suggesting little or no hydrolysis of NAA within mature neurons of the optic system. These results suggest a rationale for the unusual compartmentalization of NAA metabolism and point to NAA as a neuronal constituent that is essential for the formation and/or maintenance of myelin. The relevance of these findings to Canavan disease is discussed.

Chakraborty G; Mekala P; Yahya D; Wu G; Ledeen RW

2001-08-01

114

Myelin and myelinization in the telencephalon and mesencephalon of the lizard Gallotia galloti as revealed by the immunohistochemical localization of myelin basic protein.  

UK PubMed Central (United Kingdom)

We have studied in the telencephalon and mesencephalon of the lizard Gallotia galloti the localization and the chronology of appearance of the immunoreactivity due to the presence of a myelin-specific protein: the Myelin Basic Protein (MBP). MBP-like immunoreactivity was present with different degrees of intensity in many nerve fibers (isolated, in tracts and in commissurae) and it was apparently more abundant in mesencephalon. During ontogeny the earliest MBP-like immunoreactivity was detected at E.36 in few tracts in mesencephalon and appeared at E.40 in telencephalon, proceeding caudo-rostrally and from the ventral (basal) to the dorsal (alar) regions. Accumulation of MBP continued after hatching. Oligodendrocyte cell bodies were not immunopositive, not even at the youngest ages studied.

Yanes C; Monzon-Mayor M; de Barry J; Gombos G

1992-01-01

115

Myelin and myelinization in the telencephalon and mesencephalon of the lizard Gallotia galloti as revealed by the immunohistochemical localization of myelin basic protein.  

Science.gov (United States)

We have studied in the telencephalon and mesencephalon of the lizard Gallotia galloti the localization and the chronology of appearance of the immunoreactivity due to the presence of a myelin-specific protein: the Myelin Basic Protein (MBP). MBP-like immunoreactivity was present with different degrees of intensity in many nerve fibers (isolated, in tracts and in commissurae) and it was apparently more abundant in mesencephalon. During ontogeny the earliest MBP-like immunoreactivity was detected at E.36 in few tracts in mesencephalon and appeared at E.40 in telencephalon, proceeding caudo-rostrally and from the ventral (basal) to the dorsal (alar) regions. Accumulation of MBP continued after hatching. Oligodendrocyte cell bodies were not immunopositive, not even at the youngest ages studied. PMID:1373587

Yanes, C; Monzon-Mayor, M; de Barry, J; Gombos, G

1992-01-01

116

Splitting the Cartesian point  

Energy Technology Data Exchange (ETDEWEB)

It is argued that the point structure of space and time must be constructed from the primitive extensional character of space and time. A procedure for doing this is laid down and applied to one-dimensional and two-dimensional systems of abstract extensions. Topological and metrical properties of the constructed point systems, which differ nontrivially from the usual R and R/sup 2/ models, are examined. Briefly, constructed points are associated with directions and the Cartesian point is split. In one-dimension each point splits into a point pair compatible with the linear ordering. An application to one-dimensional particle motion is given, with the result that natural topological assumptions force the number of left point, right point transitions to remain locally finite in a continuous motion. In general, Cartesian points are seen to correspond to certain filters on a suitable Boolean algebra. Constructed points correspond to ultrafilters. Thus, point construction gives a natural refinement of the Cartesian systems.

Blodwell, J.F.

1987-10-01

117

Myelin gangliosides of human peripheral nervous system: an enrichment of GM1 in the motor nerve myelin isolated from cauda equina.  

UK PubMed Central (United Kingdom)

Myelins of the PNS were isolated from human motor and sensory nerves of cauda equina, and their ganglioside compositions were compared. The predominant ganglioside in the human PNS myelins, both from motor and sensory nerves, was LM1 (sialosylneolactotetraosylceramide). Sialosyl-nLc6Cer and disialosyl-nLc4Cer, GD3, GM3, and GD1b were detected as common components of the two nerve myelins. Furthermore, it was revealed that the motor nerve myelin contained GM1 (about 15% of total gangliosides), whereas sensory nerve myelin contained only a trace amount of GM1 (less than 5%), by TLC analyses together with TLC immunostaining using anti-GM1 antibody. As for the disialoganglioside fraction, the content of GD1a, as well as that of GM1, differed in motor and sensory nerves. Thus, the different contents of the ganglioseries gangliosides in human motor and sensory nerve myelins were demonstrated.

Ogawa-Goto K; Funamoto N; Ohta Y; Abe T; Nagashima K

1992-11-01

118

[Lyme borreliosis--incidence of serum anti-myelin antibodies  

UK PubMed Central (United Kingdom)

The method of enzyme immunoassay (ELISA) was used for detection of antibodies against the basic protein myelin (antimyelin antibodies) for a group of serum samples (n 36) with positive anti-borrelia immunoglobulins IgG and IgM (ELISA-Borrelia afzelii) and their immune complexes (ELISA-PEG). Antimyelin antibodies (ELISA-Doxa Kit-Myelin Basic Protein Antibodies) were assessed in 31% (n 11) of examined serum samples of patients with the working diagnosis of Lyme borreliosis. Statistical analysis (p 0.07) confirmed a more frequent incidence of antimyelin antibodies in younger female subjects (age 31 years) as compared with a group of sera (n 25) where the authors did not record the formation of immunoglobulins against the basic myelin protein (age 51 years). Neither the value of titres nor the frequency of detected anti-borrelia IgG and IgM and immune complexes did not differ significantly in the two groups. From the assembled results ensues that in the course of Lyme borreliosis, in chronic affection of organs an autoimmune reaction may develop where the basic myelin protein is damaged (demyelinizatio) and subsequently antimyelin antibodies are formed.

Rysková O; Vyslouzil L; Honegr K; Lesná J; Horácek J; Skrabková Z

2002-04-01

119

[Lyme borreliosis--incidence of serum anti-myelin antibodies].  

Science.gov (United States)

The method of enzyme immunoassay (ELISA) was used for detection of antibodies against the basic protein myelin (antimyelin antibodies) for a group of serum samples (n 36) with positive anti-borrelia immunoglobulins IgG and IgM (ELISA-Borrelia afzelii) and their immune complexes (ELISA-PEG). Antimyelin antibodies (ELISA-Doxa Kit-Myelin Basic Protein Antibodies) were assessed in 31% (n 11) of examined serum samples of patients with the working diagnosis of Lyme borreliosis. Statistical analysis (p 0.07) confirmed a more frequent incidence of antimyelin antibodies in younger female subjects (age 31 years) as compared with a group of sera (n 25) where the authors did not record the formation of immunoglobulins against the basic myelin protein (age 51 years). Neither the value of titres nor the frequency of detected anti-borrelia IgG and IgM and immune complexes did not differ significantly in the two groups. From the assembled results ensues that in the course of Lyme borreliosis, in chronic affection of organs an autoimmune reaction may develop where the basic myelin protein is damaged (demyelinizatio) and subsequently antimyelin antibodies are formed. PMID:11987581

Rysková, O; Vyslouzil, L; Honegr, K; Lesná, J; Horácek, J; Skrabková, Z

2002-04-01

120

Increased Th17 response to myelin peptides in pediatric MS.  

UK PubMed Central (United Kingdom)

Studies of the underlying immune mechanisms of multiple sclerosis (MS) in children may shed light on the initial events of MS pathogenesis. We studied T cell responses to myelin peptides in 10 pediatric MS patients (PMS), 10 pediatric healthy controls (PHC), 10 adult MS patients (AMS) and 10 adult healthy controls (AHC). A significantly higher proportion of divided CD4+ T cell responses in response to myelin peptides by the CFSE assay in PMS compared to PHC at both concentrations of myelin peptide tested (t test, 95% CI, p=0.0067 for MP1; p=0.0086 for MP10), and between PMS and AMS (p=0.0012 at 1 ?g/mL of myelin peptides, p<0.0001 at 10 ?g/mL) was found. In addition, T cells with a central memory phenotype producing IL-17 were increased in PMS compared to PHC (p<0.05). IL-7 levels in culture supernatants were elevated in PMS compared to PHC and AMS (t test<0.01).

Vargas-Lowy D; Kivisäkk P; Gandhi R; Raddassi K; Soltany P; Gorman MP; Khoury SJ; Chitnis T

2013-03-01

 
 
 
 
121

The effect of DDT and dieldrin on myelinated nerve fibres  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The effects of the chlorinated hydrocarbon insecticides, DDT and dieldrin, on myelinated nerve fibres of the clawed toad, Xenopus laevis, were studied by recording compound action nerve fibres, and membrane potentials of single nodes of Ranvier. The effect of DDT (5 × 10?4 M) was found to be exclusi...

Bercken, J. van den

122

Postnatal dietary fat influences mRNAS involved in myelination.  

Science.gov (United States)

The synthesis and composition of myelin in the developing mouse central nervous system can be influenced by diet. Postnatal maternal fat intake altered nursing pup brain and liver fatty acid composition. Peak (day 21) proteolipid protein (PLP) and myelin basic protein (MBP) mRNA levels were reduced when pups were nursed by mothers fed a fat-free or 5% coconut oil diet. This effect was reversed by feeding a corn oil based diet. Oleic acid accounts for about 30% of myelin fatty acids. mRNA levels of stearoyl CoA desaturase (SCD), the rate-limiting step in oleic acid synthesis, increase in neonatal mouse brain. Postnatal maternal fat-free feeding reduced day 21 pup brain SCD and LDL receptor, but not apolipoprotein (Apo E) E mRNA levels. In contrast to brain, nursing pup hepatic SCD mRNA levels were induced, LDL receptor mRNA levels were unaffected and Apo E mRNA levels were reduced by postnatal maternal fat-free feeding. Myelin-specific mRNA levels are developmentally regulated and influenced by dietary fat. Neonatal brain SCD and LDL receptor mRNA levels are also altered by neonatal fat intake. The neonatal response to dietary fat is tissue-specific at the mRNA level. PMID:1350977

DeWille, J W; Farmer, S J

1992-01-01

123

Postnatal dietary fat influences mRNAS involved in myelination.  

UK PubMed Central (United Kingdom)

The synthesis and composition of myelin in the developing mouse central nervous system can be influenced by diet. Postnatal maternal fat intake altered nursing pup brain and liver fatty acid composition. Peak (day 21) proteolipid protein (PLP) and myelin basic protein (MBP) mRNA levels were reduced when pups were nursed by mothers fed a fat-free or 5% coconut oil diet. This effect was reversed by feeding a corn oil based diet. Oleic acid accounts for about 30% of myelin fatty acids. mRNA levels of stearoyl CoA desaturase (SCD), the rate-limiting step in oleic acid synthesis, increase in neonatal mouse brain. Postnatal maternal fat-free feeding reduced day 21 pup brain SCD and LDL receptor, but not apolipoprotein (Apo E) E mRNA levels. In contrast to brain, nursing pup hepatic SCD mRNA levels were induced, LDL receptor mRNA levels were unaffected and Apo E mRNA levels were reduced by postnatal maternal fat-free feeding. Myelin-specific mRNA levels are developmentally regulated and influenced by dietary fat. Neonatal brain SCD and LDL receptor mRNA levels are also altered by neonatal fat intake. The neonatal response to dietary fat is tissue-specific at the mRNA level.

DeWille JW; Farmer SJ

1992-01-01

124

iOPs: a new tool for studying myelin pathologies?  

UK PubMed Central (United Kingdom)

Generating patient-specific oligodendrocyte progenitors capable of repairing myelination defects observed in multiple neurological afflictions holds great therapeutic potential. Recently in Nature Biotechnology, Najm et al. (2013) and Yang et al. (2013) generated these progenitors by direct reprogramming, bringing us closer to their use in disease analysis and autologous transplantation strategies.

Noble M; Mayer-Pröschel M; Pröschel C

2013-05-01

125

Myelin basic protein is affected by reduced synthesis of myelin proteolipid protein in the jimpy mouse.  

UK PubMed Central (United Kingdom)

Myelin basic proteins (MBPs) from 6-day-old, 10-day-old, 20-day-old and adult normal mouse brain were compared with those from 20-day-old jimpy (dysmyelinating mutant) mouse brain to determine the effect of reduced levels of proteolipid protein (PLP) on MBPs. Alkaline-urea-gel electrophoresis showed that 6-day-old and 10-day-old normal and jimpy MBPs lacked charge microheterogeneity, since C8 (the least cationic of the components; not be confused with complement component C8) was the only charge isomer present. In contrast, MBPs from 20-day-old and adult normal mouse brain displayed extensive charge microheterogeneity, having at least eight components. A 32 kDa MBP was the major isoform observed on immunoblots of acid-soluble protein from 6-day-old and 10-day-old normal and 20-day-old jimpy mouse brain. There were eight bands present in 20-day-old and adult normal mouse brain. Purified human MBP charge heteromers C1, C2, C3 and C4 reacted strongly with rat 14 kDa MBP antiserum, whereas the reaction with human C8 was weak. This suggested that MBPs from early-myelinating and jimpy mice did not react to MBP antisera because C8 was the major charge isomer in these animals. Purification of MBPs from normal and jimpy brain by alkaline-gel electrophoresis showed that both normal and jimpy MBPs have size heterogeneity when subjected to SDS/PAGE. However, the size isoforms in normal mouse brain (32, 21, 18.5, 17 and 14 kDa) differed from those in jimpy brain (32, 21, 20, 17, 15 and 14 kDa) in both size and relative amounts. Amino acid analyses of MBPs from jimpy brain showed an increase in glutamic acid, alanine and ornithine, and a decrease in histidine, arginine and proline. The changes in glutamic acid, ornithine and arginine are characteristic of the differences observed in human C8 when compared with C1.

Fannon AM; Moscarello MA

1990-05-01

126

The SPLIT research agenda 2013.  

UK PubMed Central (United Kingdom)

This review focuses on active clinical research in pediatric liver transplantation with special emphasis on areas that could benefit from studies utilizing the SPLIT infrastructure and data repository. Ideas were solicited by members of the SPLIT Research Committee and sections were drafted by members of the committee with expertise in those given areas. This review is intended to highlight priorities for clinical research that could successfully be conducted through the SPLIT collaborative and would have significant impact in pediatric liver transplantation.

Alonso EM; Ng VL; Anand R; Anderson CD; Ekong UD; Fredericks EM; Furuya KN; Gupta NA; Lerret SM; Sundaram S; Tiao G

2013-08-01

127

Geometrical splitting in Monte Carlo  

Energy Technology Data Exchange (ETDEWEB)

A statistical model is presented by which a direct statistical approach yielded an analytic expression for the second moment, the variance ratio, and the benefit function in a model of an n surface-splitting Monte Carlo game. In addition to the insight into the dependence of the second moment on the splitting parameters the main importance of the expressions developed lies in their potential to become a basis for in-code optimization of splitting through a general algorithm. Refs.

Dubi, A.; Elperin, T.; Dudziak, D.J.

1982-01-01

128

Identification of the protein target of myelin-binding ligands by immunohistochemistry and biochemical analyses.  

UK PubMed Central (United Kingdom)

The ability to visualize myelin is important in the diagnosis of demyelinating disorders and the detection of myelin-containing nerves during surgery. The development of myelin-selective imaging agents requires that a defined target for these agents be identified and that a robust assay against the target be developed to allow for assessment of structure-activity relationships. We describe an immunohistochemical analysis and a fluorescence polarization binding assay using purified myelin basic protein (MBP) that provides quantitative evidence that MBP is the molecular binding partner of previously described myelin-selective fluorescent dyes such as BMB, GE3082, and GE3111.

Bajaj A; LaPlante NE; Cotero VE; Fish KM; Bjerke RM; Siclovan T; Tan Hehir CA

2013-01-01

129

Fuel pin bundle splitting  

International Nuclear Information System (INIS)

The patent describes the splitting of a bundle of nuclear fuel pins into smaller bundles, during the dismantling of a fuel element, in preparation for the reprocessing of the spent fuel. The size of the small bundles are such that they are suitable for cropping in an easily maintainable shearing machine. The cropping of fuel pins into short sections exposes the irradiated fuel to be reprocessed. The invention involves feeding a number of blades into the exposed end of a fuel pin bundle. The bundle is forced out of the containing sheath by a ram, and the fuel pins are forced to pass either side of theblades, there by the bundle is sorted into a number of smaller bundles. (U.K.).

1986-10-21

130

Positronium Hyperfine Splitting  

CERN Document Server

Positronium is an ideal system for the research of QED in the bound state. The hyperfine splitting of positronium (Ps-HFS: about 203 GHz) is a good tool to test QED and also sensitive to new physics beyond the Standard Model. Previous experimental results show 3.9\\,$\\sigma$ (15 ppm) discrepancy from the QED $\\mathrm{O}\\left(\\alpha ^3 \\ln{1/\\alpha}\\right)$ prediction. We point out probable common systematic errors in all previous experiments. I measure the Ps-HFS in two different ways. (1) A prototype run without RF system is described first. (2) I explain a new direct Ps-HFS measurement without static magnetic field. The present status of the optimization studies and current design of the experiment are described. We are now taking data of a test experiment for the observation of the direct transition.

Miyazaki, Akira

2010-01-01

131

Axonal plasticity elicits long-term changes in oligodendroglia and myelinated fibers  

DEFF Research Database (Denmark)

Axons are linked to induction of myelination during development and to the maintenance of myelin and myelinated tracts in the adult CNS. Currently, it is unknown whether and how axonal plasticity in adult CNS impacts the myelinating cells and their precursors. In this article, we report that newly formed axonal sprouts are able to induce a protracted myelination response in adult CNS. We show that newly formed axonal sprouts, induced by lesion of the entorhino-hippocampal perforant pathway, have the ability to induce a myelination response in stratum radiatum and lucidum CA3. The lesion resulted in significant recruitment of newly formed myelinating cells, documented by incorporation of the proliferation marker bromodeoxyuridine into chondroitin sulphate NG2 expressing cells in stratum radiatum and lucidum CA3 early after lesion, and the occurrence of a 28% increase in the number of oligodendrocytes, of which some had incorporated bromodeoxyuridine, 9 weeks post-lesion. Additionally, a marked increase (41%) in myelinated fibres was detected in silver stained sections. Interestingly, these apparently new fibres achieved the same axon diameter as unlesioned mice but myelin thickness remained thinner than normal, suggesting that the sprouting axons in stratum radiatum and lucidum CA3 were not fully myelinated 9 weeks after lesion. Our combined results show that sprouting axons provide a strong stimulus to oligodendrocyte lineage cells to engage actively in the myelination processes in the adult CNS.

DrŘjdahl, Nina; Nielsen, Helle Hvilsted

2010-01-01

132

Trends and Properties of Human Cerebral Cortex: Correlations with Cortical Myelin Content.  

UK PubMed Central (United Kingdom)

"In vivo Brodmann mapping" or non-invasive cortical parcellation using MRI, especially by measuring cortical myelination, has recently become a popular research topic, though myeloarchitectonic cortical parcellation in humans previously languished in favor of cytoarchitecture. We review recent in vivo myelin mapping studies and discuss some of the different methods for estimating myelin content. We discuss some ways in which myelin maps may improve surface registration and be useful for cross-modal and cross-species comparisons, including some preliminary cross-species results. Next, we consider neurobiological aspects of why some parts of cortex are more myelinated than others. Myelin content is inversely correlated with intracortical circuit complexity-in general, more myelin content means simpler and perhaps less dynamic intracortical circuits. Using existing PET data and functional network parcellations, we examine metabolic differences in the differently myelinated cortical functional networks. Lightly myelinated cognitive association networks tend to have higher aerobic glycolysis than heavily myelinated early sensory-motor ones, perhaps reflecting greater ongoing dynamic anabolic cortical processes. This finding is consistent with the hypothesis that intracortical myelination may stabilize intracortical circuits and inhibit synaptic plasticity. Finally, we discuss the future of the in vivo myeloarchitectural field and cortical parcellation--"in vivo Brodmann mapping"--in general.

Glasser MF; Goyal MS; Preuss TM; Raichle ME; Van Essen DC

2013-04-01

133

A small peptide mimetic of brain-derived neurotrophic factor promotes peripheral myelination.  

Science.gov (United States)

The expression of the neurotrophins and their receptors is essential for peripheral nervous system development and myelination. We have previously demonstrated that brain-derived neurotrophic factor (BDNF) exerts contrasting influences upon Schwann cell myelination in vitro - promoting myelination via neuronally expressed p75NTR, but inhibiting myelination via neuronally expressed TrkB. We have generated a small peptide called cyclo-dPAKKR that structurally mimics the region of BDNF that binds p75NTR. Here, we have investigated whether utilizing cyclo-dPAKKR to selectively target p75NTR is an approach that could exert a unified promyelinating response. Like BDNF, cyclo-dPAKKR promoted myelination of nerve growth factor-dependent neurons in vitro, an effect dependent on the neuronal expression of p75NTR. Importantly, cyclo-dPAKKR also significantly promoted the myelination of tropomyosin-related kinase receptor B-expressing neurons in vitro, whereas BDNF exerted a significant inhibitory effect. This indicated that while BDNF exerted a contrasting influence upon the myelination of distinct subsets of dorsal root ganglion (DRG) neurons in vitro, cyclo-dPAKKR uniformly promoted their myelination. Local injection of cyclo-dPAKKR adjacent to the developing sciatic nerve in vivo significantly enhanced myelin protein expression and significantly increased the number of myelinated axons. These results demonstrate that cyclo-dPAKKR promotes peripheral myelination in vitro and in vivo, suggesting it is a strategy worthy of further investigation for the treatment of peripheral demyelinating diseases. PMID:23350698

Xiao, Junhua; Hughes, Richard A; Lim, Joe Y; Wong, Agnes W; Ivanusic, Jason J; Ferner, Anita H; Kilpatrick, Trevor J; Murray, Simon S

2013-02-24

134

A small peptide mimetic of brain-derived neurotrophic factor promotes peripheral myelination.  

UK PubMed Central (United Kingdom)

The expression of the neurotrophins and their receptors is essential for peripheral nervous system development and myelination. We have previously demonstrated that brain-derived neurotrophic factor (BDNF) exerts contrasting influences upon Schwann cell myelination in vitro - promoting myelination via neuronally expressed p75NTR, but inhibiting myelination via neuronally expressed TrkB. We have generated a small peptide called cyclo-dPAKKR that structurally mimics the region of BDNF that binds p75NTR. Here, we have investigated whether utilizing cyclo-dPAKKR to selectively target p75NTR is an approach that could exert a unified promyelinating response. Like BDNF, cyclo-dPAKKR promoted myelination of nerve growth factor-dependent neurons in vitro, an effect dependent on the neuronal expression of p75NTR. Importantly, cyclo-dPAKKR also significantly promoted the myelination of tropomyosin-related kinase receptor B-expressing neurons in vitro, whereas BDNF exerted a significant inhibitory effect. This indicated that while BDNF exerted a contrasting influence upon the myelination of distinct subsets of dorsal root ganglion (DRG) neurons in vitro, cyclo-dPAKKR uniformly promoted their myelination. Local injection of cyclo-dPAKKR adjacent to the developing sciatic nerve in vivo significantly enhanced myelin protein expression and significantly increased the number of myelinated axons. These results demonstrate that cyclo-dPAKKR promotes peripheral myelination in vitro and in vivo, suggesting it is a strategy worthy of further investigation for the treatment of peripheral demyelinating diseases.

Xiao J; Hughes RA; Lim JY; Wong AW; Ivanusic JJ; Ferner AH; Kilpatrick TJ; Murray SS

2013-05-01

135

N,N-diethyldithiocarbamate promotes oxidative stress prior to myelin structural changes and increases myelin copper content  

International Nuclear Information System (INIS)

Dithiocarbamates are a commercially important class of compounds that can produce peripheral neuropathy in humans and experimental animals. Previous studies have supported a requirement for copper accumulation and enhanced lipid peroxidation in dithiocarbamate-mediated myelinopathy. The study presented here extends previous investigations in two areas. Firstly, although total copper levels have been shown to increase within the nerve it has not been determined whether copper is increased within the myelin compartment, the primary site of lesion development. Therefore, the distribution of copper in sciatic nerve was characterized using synchrotron X-ray fluorescence microscopy to determine whether the neurotoxic dithiocarbamate, N,N-diethyldithiocarbamate, increases copper levels in myelin. Secondly, because lipid peroxidation is an ongoing process in normal nerve and the levels of lipid peroxidation products produced by dithiocarbamate exposure demonstrated an unusual cumulative dose response in previous studies the biological impact of dithiocarbamate-mediated lipid peroxidation was evaluated. Experiments were performed to determine whether dithiocarbamate-mediated lipid peroxidation products elicit an antioxidant response through measuring the protein expression levels of three enzymes, superoxide dismutase 1, heme oxygenase 1, and glutathione transferase ?, that are linked to the antioxidant response element promoter. To establish the potential of oxidative injury to contribute to myelin injury the temporal relationship of the antioxidant response to myelin injury was determined. Myelin structure in peripheral nerve was assessed using multi-exponential transverse relaxation measurements (MET2) as a function of exposure duration, and the temporal relationship of protein expression changes relative to the onset of changes in myelin integrity were determined. Initial assessments were also performed to explore the potential contribution of dithiocarbamate-mediated inhibition of proteasome function and inhibition of cuproenzyme activity to neurotoxicity, and also to assess the potential of dithiocarbamates to promote oxidative stress and injury within the central nervous system. These evaluations were performed using an established model for dithiocarbamate-mediated demyelination in the rat utilizing sciatic nerve, spinal cord and brain samples obtained from rats exposed to N,N-diethyldithiocarbamate (DEDC) by intra-abdominal pumps for periods of 2, 4, and 8 weeks and from non exposed controls. The data supported the ability of DEDC to increase copper within myelin and to enhance oxidative stress prior to structural changes detectable by MET2. Evidence was also obtained that the excess copper produced by DEDC in the central nervous system is redox active and promotes oxidative injury.

2009-08-15

136

Oligodendrocyte dynamics in the healthy adult CNS: evidence for myelin remodeling.  

UK PubMed Central (United Kingdom)

Oligodendrocyte precursors (OPs) continue to proliferate and generate myelinating oligodendrocytes (OLs) well into adulthood. It is not known whether adult-born OLs ensheath previously unmyelinated axons or remodel existing myelin. We quantified OP division and OL production in different regions of the adult mouse CNS including the 4-month-old optic nerve, in which practically all axons are already myelinated. Even there, all OPs were dividing and generating new OLs and myelin at a rate higher than can be explained by first-time myelination of naked axons. We conclude that adult-born OLs in the optic nerve are engaged in myelin remodeling, either replacing OLs that die in service or intercalating among existing myelin sheaths. The latter would predict that average internode length should decrease with age. Consistent with that, we found that adult-born OLs elaborated much shorter but many more internodes than OLs generated during early postnatal life.

Young KM; Psachoulia K; Tripathi RB; Dunn SJ; Cossell L; Attwell D; Tohyama K; Richardson WD

2013-03-01

137

Split-ball resonator  

CERN Multimedia

We introduce a new concept of split-ball resonator and demonstrate a strong omnidirectional magnetic dipole response for both gold and silver spherical plasmonic nanoparticles with nanometer-scale cuts. Tunability of the magnetic dipole resonance throughout the visible spectral range is demonstrated by a change of the depth and width of the nanoscale cut. We realize this novel concept experimentally by employing the laser-induced transfer method to produce near-perfect spheres and helium ion beam milling to make cuts with the nanometer resolution. Due to high quality of the spherical particle shape, governed by strong surface tension forces during the laser transfer process, and the clean, straight side walls of the cut made by helium ion milling, magnetic resonance is observed at 600 nm in gold and at 565 nm in silver nanoparticles. Structuring arbitrary features on the surface of ideal spherical resonators with nanoscale dimensions provides new ways of engineering hybrid resonant modes and ultra-high near-f...

Kuznetsov, Arseniy I; Fu, Yuan Hsing; Viswanathan, Vignesh; Rahmani, Mohsen; Valuckas, Vytautas; Kivshar, Yuri; Pickard, Daniel S; Lukiyanchuk, Boris

2013-01-01

138

Myelin protein transcripts increase in experimental diabetic neuropathy.  

UK PubMed Central (United Kingdom)

A Northern blot analysis of P0 and MBP myelin protein transcripts in the sciatic nerve from rats with alloxan-induced diabetes at two different time points is described. After 5 weeks of diabetes induction, only P0 mRNA is significantly increased by 39%, while at 14 weeks both P0 and MBP mRNA contents are markedly higher than controls. Insulin treatment normalizes glycemia levels, partially counteracts P0 mRNA increase at both stages of diabetes and delays MBP mRNA increase present only in chronic animals. We suggest that increased transcript levels of P0 and MBP in Schwann cells may represent a higher turnover of myelin sheath specific proteins in diabetic syndrome, as attempt to repair the hyperglycemia-induced nerve damage, which is partially prevented by insulin treatment.

Conti AM; Malosio ML; Scarpini E; Di Giulio AM; Scarlato G; Mantegazza P; Gorio A

1993-10-01

139

Vascularized peripheral nerve grafting promotes myelination of regrowing optic nerve.  

UK PubMed Central (United Kingdom)

We investigated whether the use of vascularized peripheral nerve grafts on the optic nerve stump enhances axonal regeneration of retinal ganglion cells compared with isolated nonvascularized grafts. The rat median nerve was microsurgically sutured with its supplying artery and vein to the optic nerve stump. The number of retinal ganglion cells with regenerating axons was evaluated by retrograde labeling into the grafted peripheral nerve, and the myelination of the regenerating axon fibers was examined by electron microscopy. The number of retinal ganglion cells with regenerating axons was significantly higher in the vascularized graft than in the nonvascularized graft. The ratio of myelinated axon fibers was also increased in vascularized grafts. Thus, grafting with their supplying arteries and veins to an injured nerve stump represents a promising strategy to accelerate axonal regeneration from neurons of the central nervous system.

Komatsu S; Wakabayashi T; Yamada K; Matsumoto K; Kimata Y; Kosaka J

2013-07-01

140

Myelin and traumatic brain injury: The copper deficiency hypothesis.  

UK PubMed Central (United Kingdom)

Nearly two million people suffer traumatic brain injury in the US each year. These injuries alter adversely the metabolism of myelin, a major lipid material in brain, both in people and in experimental injuries of animals. A newly discovered and severe human neuropathy from copper deficiency provides evidence that some people in the US are malnourished in copper. As it is well known among copper cognoscenti that it is impossible to synthesize myelin if copper nutriture is inadequate, it seems reasonable to assume that repair will be poor in this situation. Copper status of patients should be evaluated and experiments with injured animals should be repeated with graded doses of copper to determine if copper metabolism is important in this illness.

Klevay LM

2013-09-01

 
 
 
 
141

Postnatal development of rat peripheral nerves: an immunohistochemical study of membrane lipids common to non-myelin forming Schwann cells, myelin forming Schwann cells and oligodendrocytes.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Interest in the role of membrane lipids in Schwann cell function prompted this study of lipid antigens on myelin- and non-myelin forming Schwann cells. Using the monoclonal antibodies 07, which recognises galactocerebroside, 08, 09 and 011, the distribution and time course of expression of the 4 mem...

Eccleston, PA; Mirsky, R; Jessen, KR; Sommer, I; Schachner, M

142

Exploring the Role of Nerve Growth Factorin Multiple Sclerosis: Implications in Myelin Repair.  

UK PubMed Central (United Kingdom)

Multiple sclerosis (MS) is a chronic disease resulting from targeted destruction of central nervous system (CNS) myelin.MS is suggested to be an autoimmune disease involving the pathogenic activation of CD4+ T lymphocytesby a foreign antigen in the peripheral blood. The activated CD4+ T cellsliberate inflammatory cytokines that facilitate the breakdown of the blood-brain barrier promoting theirpassage into the CNS. Inside the CNS, CD4+ T cells become re-activated by myelin proteins sharing a similar structure to the foreign antigen that initially triggered the immune response. The CD4+ T cells continue to liberate inflammatory cytokines such as tumor necrosis factor a which activates macrophages and antibodies responsible for the phagocytosis of myelin.Acute CNS lesions can be re-myelinated, however, the repair of chronic demyelinating lesions is limited, leading to permanent neurological deficits. Although current MS treatments reduce severity and slow disease progression, they do not directly repair damaged myelin. Henceforth, recent treatment strategies have focused on neurotrophins such as nerve growth factor (NGF)for myelin repair. NGFpromotesaxonal regeneration, survival, protection and differentiation of oligodendrocytes and facilitatesmigration and proliferation of oligodendrocyte precursors to the sites of myelin damage. NGF also directly regulateskey structural proteins that comprise myelin. Interestingly, NGF also induces the production of brain-derived neurotrophic factor, another integral neurotrophin involved in myelination. The intricate signaling between neurotrophins and cytokines that governs myelin repair,supports the role of NGF as a leading therapeutic candidate in white matter disorders such as MS.

R Acosta CM; Cortes C; Macphee H; Namaka MP

2013-07-01

143

Plasma cell dyscrasia and peripheral neuropathy: identification of the myelin antigens that react with human paraproteins.  

UK PubMed Central (United Kingdom)

In some cases of polyneuropathy and plasma cell dyscrasia, the monclonal antibodies react with human peripheral nerve myelin. To identify the myelin antigens involved, we separated the proteins of human central and peripheral nerve myelin by polyacrylamide gel electrophoresis, transferred the proteins onto nitrocellulose sheets, and used an immunoenzymatic technique to detect the reactive antigens. Serum IgM but not IgG from three patients with neuropathy and complement-fixing anti-human myelin IgM paraproteins immunostained a protein of approximately 100,000 daltons in human peripheral nerve myelin and a protein or closely migrating proteins of similar size in human central nervous system myelin. In a fourth patient, both IgM and IgG immunostained the antigen. Immunostaining was specific for the paraprotein light chain type, and absorption of the patients' sera with human peripheral nerve myelin eliminated the reaction with the central nervous system proteins. No reaction was seen with rabbit peripheral nerve myelin or with membranes prepared from human myotubes, human T cells, or human fibroblasts. Control sera from six patients with neuropathy and IgM paraproteins that did not react with myelin, from four patients with IgM paraproteins but no neuropathy, and from three normal subjects did not immunostain myelin.

Latov N; Braun PE; Gross RB; Sherman WH; Penn AS; Chess L

1981-11-01

144

Organization of myelin in the mouse somatosensory barrel cortex and the effects of sensory deprivation.  

Science.gov (United States)

In rodents, the barrel cortex is a specialized area within the somatosensory cortex that processes signals from the mystacial whiskers. We investigated the normal development of myelination in the barrel cortex of mice, as well as the effects of sensory deprivation on this pattern. Deprivation was achieved by trimming the whiskers on one side of the face every other day from birth. In control mice, myelin was not present until postnatal day 14 and did not show prominence until postnatal day 30; adult levels of myelination were reached by the end of the second postnatal month. Unbiased stereology was used to estimate axon density in the interbarrel septal region and barrel walls as well as the barrel centers. Myelin was significantly more concentrated in the interbarrel septa/barrel walls than in the barrel centers in both control and sensory-deprived conditions. Sensory deprivation did not impact the onset of myelination but resulted in a significant decrease in myelinated axons in the barrel region and decreased the amount of myelin ensheathing each axon. Visualization of the oligodendrocyte nuclear marker Olig2 revealed a similar pattern of myelin as seen using histochemistry, but with no significant changes in Olig2+ nuclei following sensory deprivation. Consistent with the anatomical results showing less myelination, local field potentials revealed slower rise times following trimming. Our results suggest that myelination develops relatively late and can be influenced by sensory experience. PMID:23047707

Barrera, Kyrstle; Chu, Philip; Abramowitz, Jason; Steger, Robert; Ramos, Raddy L; Brumberg, Joshua C

2012-11-26

145

Organization of myelin in the mouse somatosensory barrel cortex and the effects of sensory deprivation.  

UK PubMed Central (United Kingdom)

In rodents, the barrel cortex is a specialized area within the somatosensory cortex that processes signals from the mystacial whiskers. We investigated the normal development of myelination in the barrel cortex of mice, as well as the effects of sensory deprivation on this pattern. Deprivation was achieved by trimming the whiskers on one side of the face every other day from birth. In control mice, myelin was not present until postnatal day 14 and did not show prominence until postnatal day 30; adult levels of myelination were reached by the end of the second postnatal month. Unbiased stereology was used to estimate axon density in the interbarrel septal region and barrel walls as well as the barrel centers. Myelin was significantly more concentrated in the interbarrel septa/barrel walls than in the barrel centers in both control and sensory-deprived conditions. Sensory deprivation did not impact the onset of myelination but resulted in a significant decrease in myelinated axons in the barrel region and decreased the amount of myelin ensheathing each axon. Visualization of the oligodendrocyte nuclear marker Olig2 revealed a similar pattern of myelin as seen using histochemistry, but with no significant changes in Olig2+ nuclei following sensory deprivation. Consistent with the anatomical results showing less myelination, local field potentials revealed slower rise times following trimming. Our results suggest that myelination develops relatively late and can be influenced by sensory experience.

Barrera K; Chu P; Abramowitz J; Steger R; Ramos RL; Brumberg JC

2013-04-01

146

Chondroitin sulfate proteoglycans inhibit oligodendrocyte myelination through PTP?.  

UK PubMed Central (United Kingdom)

CNS damage often results in demyelination of spared axons due to oligodendroglial cell death and dysfunction near the injury site. Although new oligodendroglia are generated following CNS injury and disease, the process of remyelination is typically incomplete resulting in long-term functional deficits. Chondroitin sulfate proteoglycans (CSPGs) are upregulated in CNS grey and white matter following injury and disease and are a major component of the inhibitory scar that suppresses axon regeneration. CSPG inhibition of axonal regeneration is mediated, at least in part, by the protein tyrosine phosphatase sigma (PTP?) receptor. Recent evidence demonstrates that CSPGs inhibit OL process outgrowth, however, the means by which their effects are mediated remains unclear. Here we investigate the role of PTP? in CSPG inhibition of OL function. We found that the CSPGs, aggrecan, neurocan and NG2 all imposed an inhibitory effect on OL process outgrowth and myelination. These inhibitory effects were reversed by degradation of CSPGs with Chondroitinase ABC prior to OL exposure. RNAi-mediated down-regulation of PTP? reversed the inhibitory effect of CSPGs on OL process outgrowth and myelination. Likewise, CSPG inhibition of process outgrowth and myelination was significantly reduced in cultures containing PTP?(-/-) OLs. Finally, inhibition of Rho-associated kinase (ROCK) increased OL process outgrowth and myelination during exposure to CSPGs. These results suggest that in addition to their inhibitory effects on axon regeneration, CSPGs have multiple inhibitory actions on OLs that result in incomplete remyelination following CNS injury. The identification of PTP? as a receptor for CSPGs, and the participation of ROCK downstream of CSPG exposure, reveal potential therapeutic targets to enhance white matter repair in the damaged CNS.

Pendleton JC; Shamblott MJ; Gary DS; Belegu V; Hurtado A; Malone ML; McDonald JW

2013-09-01

147

[Characteristics of myelin basic protein from dog spinal cord  

UK PubMed Central (United Kingdom)

Some characteristics of the myelin basic protein from dog spinal cord were studied. The basic protein has a molecular weight of 18,000; the isoelectric point is 9.5. The amino acid composition of the protein was determined. Electrophoresis in 15% polyacrylamide gel revealed the heterogeneity of the basic protein. The EAE-activity of the basic protein was tested on guinea pigs.

Mendzheritski? AM; Vovchenko IB; Sherstnev KB

1979-01-01

148

Tcf7l2 is tightly controlled during myelin formation.  

UK PubMed Central (United Kingdom)

Recent, studies have shown that Tcf7l2, an important transcription factor in Wnt pathway, plays critical roles in oligodendrocyte development. In this article we report a study showing that Tcf7l2 is under tight regulation during myelin formation. We have found that during early development, Tcf7l2 mRNA appears much earlier than the protein, suggesting a regulation at the translational level. We induced demyelination in a mouse model by a dietary toxin, where remyelination followed after a few weeks, and found that Tcf7l2 protein was expressed specifically during the active remyelination phase. Similarly, in human patients with demyelination diseases, Tcf7l2 protein expression was specifically promoted in regions undergoing active remyelination. During remyelination, Tcf7l2 was only expressed in non-dividing oligodendrocyte precursors and was associated with modest levels of nuclear beta-catenin. We also documented that Tcf7l2 could form protein complex with Olig2, but not with Olig1. Our data showed that during myelin formation, Tcf7l2/beta-catenin is regulated temporally, spatially, and also at levels of expression. These data suggest a key role for Tcf7l2 in myelination/remyelination processes via a tightly controlled activation of Wnt/beta-catenin pathway and the interaction with Olig2.

Fu H; Kesari S; Cai J

2012-04-01

149

Kinetics of entry P0 protein into peripheral nerve myelin  

Energy Technology Data Exchange (ETDEWEB)

Sciatic nerves from 9-day-old rat pups were removed, sliced into 0.4-mm sections, and incubated with (/sup 3/H)fucose or (/sup 14/)glycine precursors. The nerve slices system gave nearly linear incorporation of (/sup 3/H)fucose as a function of time for 3 h, after an initial lag of approximately 30 min for homogenate and approximately 60 min for myelin. Incorporation of (3H)fucose at constant specific radioactivity was directly proportional to exogenous fucose levels over the range 3.0 x 10(-8) M to 1.5 x 10(-6) M. Analysis of labeled proteins by sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that greater than 50% of labeled glycoprotein was P0, with no other major constituents. This system was used in fucose-chase experiments to determine that a period of approximately 20 min elapses between fucosylation and assembly of P0 into myelin. Cycloheximide inhibition of protein synthesis was used to determine that a period of approximately 33 min elapses between protein synthesis and appearance of P0 myelin.

Rapaport, R.N.; Benjamins, J.A.

1981-07-01

150

Proliferation of Schwann cells induced by axolemmal and myelin membranes  

Energy Technology Data Exchange (ETDEWEB)

Purified Schwann Cells were cultured from neonatal rat sciatic nerve using a modification of the method of Brockes. Schwann cells and contaminating fibroblasts were unambiguously identified using fluorescent antibodies of 2'3' cyclic nucleotide 3'-phosphodiesterase and the thy 1.1 antigen respectively. The Schwann cells were quiescent unless challenged with mitogens. They proliferated rapidly in response to the soluble mitogen, cholera toxin, or to membrane fractions from rat CNS or PNS, prepared by the method of DeVries. Mitogenic activity was present in both axolemmal and myelin enriched fractions and promoted a 10-15 fold increase in the rate of /sup 3/H-thymidine uptake. The axolemmal mitogen was sensitive to heat (80/sup 0/C for 10 minutes), trypsin digestion (0.05% x 30 mins) or to treatment with endoglycosidase D, suggesting that it could be a glycoprotein. Fifty percent of the axolemmal mitogenic activity was solubilized in 1% octyl-glucoside. The solubilized material, however, was very unstable and further purification was not possible. The myelin associated mitogenic activity was markedly different. It was resistant to freeze thaw cycles, trypsin digestion of endoglycosidase treatment and the activity was actually enhanced by heating at 100/sup 0/C for two hours. It is proposed that the axolemmal activity is responsible for Schwann cell proliferation during development and that the myelin associated activity promotes Schwann cell proliferation during Wallerian degeneration.

Dinneen, M..

1985-01-01

151

Proliferation of Schwann cells induced by axolemmal and myelin membranes  

International Nuclear Information System (INIS)

Purified Schwann Cells were cultured from neonatal rat sciatic nerve using a modification of the method of Brockes. Schwann cells and contaminating fibroblasts were unambiguously identified using fluorescent antibodies of 2'3' cyclic nucleotide 3'-phosphodiesterase and the thy 1.1 antigen respectively. The Schwann cells were quiescent unless challenged with mitogens. They proliferated rapidly in response to the soluble mitogen, cholera toxin, or to membrane fractions from rat CNS or PNS, prepared by the method of DeVries. Mitogenic activity was present in both axolemmal and myelin enriched fractions and promoted a 10-15 fold increase in the rate of 3H-thymidine uptake. The axolemmal mitogen was sensitive to heat (800C for 10 minutes), trypsin digestion (0.05% x 30 mins) or to treatment with endoglycosidase D, suggesting that it could be a glycoprotein. Fifty percent of the axolemmal mitogenic activity was solubilized in 1% octyl-glucoside. The solubilized material, however, was very unstable and further purification was not possible. The myelin associated mitogenic activity was markedly different. It was resistant to freeze thaw cycles, trypsin digestion of endoglycosidase treatment and the activity was actually enhanced by heating at 1000C for two hours. It is proposed that the axolemmal activity is responsible for Schwann cell proliferation during development and that the myelin associated activity promotes Schwann cell proliferation during Wallerian degeneration.

1985-01-01

152

Myelin-associated changes in mouse brain following irradiation  

International Nuclear Information System (INIS)

The goals of this study were to quantify myelin-associated changes in the brain following single doses of radiation and to determine their relationship to the dose limits that this tissue can tolerate. Mice developed a transient loss of balance 1 month after 60 Gy doses 250 kVp X-rays to the brain and 3-4 months after 30-45 Gy radiation, but not after lower doses. The symptoms were transient and lasted ? 1 month. The ED50/300 for radiation-induced brain death, which occurred largely between 200 and 240 days, was 32.4 Gy (29.1, 35.5 Gy, 95% confidence limit of mean). At the time that animals developed neurological symptoms, 3-4 months after irradiation with doses of 30-45 Gy, biochemical assays of myelin-associated proteins showed decreases in 2',3' -cyclic nucleotide phosphohydrolase (CNPase) and myelin basic protein (MBP) levels that were not seen with lower radiation doses. By 120-180 days, further dose-dependent decreases in both CNPase and MBP levels were found after 20-45 Gy irradiation that preceded and correlated with death. The correlation of the decrease in CNPase and MBP levels with the incidence of transient neurological malfunction and animal death, together with histological evidence, suggests that demyelination is responsible for these phenomena. (author).

1993-01-01

153

Myelin-associated changes in mouse brain following irradiation.  

UK PubMed Central (United Kingdom)

The goals of this study were to quantify myelin-associated changes in the brain following single doses of radiation and to determine their relationship to the dose limits that this tissue can tolerate. Mice developed a transient loss of balance 1 month after 60 Gy doses 250 kVp X-rays to the brain and 3-4 months after 30-45 Gy radiation, but not after lower doses. The symptoms were transient and lasted approximately 1 month. The ED50/300 for radiation-induced brain death, which occurred large between 200 and 240 days, was 32.4 Gy (29.1, 35.5 Gy, 95% confidence limit of mean). At the time that animals developed neurological symptoms, 3-4 months after irradiation with doses of 30-45 Gy, biochemical assays of myelin-associated proteins showed decreases in 2',3'-cyclic nucleotide phosphohydrolase (CNPase) and myelin basic protein (MBP) levels that were not seen with lower radiation doses. By 120-180 days, further dose-dependent decreases in both CNPase and MBP levels were found after 20-45 Gy irradiation that preceded and correlated with death. The correlation of the decrease in CNPase and MBP levels with the incidence of transient neurological malfunction and animal death, together with histological evidence, suggests that demyelination is responsible for these phenomena.

Chiang CS; McBride WH; Withers HR

1993-06-01

154

Mycobacterium leprae binds to a major human peripheral nerve glycoprotein myelin P zero (P0).  

Science.gov (United States)

We have previously shown that a major phosphorylated 25-kDa glycoprotein of the human peripheral nerve binds to Mycobacterium leprae. In the present study, we confirm that the 25-kDa glycoprotein of the human peripheral nerve is myelin P zero (P0) by immunoprecipitation and Western blot experiments using monoclonal antibodies to myelin P0. Immunohistochemical studies on human nerve using these antibodies to myelin P0 exhibited a strong immunoreactivity to the myelin and Schwann cells. Myelin P0 is a peripheral nerve specific protein; therefore it could likely be one of the key target molecules for M. leprae binding/internalization or even contact-dependent demyelination. This finding of M. leprae binding to myelin P0 adds to the present understanding on neural predilection of M. leprae. PMID:12945534

Suneetha, Lavanya M; Singh, Surya S; Vani, Meher; Vardhini, Deena; Scollard, David; Archelos, Juan J; Srinivasulu, M; Suneetha, Sujai

2003-09-01

155

Effect of benzene and lead on relationship between. delta. -aminolevulinic acid and brain myelin proteins  

Energy Technology Data Exchange (ETDEWEB)

The aim of this investigation was to study binding of ALA by brain myelin under normal conditions and under the influence of lead and benzene. Rabbits of three different groups were given an intercranial injection of /sup 14/C-ALA (50 microCi) in physiological saline in a volume of 0.25 ml. The myelin fraction was obtained by differential centrifugation and the /sup 14/C-ALA in it was assayed on an LKB liquid scintillation counter. By determining the quantity of exogenous /sup 14/C-ALA bound with myelin, the authors found that myelin of white matter in the brain contains more of the acid than myelin of the gray matter. Data on binding of /sup 14/C-ALA calculated per milligram of each group of myelin proteins isolated is given.

Muzyka, V.I.; Bogovskii, L.A.

1986-03-01

156

[Proteolipids of brain myelin and synaptosomes in the frog and hen  

UK PubMed Central (United Kingdom)

Proteolipid complex of Folch-Lees has been obtained and purified from the myelin and synaptosomes of the brain of the frog Rana temporaria and hen Gallus domesticus. Relative content of this proteolipid and glycolipids in the myelin is almost twice higher, whereas that of phospholipids--1 1/2 times lower than in the synaptosomal membranes of the same animal. Protein content of this complex is higher for myelin than for synaptosomal membranes; opposite relation was found with respect to phospholipid content. Within this complex, lipids are presented mainly by phospholipids, especially by acid ones which amount to 30-60%. Proteolipid complexes fro the myelin and synaptosomes differ from each other by their lipid component. Myelin proteolipid complex contains mainly phosphatidylserine and phosphatid acid, whereas synaptosomal one--phosphatidylserine and diphosphatediglycerol. No significant differences were found in fatty acid composition of phospholipids from proteolipid complex from myelin and synaptosomes as compared to this composition in the initial membranes.

Denisova NA; Zabelinski? SA

1986-07-01

157

Signals regulating myelination in peripheral nerves and the Schwann cell response to injury.  

UK PubMed Central (United Kingdom)

In peripheral nerves, Schwann cells form myelin, which facilitates the rapid conduction of action potentials along axons in the vertebrate nervous system. Myelinating Schwann cells are derived from neural crest progenitors in a step-wise process that is regulated by extracellular signals and transcription factors. In addition to forming the myelin sheath, Schwann cells orchestrate much of the regenerative response that occurs after injury to peripheral nerves. In response to injury, myelinating Schwann cells dedifferentiate into repair cells that are essential for axonal regeneration, and then redifferentiate into myelinating Schwann cells to restore nerve function. Although this remarkable plasticity has long been recognized, many questions remain unanswered regarding the signaling pathways regulating both myelination and the Schwann cell response to injury.

Glenn TD; Talbot WS

2013-07-01

158

Excitation block in a nerve fibre model owing to potassium-dependent changes in myelin resistance  

DEFF Research Database (Denmark)

The myelinated nerve fibre is formed by an axon and Schwann cells or oligodendrocytes that sheath the axon by winding around it in tight myelin layers. Repetitive stimulation of a fibre is known to result in accumulation of extracellular potassium ions, especially between the axon and the myelin. Uptake of potassium leads to Schwann cell swelling and myelin restructuring that impacts the electrical properties of the myelin. In order to further understand the dynamic interaction that takes place between the myelin and the axon, we have modelled submyelin potassium accumulation and related changes in myelin resistance during prolonged high-frequency stimulation. We predict that potassium-mediated decrease in myelin resistance leads to a functional excitation block with various patterns of altered spike trains. The patterns are found to depend on stimulation frequency and amplitude and to range from no block (less than 100 Hz) to a complete block (greater than 500 Hz). The transitional patterns include intermittent periodic block with interleaved spiking and non-spiking intervals of different relative duration as well as an unstable regime with chaotic switching between the spiking and non-spiking states. Intermittent conduction blocks are accompanied by oscillations of extracellular potassium. The mechanism of conductance block based on myelin restructuring complements the already known and modelled block via hyperpolarization mediated by the axonal sodium pump and potassium depolarization.

Brazhe, A.R.; Maksimov, G.V.

2011-01-01

159

Excitation block in a nerve fibre model owing to potassium-dependent changes in myelin resistance.  

Science.gov (United States)

The myelinated nerve fibre is formed by an axon and Schwann cells or oligodendrocytes that sheath the axon by winding around it in tight myelin layers. Repetitive stimulation of a fibre is known to result in accumulation of extracellular potassium ions, especially between the axon and the myelin. Uptake of potassium leads to Schwann cell swelling and myelin restructuring that impacts the electrical properties of the myelin. In order to further understand the dynamic interaction that takes place between the myelin and the axon, we have modelled submyelin potassium accumulation and related changes in myelin resistance during prolonged high-frequency stimulation. We predict that potassium-mediated decrease in myelin resistance leads to a functional excitation block with various patterns of altered spike trains. The patterns are found to depend on stimulation frequency and amplitude and to range from no block (less than 100 Hz) to a complete block (greater than 500 Hz). The transitional patterns include intermittent periodic block with interleaved spiking and non-spiking intervals of different relative duration as well as an unstable regime with chaotic switching between the spiking and non-spiking states. Intermittent conduction blocks are accompanied by oscillations of extracellular potassium. The mechanism of conductance block based on myelin restructuring complements the already known and modelled block via hyperpolarization mediated by the axonal sodium pump and potassium depolarization. PMID:22419976

Brazhe, A R; Maksimov, G V; Mosekilde, E; Sosnovtseva, O V

2010-12-01

160

Excitation block in a nerve fibre model owing to potassium-dependent changes in myelin resistance.  

UK PubMed Central (United Kingdom)

The myelinated nerve fibre is formed by an axon and Schwann cells or oligodendrocytes that sheath the axon by winding around it in tight myelin layers. Repetitive stimulation of a fibre is known to result in accumulation of extracellular potassium ions, especially between the axon and the myelin. Uptake of potassium leads to Schwann cell swelling and myelin restructuring that impacts the electrical properties of the myelin. In order to further understand the dynamic interaction that takes place between the myelin and the axon, we have modelled submyelin potassium accumulation and related changes in myelin resistance during prolonged high-frequency stimulation. We predict that potassium-mediated decrease in myelin resistance leads to a functional excitation block with various patterns of altered spike trains. The patterns are found to depend on stimulation frequency and amplitude and to range from no block (less than 100 Hz) to a complete block (greater than 500 Hz). The transitional patterns include intermittent periodic block with interleaved spiking and non-spiking intervals of different relative duration as well as an unstable regime with chaotic switching between the spiking and non-spiking states. Intermittent conduction blocks are accompanied by oscillations of extracellular potassium. The mechanism of conductance block based on myelin restructuring complements the already known and modelled block via hyperpolarization mediated by the axonal sodium pump and potassium depolarization.

Brazhe AR; Maksimov GV; Mosekilde E; Sosnovtseva OV

2011-02-01

 
 
 
 
161

[Interrelation of delta-aminolevulinic acid and brain myelin proteins as affected by benzene and lead  

UK PubMed Central (United Kingdom)

An experimental model of subacute lead and benzene intoxication was induced in rabbits. It increased significantly delta-aminolevulinic acid (14C-ALA) incorporation into CNS myelin. ALA stably fixes on myelin proteins, especially Wolfgram proteins. In spite of this about one half of ALA incorporated into myelin linked with its basic proteins. Lead and benzene intoxication cause changes in the proportion of the basic fractions of myelin proteins. The amount of basic proteins increases, while the amount of proteolipid and Wolfgram proteins decreases. Lead and especially benzene intoxication decreases exogenous ALA insertion into basic proteins and proteolipid proteins, with ALA fixation on Wolfgram proteins remaining unchanged.

Muzyka VI; Bogovski? LA

1985-10-01

162

[A case of loss of retinal myelinated nerve fibers in a chronic glaucoma].  

UK PubMed Central (United Kingdom)

PURPOSE/METHOD: A female patient underwent retinographic control and presented a pattern of myelinated nerve fibers in both eyes. Two years later, patient underwent a second retinographic control showing 10/10 glaucomatous cupping in her right eye. This was associated to loss of myelinated nerve fibers. RESULTS/CONCLUSIONS: Etiology, characteristics, associations and other causes of loss of myelinated retinal nerve fibers in chronic glaucoma are reviewed. This is the second of two photograph documented cases where loss of myelinated nerve fibers is associated to an open angle primary glaucoma.

López Sánchez E; Marín Montiel J; Francés Muńoz E; Menezo Rozalén JL

2002-01-01

163

Ultrastructural Changes in the Myelinated Nerve Fibers of the Sciatic Nerve in Galactose Intoxication in Rats  

Directory of Open Access Journals (Sweden)

Full Text Available The objectives were to study the ultrastructural changes in the myelinated nerve fibers in an animal model of galactosaemia. The study was done in the Anatomy Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia. Twenty-four adult male albino rats were used (6 control and 12 experimental animals). Galactosaemia was induced by adding 40% D-galactose to the rats' diet for 2 months. Sciatic nerves of the control and experimental animals were removed and processed for electron microscopic study. Four months following galactosaemia, the myelinated nerve fibers showed cytoplasmic vacuoles in Schwann cells, myelin degeneration, axonal retraction and destruction of the myelinated axons. 6 months after induction, some myelinated nerve fibers showed disruption of myelin sheaths with marked shrinkage of the axons. The endoneurial edema was prominent and some regenerating nerve fibers were reported. 8 months latter: the endoneurial and intra-axonal oedema accumulated more. Schwann cells showed cytoplasmic degenerated myelin, fat vacuoles and accumulation of fine glycogen granules in the axoplasm. It could be concluded that in galactose intoxication induced degenerative changes in the myelinated nerve fibers. It showed also decrease in diameters of the myelinated nerve fibers and axons.

Faris M. Altaf

2012-01-01

164

X-ray studies on the bilayer structure of trypsin-treated rat brain myelin  

International Nuclear Information System (INIS)

Trypsin-treated rat brain myelin was subjected to biochemical and x-ray studies. Untreated myelin gave rise to a pattern of three rings with a fundamental repeat period of 155 A consisting of two bilayers per repeat period, whereas myelin treated with trypsin showed a fundamental repeat period of 75 A with one bilayer per repeat period. The integrated raw intensity of the h = 4 reflection with respect to the h = 2 reflection is 0.38 for untreated myelin. The corresponding value reduced to 0.23, 0.18, 0.17 for myelin treated with 5, 10, 40 units of trypsin per mg of myelin, respectively, for 30 min at 30 degC. The decrease in relative raw intensity of the higher-order reflection relative to the lower-order reflection is suggestive of a disordering of the phosphate groups upon trypsin treatment or an increased mosaicity of the membrane or a combination of both these effects. However, trypsin treatment does not lead to a complete breakdown of the membrane. The integrated intensity of the h = 1 reflection, though weak, is above the measurable threshold for untreated myelin, whereas the corresponding intensity is below the measurable threshold for trypsin-treated myelin, indicating a possible asymmetric to symmetric transition of the myelin bilayer structure about its centre after trypsin treatment. (author). 24 refs., 4 figs., 1 tab.

1995-01-01

165

[Peripheral nerve myelin antigen-specific T cells in human  

UK PubMed Central (United Kingdom)

In recent years, anti-myelin glycolipid antibodies have been reported to be specific for acute inflammatory demyelinating polyneuritis (AIDP) so the involvement of autoimmune mechanism by such autoantibodies was strongly suggested as a cause of AIDP. However, the cellular immunity of AIDP has been seldom reported yet. To examine the T cell response to peripheral nerve antigens in human, we tried to establish T cell lines reactive to peripheral myelin antigens. P0 56-71, P0 180-199 and P2 59-78 peptides from human peripheral blood of controls and patients with inflammatory demyelinating polyneuritis. Frequencies of T cells reactive with P0 56-71, P0 180-199 and P2 59-78 peptides in five controls were (0.59 +/- 0.81) x 10(-7), (1.53 +/- 0.53) x 10(-7) and (0.11 +/- 0.24) x 10(-7), respectively. Frequency of P0 180-199-reactive T cells in one AIDP patient of acute stage was 3.5 x 10(-7) and approximately 2 times high value of controls. There is no significant association between their frequency and specific MHC class II genotypes in subjects until now. Thus, peripheral myelin antigen-specific T cell lines in particular recognizing P0 180-199 were established from the majority of controls and polyneuritis patients. These results suggest that the residues of P0 180-199 might be one of T cell epitopes also in human subjects.

Ota K; Shimizu Y; Ueda M; Akiyama N; Iwata M

1996-07-01

166

Effects of an enriched environment on myelin sheaths in the white matter of rats during normal aging: A stereological study.  

UK PubMed Central (United Kingdom)

We found that an enriched environment (EE) could delay the loss of myelinated fibers in the white matter of rats during normal aging. However, the reasons for the protective effects of EE on the myelinated fibers were unclear. In this present study, via the use of stereological methods, we quantitatively investigated the myelin sheaths and the axons of myelinated fibers in the white matter of rats reared in an EE or a standard environment (SE) during the aging process. The results showed that an EE induced significant increases in the lengths of myelinated fibers, the axon volumes and the myelin sheath volumes of aging rats when compared with SE rats and that the enrichment effects, with the exception of the axon volumes, were sex- and age-independent. The mean diameter of the myelinated fibers, the mean perimeter of the myelin sheaths and the mean thicknesses of the myelin sheaths were not significantly changed. The EE-induced increase in myelinated fibers was mostly observed in those of smaller diameter (<1?m) with thinner myelin sheaths (<0.16?m), which had an optimal axon-fiber ratio (g=0.61). Our results suggest that EE-induced an increase in myelinated fibers in the white matter of aging rats primarily due to marked remyelination and some ongoing myelination.

Yang S; Li C; Qiu X; Zhang L; Lu W; Chen L; Zhao YY; Shi XY; Huang CX; Cheng GH; Tang Y

2013-03-01

167

Longitudinal PET imaging for monitoring myelin repair in the spinal cord.  

UK PubMed Central (United Kingdom)

Objective: Novel therapeutic interventions aimed at myelin repair are now under development for neuroprotection as well as functional recovery of patients with multiple sclerosis (MS). However, development of myelin-repair therapy necessitates a non-invasive approach for measuring changes in myelin content in vivo in a quantitative fashion not yet possible using MRI. For this reason, we developed a novel PET probe, termed [(11) C]MeDAS, that is capable of longitudinally imaging CNS myelin content. Methods: The binding properties of [(11) C]MeDAS for myelin were systematically evaluated by in vitro and in situ fluorescent staining of the spinal cord and the brain, and by in vivo competitive blocking studies. Longitudinal PET studies were conducted in three rat models involving acute focal neuroinflammation in the brain, LPC-induced focal demyelination in the spinal cord, and experimental autoimmune encephalomyelitis (EAE). Image-guided myelin repair therapy was conducted in an LPC rat model using a mesenchymal stem cell-based hepatocyte growth factor (HGF). Biodistribution and acute toxicity studies of [(11) C]MeDAS were also conducted. Results: MeDAS selectively stains myelin in the spinal cord and brain. Neuroinflammation did not affect [(11) C]MeDAS uptake in the brain as long as the myelin sheaths remained intact. Longitudinal PET studies in LPC and EAE rat models demonstrate that [(11) C]MeDAS uptake changes correlate with associated myelin loss in the spinal cord. Furthermore, using [(11) C]MeDAS-PET, the efficacy of myelin-repair therapy with HGF was longitudinally monitored in vivo. Interpretations: [(11) C]MeDAS-PET is a promising imaging marker for monitoring myelin pathology in vivo, future applications of which in humans should be achievable. ANN NEUROL 2013. © 2013 American Neurological Association.

Wu C; Zhu J; Baeslack J; Zaremba A; Hecker J; Kraso J; Matthews PM; Miller RH; Wang Y

2013-07-01

168

[Hypnogenic effect of antibodies to myelin basic protein administered intraventricularly  

UK PubMed Central (United Kingdom)

Intraventricular administration of myelin basic protein amtibodies in rabbits evoked high-amplitude slow waves in the ECoG, the animal takes a characteristic sleep posture, muscular tension weakens, the nictitating membrane lowers down, and the respiratory rhythm becomes stable. Spontaneous activity and arousal as well as recruiting responses induced by electrical stimulation of the thalamic CM in the cortical and thalamic structures suggest that the state resulting from the anti-BP antibodies administration is similar to slow wave sleep. The effect of anti-BP antibodies administration seems to be due to direct influence upon synaptic events in the thalamic "sleep-inducing" structures.

Burikov AA; Mendzheritski? AM

1982-07-01

169

[Myelin basic protein in cerebrospinal fluid in neurocysticercosis  

UK PubMed Central (United Kingdom)

Cerebrospinal fluid (CSF) from 115 patients with several neurological disorders were tested for the presence of myelin basic protein (MBP), fragment P1 43-88. Cases were divided into groups according to neurological diagnosis. The control group (50 patients with chronic headache) presented normal CSF composition and presented no evidence of the presence of MBP. MBP was found in: four cases of the 44 of neurocysticercosis; three of the 8 cases of multiple sclerosis; one case of schistosomiasis with spinal cord involvement. Neuroimmunological data are discussed considering results found in this investigation.

Livramento JA; Machado LR; Whitaker JN; Spina-Franca A

1985-06-01

170

Angular Distributions of Higher Order Splitting Functions  

CERN Multimedia

We study the angular distributions of the splitting functions for processes for which a parton splits into three partons. Unlike the case of coherent branching, we find that both in vacuum and in the presence of the dense QCD matter, such collinear splitting functions are neither ordered, nor anti-ordered. In the medium-induced splitting functions the angular distributions are broader compared to the similar vacuum distribution, a feature previously noticed from the lowest order medium-induced splitting functions.

Ovanesyan, Grigory

2013-01-01

171

Lattice splitting under intermittent flows  

CERN Multimedia

We study the splitting of regular square lattices subject to stochastic intermittent flows. By extensive Monte Carlo simulations we reveal how the time span until the occurence of a splitting depends on various flow patterns imposed on the lattices. Increasing the flow fluctuation frequencies shortens this time span which reaches a minimum before rising again due to inertia effects incorporated in the model. The size of the largest connected component after the splitting is rather independent of the flow fluctuations but sligthly decreases with the link capacities. Our results are relevant for assessing the robustness of real-life systems, such as electric power grids with a large share of renewable energy sources including wind turbines and photovoltaic systems.

Schläpfer, Markus

2010-01-01

172

Level splitting at macroscopic scale.  

UK PubMed Central (United Kingdom)

A walker is a classical self-propelled wave particle association moving on a fluid interface. Two walkers can interact via their waves and form orbiting bound states with quantized diameters. Here we probe the behavior of these bound states when setting the underlying bath in rotation. We show that the bound states are driven by the wave interaction between the walkers and we observe a level splitting at macroscopic scale induced by the rotation. Using the analogy between Coriolis and Lorentz forces, we show that this effect is the classical equivalent to Zeeman splitting of atomic energy levels.

Eddi A; Moukhtar J; Perrard S; Fort E; Couder Y

2012-06-01

173

Split ring containment attachment device  

Energy Technology Data Exchange (ETDEWEB)

A containment attachment device 10 for operatively connecting a glovebag 200 to plastic sheeting 100 covering hazardous material. The device 10 includes an inner split ring member 20 connected on one end 22 to a middle ring member 30 wherein the free end 21 of the split ring member 20 is inserted through a slit 101 in the plastic sheeting 100 to captively engage a generally circular portion of the plastic sheeting 100. A collar potion 41 having an outer ring portion 42 is provided with fastening means 51 for securing the device 10 together wherein the glovebag 200 is operatively connected to the collar portion 41.

Sammel, Alfred G. (Pittsburgh, PA)

1996-01-01

174

Hyperfine splitting in lithiumlike bismuth  

Energy Technology Data Exchange (ETDEWEB)

Uncertainties involving the distribution of nuclear magnetism that affect the interpretation of ground-state hyperfine splitting (hfs) in hydrogenlike ions can be avoided by also measuring hyperfine splitting in lithiumlike ions. Because a recent experiment looking for hfs in lithiumlike bismuth at the predicted value of 0.7971(2) eV had negative results, we have repeated the calculation using a QED approach based on both screened potentials and the Coulomb potential. We find 0.79715(13) eV, in good agreement with the previous calculation.

Sapirstein, J.; Cheng, K. T.

2001-03-01

175

Biphasic water splitting by osmocene.  

UK PubMed Central (United Kingdom)

The photochemical reactivity of osmocene in a biphasic water-organic solvent system has been investigated to probe its water splitting properties. The photoreduction of aqueous protons to hydrogen under anaerobic conditions induced by osmocene dissolved in 1,2-dichloroethane and the subsequent water splitting by the osmocenium metal-metal dimer formed during H(2) production were studied by electrochemical methods, UV-visible spectrometry, gas chromatography, and nuclear magnetic resonance spectroscopy. Density functional theory computations were used to validate the reaction pathways.

Ge P; Todorova TK; Patir IH; Olaya AJ; Vrubel H; Mendez M; Hu X; Corminboeuf C; Girault HH

2012-07-01

176

Abnormal protein and lipid compositions of the cerebral myelin of a patient with maple syrup urine disease.  

UK PubMed Central (United Kingdom)

Biochemical analyses were performed on the myelin isolated from the brain tissue of a patient with maple syrup urine disease. He was mostly treated by dietary management from day 8 after his birth until he died at 4 years and 5 months of age. It was found that the myelin contained major proteolipid-protein and high molecular weight protein and a very minor basic protein. The lipid composition of the myelin showed a marked decrease in phosphatidylethanolamine, but there was no remarkable reduction of cerebroside and sulfatide as well as other phospholipids in the myelin. Although the ganglioside composition of the myelin indicated that GM1 was a major ganglioside just like in the normal myelin, the myelin had an abnormal composition of an higher proportion of GD3 and a lower proportion of GM4, GD1b and GT1b. However, overall fatty acid compositions of the myelin lipids seemed rather normal.

Taketomi T; Kunishita T; Hara A; Mizushima S

1983-04-01

177

A developmentally regulated DNA-binding protein from mouse brain stimulates myelin basic protein gene expression.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Transcription of the myelin basic protein (MBP) gene is regulated in a cell-type-specific and developmental stage-specific manner during myelin formation in the murine central nervous system. The 5'-flanking region of the MBP gene contains several regulatory elements that differentially contribute t...

Haas, S; Gordon, J; Khalili, K

178

DDIT4/REDD1/RTP801 Is a Novel Negative Regulator of Schwann Cell Myelination.  

UK PubMed Central (United Kingdom)

Signals that promote myelination must be tightly modulated to adjust myelin thickness to the axonal diameter. In the peripheral nervous system, axonal neuregulin 1 type III promotes myelination by activating erbB2/B3 receptors and the PI3K/AKT/mTOR pathway in Schwann cells. Conversely, PTEN (phosphatase and tensin homolog on chromosome 10) dephosphorylates PtdIns(3,4,5)P3 and negatively regulates the AKT pathway and myelination. Recently, the DLG1/SAP97 scaffolding protein was described to interact with PTEN to enhance PIP3 dephosphorylation. Here we now report that nerves from mice with conditional inactivation of Dlg1 in Schwann cells display only a transient increase in myelin thickness during development, suggesting that DLG1 is a transient negative regulator of myelination. Instead, we identified DDIT4/RTP801/REDD1 as a sustained negative modulator of myelination. We show that DDIT4 is expressed in Schwann cells and its maximum expression level precedes the peak of AKT activation and of DLG1 activity in peripheral nerves. Moreover, loss of DDIT4 expression both in vitro and in vivo in Ddit4-null mice provokes sustained hypermyelination and enhanced mTORC1 activation, thus suggesting that this molecule is a novel negative regulator of PNS myelination.

Noseda R; Belin S; Piguet F; Vaccari I; Scarlino S; Brambilla P; Martinelli Boneschi F; Feltri ML; Wrabetz L; Quattrini A; Feinstein E; Huganir RL; Bolino A

2013-09-01

179

Myelination deficit in a phencyclidine-induced neurodevelopmental model of schizophrenia.  

UK PubMed Central (United Kingdom)

Increasing evidence supports an important role of oligodendrocytes and myelination in the pathogenesis of schizophrenia. Oligodendrocytes are the myelin-producing cells in the central nervous system. To test the myelination dysfunction hypothesis of schizophrenia, possible myelination dysfunction was evaluated in a phencyclidine (PCP)-induced neurodevelopmental model of schizophrenia. On postnatal day (PND) 2, rat pups were treated with a total 14 subcutaneous daily injections of PCP (10mg/kg) or saline. PCP-injected rats showed schizophrenia-like behaviors including hyper-locomotor activity on PND 30 and prepulse inhibition deficit on PND 31. Cerebral myelination was measured by the expression of myelin basic protein (MBP), and cerebral mature oligodendrocytes were measured by the expression of glutathione S-transferase (GST)-? in rats. The results indicate that the expressions of MBP on PND 16, 22 and 32 and GST-? on PND 22 decreased in the frontal cortex of PCP-injected rats. Our results suggest that there was myelination impairment in the phencyclidine-induced schizophrenia animal model, and indicate that myelination may play an important role in the pathogenesis of schizophrenia.

Zhang R; He J; Zhu S; Zhang H; Wang H; Adilijiang A; Kong L; Wang J; Kong J; Tan Q; Li XM

2012-08-01

180

DDIT4/REDD1/RTP801 Is a Novel Negative Regulator of Schwann Cell Myelination.  

Science.gov (United States)

Signals that promote myelination must be tightly modulated to adjust myelin thickness to the axonal diameter. In the peripheral nervous system, axonal neuregulin 1 type III promotes myelination by activating erbB2/B3 receptors and the PI3K/AKT/mTOR pathway in Schwann cells. Conversely, PTEN (phosphatase and tensin homolog on chromosome 10) dephosphorylates PtdIns(3,4,5)P3 and negatively regulates the AKT pathway and myelination. Recently, the DLG1/SAP97 scaffolding protein was described to interact with PTEN to enhance PIP3 dephosphorylation. Here we now report that nerves from mice with conditional inactivation of Dlg1 in Schwann cells display only a transient increase in myelin thickness during development, suggesting that DLG1 is a transient negative regulator of myelination. Instead, we identified DDIT4/RTP801/REDD1 as a sustained negative modulator of myelination. We show that DDIT4 is expressed in Schwann cells and its maximum expression level precedes the peak of AKT activation and of DLG1 activity in peripheral nerves. Moreover, loss of DDIT4 expression both in vitro and in vivo in Ddit4-null mice provokes sustained hypermyelination and enhanced mTORC1 activation, thus suggesting that this molecule is a novel negative regulator of PNS myelination. PMID:24048858

Noseda, Roberta; Belin, Sophie; Piguet, Françoise; Vaccari, Ilaria; Scarlino, Stefania; Brambilla, Paola; Martinelli Boneschi, Filippo; Feltri, Maria Laura; Wrabetz, Lawrence; Quattrini, Angelo; Feinstein, Elena; Huganir, Richard L; Bolino, Alessandra

2013-09-18

 
 
 
 
181

Endogenous antibodies promote rapid myelin clearance and effective axon regeneration after nerve injury  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Degenerating myelin inhibits axon regeneration and is rapidly cleared after peripheral (PNS) but not central nervous system (CNS) injury. To better understand mechanisms underlying rapid PNS myelin clearance, we tested the potential role of the humoral immune system. Here, we show that endogenous an...

Vargas, Mauricio E.; Watanabe, Junryo; Singh, Simar J.; Robinson, William H.; Barres, Ben A.

182

BRAIN MYELINATION IN PREVALENT NEUROPSYCHIATRIC DEVELOPMENTAL DISORDERS: PRIMARY AND COMORBID ADDICTION.  

Science.gov (United States)

Current concepts of addiction focus on neuronal neurocircuitry and neurotransmitters and are largely based on animal model data, but the human brain is unique in its high myelin content and extended developmental (myelination) phase that continues until middle age. The biology of our exceptional myelination process and factors that influence it have been synthesized into a recently published myelin model of human brain evolution and normal development that cuts across the current symptom-based classification of neuropsychiatric disorders.The developmental perspective of the model suggests that dysregulations in the myelination process contribute to prevalent early-life neuropsychiatric disorders, as well as to addictions. These disorders share deficits in inhibitory control functions that likely contribute to their high rates of comorbidity with addiction and other impulsive behaviors. The model posits that substances such as alcohol and psychostimulants are toxic to the extremely vulnerable myelination process and contribute to the poor outcomes of primary and comorbid addictive disorders in susceptible individuals.By increasing the scientific focus on myelination, the model provides a rational biological framework for the development of novel, myelin-centered treatments that may have widespread efficacy across multiple disease states and could potentially be used in treating, delaying, or even preventing some of the most prevalent and devastating neuropsychiatric disorders. PMID:18668184

Bartzokis, George

2005-01-01

183

BRAIN MYELINATION IN PREVALENT NEUROPSYCHIATRIC DEVELOPMENTAL DISORDERS: PRIMARY AND COMORBID ADDICTION.  

UK PubMed Central (United Kingdom)

Current concepts of addiction focus on neuronal neurocircuitry and neurotransmitters and are largely based on animal model data, but the human brain is unique in its high myelin content and extended developmental (myelination) phase that continues until middle age. The biology of our exceptional myelination process and factors that influence it have been synthesized into a recently published myelin model of human brain evolution and normal development that cuts across the current symptom-based classification of neuropsychiatric disorders.The developmental perspective of the model suggests that dysregulations in the myelination process contribute to prevalent early-life neuropsychiatric disorders, as well as to addictions. These disorders share deficits in inhibitory control functions that likely contribute to their high rates of comorbidity with addiction and other impulsive behaviors. The model posits that substances such as alcohol and psychostimulants are toxic to the extremely vulnerable myelination process and contribute to the poor outcomes of primary and comorbid addictive disorders in susceptible individuals.By increasing the scientific focus on myelination, the model provides a rational biological framework for the development of novel, myelin-centered treatments that may have widespread efficacy across multiple disease states and could potentially be used in treating, delaying, or even preventing some of the most prevalent and devastating neuropsychiatric disorders.

Bartzokis G

2005-01-01

184

[Number and thickness of myelinic fibres of the phrenic nerve of young and aged rats  

UK PubMed Central (United Kingdom)

The phrenic nerve of albino rats was studied for age changes in number of fibres, myelin sheath thickness and axon calibre. There is no significant morphological differences between nerves from young and aged rats and no difference with age was found in the number of fibres, myelin sheath thickness and axon calibre.

de Souza RR; Watanabe IS; Chadi G; de Araujo MV

1992-02-01

185

Alpha6beta4 integrin and dystroglycan cooperate to stabilize the myelin sheath.  

UK PubMed Central (United Kingdom)

Schwann cells integrate signals deriving from the axon and the basal lamina to myelinate peripheral nerves. Integrin alpha6beta4 is a laminin receptor synthesized by Schwann cells and displayed apposed to the basal lamina. alpha6beta4 integrin expression in Schwann cells is induced by axons at the onset of myelination, and rises in adulthood. The beta4 chain has a uniquely long cytoplasmic domain that interacts with intermediate filaments such as dystonin, important in peripheral myelination. Furthermore, alpha6beta4 integrin binds peripheral myelin protein 22, whose alteration causes the most common demyelinating hereditary neuropathy. All these data suggest a role for alpha6beta4 integrin in peripheral nerve myelination. Here we show that ablating alpha6beta4 integrin specifically in Schwann cells of transgenic mice does not affect peripheral nerve development, myelin formation, maturation, or regeneration. However, consistent with maximal expression in adult nerves, alpha6beta4 integrin-null myelin is more prone to abnormal folding with aging. When the laminin receptor dystroglycan is also ablated, major folding abnormalities occur, associated with acute demyelination in some peripheral nervous system districts. These data indicate that, similar to its role in skin, alpha6beta4 integrin confers stability to myelin in peripheral nerves.

Nodari A; Previtali SC; Dati G; Occhi S; Court FA; Colombelli C; Zambroni D; Dina G; Del Carro U; Campbell KP; Quattrini A; Wrabetz L; Feltri ML

2008-06-01

186

?6?4 integrin and dystroglycan cooperate to stabilize the myelin sheath  

Science.gov (United States)

Schwann cells integrate signals deriving from the axon and the basal lamina to myelinate peripheral nerves. Integrin ?6?4 is a laminin receptor synthesized by Schwann cells and displayed apposed to the basal lamina. ?6?4 integrin expression in Schwann cells is induced by axons at the onset of myelination, and rise in adulthood. The ?4 chain has a uniquely long cytoplasmic domain that interacts with intermediate filaments such as dystonin, important in peripheral myelination. Furthermore, ?6?4 integrin binds peripheral myelin protein 22, whose alteration causes the most common demyelinating hereditary neuropathy. All these data suggest a role for ?6?4 integrin in peripheral nerve myelination. Here we show that ablating ?6?4 integrin specifically in Schwann cells of transgenic mice does not affect peripheral nerve development, myelin formation, maturation or regeneration. However, consistent with maximal expression in adult nerves, ?6?4 integrin-null myelin is more prone to abnormal folding with aging. When the laminin receptor dystroglycan is also ablated, major folding abnormalities occur, associated with acute demyelination in some peripheral nervous system districts. These data indicate that, similar to its role in skin, ?6?4 integrin confers stability to myelin in peripheral nerves.

Nodari, A.; Previtali, S.C.; Dati, G.; Occhi, S.; Court, FA.; Colombelli, C.; Zambroni, D.; Dina, G.; Del Carro, U.; Campbell, K. P.; Quattrini, A.; Wrabetz, L.; Feltri, ML.

2008-01-01

187

Alpha6beta4 integrin and dystroglycan cooperate to stabilize the myelin sheath.  

Science.gov (United States)

Schwann cells integrate signals deriving from the axon and the basal lamina to myelinate peripheral nerves. Integrin alpha6beta4 is a laminin receptor synthesized by Schwann cells and displayed apposed to the basal lamina. alpha6beta4 integrin expression in Schwann cells is induced by axons at the onset of myelination, and rises in adulthood. The beta4 chain has a uniquely long cytoplasmic domain that interacts with intermediate filaments such as dystonin, important in peripheral myelination. Furthermore, alpha6beta4 integrin binds peripheral myelin protein 22, whose alteration causes the most common demyelinating hereditary neuropathy. All these data suggest a role for alpha6beta4 integrin in peripheral nerve myelination. Here we show that ablating alpha6beta4 integrin specifically in Schwann cells of transgenic mice does not affect peripheral nerve development, myelin formation, maturation, or regeneration. However, consistent with maximal expression in adult nerves, alpha6beta4 integrin-null myelin is more prone to abnormal folding with aging. When the laminin receptor dystroglycan is also ablated, major folding abnormalities occur, associated with acute demyelination in some peripheral nervous system districts. These data indicate that, similar to its role in skin, alpha6beta4 integrin confers stability to myelin in peripheral nerves. PMID:18579745

Nodari, Alessandro; Previtali, Stefano C; Dati, Gabriele; Occhi, Simona; Court, Felipe A; Colombelli, Cristina; Zambroni, Desirée; Dina, Giorgia; Del Carro, Ubaldo; Campbell, Kevin P; Quattrini, Angelo; Wrabetz, Lawrence; Feltri, M Laura

2008-06-25

188

The central role of Fyn kinase in axon-glial signalling and translation of myelin proteins  

Digital Repository Infrastructure Vision for European Research (DRIVER)

During central nervous system myelination, oligodendrocytes extend membrane processes towards an axonal contact site which is followed by ensheathment resulting in a compacted multilamellar myelin sheath. The formation of this axon-glial unit facilitates rapid saltatory propagation of action potenti...

White, Robin

189

[Synapses with myelinated and unmyelinated preterminal portions of axons in cat cerebral cortex  

UK PubMed Central (United Kingdom)

The electron microscopic study of the cat cerebral cortex revealed two kinds of preterminal axonal regions with synaptic boutons at the end: nonmyelinated and myelinated. In the first case their diameter was about 90 nm; in the second case it was considerably greater; the myelin could reach the bouton. The possible physiological meaning of these structural features is discussed.

Mikeladze AL; Ro?tbak AI; Lazriev IL

1979-01-01

190

Myelination in coculture of established neuronal and Schwann cell lines.  

UK PubMed Central (United Kingdom)

Establishing stable coculture systems with neuronal and Schwann cell lines has been considered difficult, presumably because of their high proliferative activity and phenotypic differences from primary cultured cells. The present study is aimed at developing methods for myelin formation under coculture of the neural crest-derived pheochromocytoma cell line PC12 and the immortalized adult rat Schwann cell line IFRS1. Prior to coculture, PC12 cells were seeded at low density (3 × 10(2)/cm(2)) and maintained in serum-free medium with N2 supplement, ascorbic acid (50 ?g/ml), and nerve growth factor (NGF) (50 ng/ml) for a week. Exposure to such a NGF-rich environment with minimum nutrients accelerated differentiation and neurite extension, but not proliferation, of PC12 cells. When IFRS1 cells were added to NGF-primed PC12 cells, the cell density ratio of PC12 cells to IFRS1 cells was adjusted from 1:50 to 1:100. The cocultured cells were then maintained in serum-free medium with B27 supplement, ascorbic acid (50 ?g/ml), NGF (10 ng/ml), and recombinant soluble neuregulin-1 type III (25 ng/ml). Myelin formation was illustrated by light and electron microscopy performed at day 28 of coculture. The stable PC12-IFRS1 coculture system is free of technical and ethical problems arising from the primary culture and can be a valuable tool to study peripheral nerve degeneration and regeneration.

Sango K; Kawakami E; Yanagisawa H; Takaku S; Tsukamoto M; Utsunomiya K; Watabe K

2012-06-01

191

Myelin glycosphingolipid immunoreactivity and CSF levels in multiple sclerosis.  

UK PubMed Central (United Kingdom)

OBJECTIVES: Patients with multiple sclerosis were reported to harbour antibodies not only against proteins and glycoproteins but also against glycolipids, including sulfatide and galactosylceramide (GalCer), the two major glycosphingolipids of myelin. However, previous results were inconsistent concerning glycosphingolipid levels, antibody type, dominance of serum or Cerebrospinal fluid compartments and relationship to the multiple sclerosis (MS) course. RESULTS: We hereby report that the cerebrospinal fluid levels of sulfatide were increased in patients with MS (n = 46) compared with controls (n = 50, P < 0.001). In addition, patients had higher serum IgM anti-glycosphingolipid titres than controls (P = 0.03 for sulfatide, <0.001 for GalCer), while the anti-glycosphingolipid IgM antibodies in the cerebrospinal fluid were essentially normal. However, in seven of 46 patients cerebrospinal fluid IgG antibodies against GalCer (P = 0.004) could be detected, which was not found in any of the control individuals, and this finding might mirror the occurrence of more specific B-cell clones behind the blood-brain barrier. CONCLUSIONS: The IgM immunoreactivity in serum did not show any relationship to the type of course or severity of MS, arguing against a phenomenon secondary to myelin damage. Thus, the IgM antibody findings are compatible with an early antigen challenge or autoimmunity associated with natural antibodies.

Haghighi S; Lekman A; Nilsson S; Blomqvist M; Andersen O

2012-01-01

192

Entrapment in anti myelin-associated glycoprotein neuropathy.  

UK PubMed Central (United Kingdom)

Anti-myelin associated glycoprotein (MAG) neuropathy is a chronic disorder in which IgM antibodies react with Schwann cell glycoproteins, including MAG and peripheral myelin protein 22 (PMP22). Nerve conduction studies show features of axon loss and predominantly distal slowing consistent with demyelination. Because a genetic loss of PMP22 function yields hereditary neuropathy with liability to pressure palsies (HNPP), loss of PMP22 function due to anti- MAG antibodies may result in increased sensitivity to entrapment. We investigated this by performing standardized electrophysiological studies in 16 patients with anti-MAG neuropathy and 16 disease controls with genetically confirmed HNPP. Disproportionate slowing relative to adjacent segments occurred in similar proportions of patients with anti-MAG neuropathy and HNPP, and was of the same magnitude in each group. Affected were the elbow, carpal tunnel and the wrist-hand segments of the median and ulnar nerves. However, in anti-MAG neuropathy as compared to HNPP, absolute values of distal motor latencies and conduction velocities outside entrapment sites were slower and amplitudes were lower. In conclusion, increased sensitivity for entrapment may occur in anti-MAG neuropathy and contribute to part of the nerve damage.

Faber CG; Notermans NC; Wokke JH; Franssen H

2009-04-01

193

[The myelin mutant taiep as a model for abscence crisis].  

UK PubMed Central (United Kingdom)

BACKGROUND: Taiep rat is a myelin mutant rat with hypomyelination followed by progressive demyelination. This mutant presents cortical discharges with a spindle form, with an ascending and descending phases similar to absence epilepsy. METHODS: Taiep rats were maintained under standard animal room conditions with free access to balanced rodent pellets and tap water. Rats were anesthetized with chloral hydrate under aseptic conditions; three stainless steel screws and a bipolar electrode were implanted in the hippocampus. The signals were amplified, filtered and recorded using a video-EEG Harmonie system (Canada). All data were analyzed using Sensa and Luna modules. RESULTS: Our results showed that taiep rats have spike-wave discharges (SWD) during wake, slow wake sleep (SWS) and rapid eye movement (REM), being statistically higher and longer during awake period than SWS or REM sleep. The systemic administration of pilocarpine, a cholinergic agonist, increased dramatically the cortical discharges with five characteristic seizures patterns and concomitantly decreased the frequency and duration of absence crisis. However, only 80% of the taiep rats tested showed this paroxysm. On the other hand, 100% of control Sprague-Dawley rats showed tonic clonic seizures, indicating some type of resistance to this muscarinic cholinergic drug in taiep rats. CONCLUSIONS: These results showed that the taiep rat, a myelin mutant, is a good model for the electrophysiological and pharmacological study of absence epilepsy, particularly considering its resistance to pilocarpine-induced seizures.

Eguibar JR; Cortés Mdel C

2010-01-01

194

[Neurophysiological study of thin myelinated and unmyelinated fibers  

UK PubMed Central (United Kingdom)

INTRODUCTION: Standard neurophysiological techniques evaluate thick myelinated fibers. Yet, peripheral nerves are equally composed of thin myelinated and unmyelinated fibers. The latter are responsible for autonomic function as well as temperature and pain perception. DEVELOPMENT: Microneurographic studies are restricted to investigation laboratories. Since the techniques are complex and invasive, their performance is still poor for clinical purposes and some of the components to be analyzed, such as cardiovagal, cannot be directly recorded. The clinical need to evaluate the functions regulated by the autonomic nervous system (ANS) had led to devising a series of tests which, in most cases, rely on reflex responses evoked by already known standardize stimuli. The battery chosen has to be non invasive, reproducible, specific, providing relevant data to the investigated function, with a readily available technology, which has to be managed being aware of the physiological and pathological factors that might bear an influence on the results. The recent development of heart rate and blood pressure power spectral analysis, provides a new interesting insight for quantification of ANS abnormalities. The study of thermography and thermometry of body surface brings forward evidence on the activity of other thin and unmyelinated fibers components of the peripheral nerve spectrum. CONCLUSION: The adequate management of the above mentioned tests gives rise to a more extensive and appropriate knowledge of the whole peripheral nerve fiber spectrum.

Espinosa ML; Santiago S; Guzmán JJ; Prieto J; Ferrer T

1999-03-01

195

Myelination process in the rat sciatic nerve during regeneration and development: molecular species composition and acyl group biosynthesis of choline-, ethanolamine-, and serine-glycerophospholipids of myelin fractions.  

UK PubMed Central (United Kingdom)

The content of alkenyl-acyl, alkyl-acyl and diacyl types of the three major myelin glycerophospholipids such as PtdCho, PtdEtn and PtdSer was determined in myelin fractions prepared from sciatic nerve segments of rats at 12, 25 and 45 days after birth, and of adult rats (6-month-old) 90 days after crush injury. The biosynthesis and metabolic heterogeneity of lipid classes and types were also studied by incubation with [1-14C] acetate of nerve segments of young rats at different ages as well as crushed and sham-operated control nerve segments of adult rats. The analysis of composition and positional distribution in major individual molecular species extracted from light myelin and myelin-related fraction suggest that the metabolism of alkenyl-acyl-glycerophosphorylethanolamines and unsaturated species of PtdCho and PtdSer may not be regulated in the same manner during peripheral nerve myelination of developing rat and remyelination of regenerating nerve in the adult animal. The 14C-radioactivity incorporation into lipid classes and alkyl and acyl moieties of the three major phospholipids of sciatic nerve segments during the developmental period investigated revealed that Schwann cells were capable of synthesizing acyl-linked fatty acids in both myelin fractions at a decreasing rate and with different patterns during development. In regenerating sciatic nerve of adult animals the labeling of myelin lipid classes and types of remyelinating nerve segment distal to the crush site was markedly higher than that of sham-operated normal one; however, the magnitude and the pattern of the specific radioactivity never approached those observed during active myelination of the nerve in young animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Alberghina M; Viola M; Giuffrida AM

1984-07-01

196

Knockdown of Dock7 in vivo specifically affects myelination by Schwann cells and increases myelin thickness in sciatic nerves without affecting axon thickness  

Directory of Open Access Journals (Sweden)

Full Text Available During development of the peripheral nervous system (PNS), Schwann cells (SCs) wrap individual axons to form myelin sheaths, which act as surrounding insulators and markedly enhance the propagation of the action potential. In peripheral neuropathies such as Guillain-Barré syndrome (GBS) and inherited demyelinating Charcot-Marie-Tooth (CMT) disease and diabetic neuropathies, chronic demyelination and defective remyelination are repeated, causing more severe neuropathies. It is thus thought that development of a drug that promotes proper myelination with minimal side effects could provide an effective therapy for these diseases. As yet, however, little is known about therapeutic target molecules and genetically-modified mice for testing such approaches. We previously cloned the dock7 gene and characterized Dock7 as the regulator controlling SC myelination; however, an important issue, whether knockdown of Dock7 specifically affects myelination by SCs but not leaves neurons unaffected, has remained unclear. Here, we generate newly-produced transgenic mice harboring short-hairpin RNA (shRNA) targeting Dock7. We also describe that Dock7 shRNA transgenic mice exhibit enhanced myelin thickness without affecting axon thickness in sciatic nerves of the PNS, as reduced thickness of the axon diameter is the primary indicator of denatured neurons. Similarly, purified in vitro SC-neuronal cocultures established from transgenic mice exhibit enhanced formation of myelin segments, suggesting that knockdown of Dock7 promotes myelination by SCs. Collectively, Dock7 knockdown specifically affects SC myelination in sciatic nerves, providing evidence that Dock7 may be a promising drug-target-specific molecules for developing a therapy for peripheral neuropathies that aims to enhance myeliantion.

Tomohiro Torii; Yuki Miyamoto; Motoshi Nagao; Naoko Onami; Hideki Tsumura; Masahiro Maeda; Kazuaki Nakamura; Akito Tanoue; Junji Yamauchi

2012-01-01

197

Subclinical CNS inflammation as response to a myelin antigen in humanized mice.  

Science.gov (United States)

Multiple sclerosis is a demyelinating autoimmune disease of the CNS. Its animal model experimental autoimmune encephalomyelitis is commonly induced by active immunization with myelin antigens. To investigate human immune responses against myelin antigens in vivo we established a new subclinical experimental autoimmune encephalomyelitis model in humanized mice. NOD/Scid?c(-/-) animals were transferred with peripheral blood mononuclear cells from healthy human donors and immunized with myelin antigens in complete Freund's adjuvant and antigen-pulsed autologous dendritic cells. Human T cells recovered from these animals reacted specifically to the soluble domain of myelin oligodendrocyte glycoprotein and secreted proinflammatory cytokines. Furthermore, immunized animals developed subclinical CNS inflammation with infiltrating CD4(+) and CD8(+) T cells and production of encephalitogenic cytokines. Thus, this model of myelin-induced CNS inflammation by human T cells may allow testing of new human-specific therapeuticals for multiple sclerosis. PMID:23640521

Zayoud, Morad; El Malki, Khalifa; Frauenknecht, Katrin; Trinschek, Bettina; Kloos, Luise; Karram, Khalad; Wanke, Florian; Georgescu, Julia; Hartwig, Udo F; Sommer, Clemens; Jonuleit, Helmut; Waisman, Ari; Kurschus, Florian C

2013-05-03

198

A quantitative measure of myelination development in infants, using MR images  

International Nuclear Information System (INIS)

The objective of this study was to measure myelination of frontal lobe changes in infants and young children. Twenty-four cases of infants and children (age range 12-121 months) were evaluated by a quantitative assessment of T2-weighted MR image features. Reliable quantitative changes between white and gray matter correlated with developmental age in a group of children with no neurological findings. Myelination appears to be an increasing exponential function with the greatest rate of change occurring over the first 3 years of life. The quantitative changes observed were in accordance with previous qualitative judgments of myelination development. Children with periventricular leukomalacia (PVL) showed delays in achieving levels of myelination when compared to normal children and adjusted for chronological age. The quantitative measure of myelination development may prove to be useful in assessing the stages of development and helpful in the quantitative descriptions of white matter disorders such as PVL. (orig.)

2004-01-01

199

A quantitative measure of myelination development in infants, using MR images  

Energy Technology Data Exchange (ETDEWEB)

The objective of this study was to measure myelination of frontal lobe changes in infants and young children. Twenty-four cases of infants and children (age range 12-121 months) were evaluated by a quantitative assessment of T2-weighted MR image features. Reliable quantitative changes between white and gray matter correlated with developmental age in a group of children with no neurological findings. Myelination appears to be an increasing exponential function with the greatest rate of change occurring over the first 3 years of life. The quantitative changes observed were in accordance with previous qualitative judgments of myelination development. Children with periventricular leukomalacia (PVL) showed delays in achieving levels of myelination when compared to normal children and adjusted for chronological age. The quantitative measure of myelination development may prove to be useful in assessing the stages of development and helpful in the quantitative descriptions of white matter disorders such as PVL. (orig.)

Carmody, Dennis P. [Robert Wood Johnson Medical School, New Brunswick, NJ (United States); Dunn, Stanley M.; Boddie-Willis, Akiza S. [The State University of New Jersey, Rutgers, New Brunswick, NJ (United States); DeMarco, J. Kevin [Laurie Imaging Center, New Brunswick, NJ (United States); Lewis, Michael [Robert Wood Johnson Medical School, New Brunswick, NJ (United States); Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Institute for the Study of Child Development, New Brunswick (United States)

2004-09-01

200

Rnh1 promotes differentiation and myelination via RhoA in oligodendrocytes.  

UK PubMed Central (United Kingdom)

Increases in Rattus norvegicus ribonuclease/angiogenin inhibitor 1 (Rnh1) are observed in rat primary neuron injury and/or the regeneration process and in differentiated oligodendrocytes. However, the roles of Rnh1 in the central nervous system are still largely unexplored. RhoA is an important signaling protein that has been implicated in oligodendrocyte differentiation and myelination. We demonstrate enhanced differentiation and myelination of oligodendrocytes mediated by Rnh1 in vitro. We further show that Rnh1 is expressed in oligodendrocyte precursors and oligodendrocytes. Importantly, Rnh1 strongly affects oligodendrocyte differentiation through RhoA-ROCK signaling. Moreover, changes in Rnh1 expression in oligodendrocytes regulates the expression and phosphorylation of Fyn, a regulator of RhoA activity. Finally, Rnh1 promotes myelination in vitro. These results show that Rnh1-mediated RhoA inactivation enhances the differentiation and myelination in oligodendrocytes. Overall, Rnh1 might contribute to oligodendrocyte differentiation and myelination processes in vitro.

Zhao CF; Liu Y; Que HP; Yang SG; Liu T; Liu ZQ; Hui HD; Liu S

2013-09-01

 
 
 
 
201

Contribution of axonal transport to the renewal of myelin phospholipids in peripheral nerves. I  

International Nuclear Information System (INIS)

Kinetics of phospholipid constituents transferred from the axon to the myelin sheath were studied in the oculomotor nerve (OMN) and the ciliary ganglion (CG) of chicken. Axons of the OMN were loaded with transported phospholipids after an intracerebral injection of [2-3H]glycerol or [3H]labeled choline. Quantitative electron microscope radioautography revealed that labeled lipids were transported in the axons mainly associated with the smooth endoplasmic reticulum. Simultaneously, the labeling of the myelin sheath was found in the Schmidt-Lanterman clefts and the inner myelin layers. The outer Schwann cell cytoplasm and the outer myelin layers contained some label with [methyl-3H]choline, but virtually none with [2-3H]glycerol. With time the radioactive lipids were redistributed throughout and along the whole myelin sheath. (Auth.).

1981-01-01

202

Splitting criterion for reflexive sheaves  

CERN Document Server

The purpose of this paper is to study the structure of reflexive sheaves over projective spaces through hyperplane sections. We give a criterion for a reflexive sheaf to split into a direct sum of line bundles. An application to the theory of free hyperplane arrangements is also given.

Abe, T; Abe, Takuro; Yoshinaga, Masahiko

2005-01-01

203

Resurgent functions and splitting problems  

CERN Multimedia

The present text is an introduction to \\'Ecalle's theory of resurgent functions and alien calculus, in connection with problems of exponentially small separatrix splitting. An outline of the resurgent treatment of Abel's equation for resonant dynamics in one complex variable is included. The emphasis is on examples of nonlinear difference equations, as a simple and natural way of introducing the concepts.

Sauzin, David

2006-01-01

204

A mathematical based calculation of a myelinated segment in axons.  

UK PubMed Central (United Kingdom)

The brain is a complicated system that controls all of the body's actions and reactions by receiving and processing different stimuli and producing the proper responses. The brain accomplishes this task using various sensory elements such as neurons. The axon is the most important element of the neuron in terms of signal generation and propagation. Although much effort has been made studying the characteristics of the axon, there is no research that focuses on measuring the length of this element from a mathematical point of view. In this paper, we propose for the first time a new mathematical model of the generation of action potentials in the axon. Using this model and the diffusion phenomenon in axons, we propose a characteristic length for the myelinated segments in axons. This mathematically calculated value is corroborated by comparison with values measured by biologists.

Namazi H; Kulish VV

2013-07-01

205

Microresonators: Particle sizing by mode splitting  

Science.gov (United States)

It has long been known that the optical resonances of ultrahigh-Q whispering gallery mode resonators can split under the influence of particle scattering. Now scientists have exploited this splitting to accurately determine particle sizes.

Kippenberg, Tobias J.

2010-01-01

206

Myelin-associated glycoprotein-related neuropathy associated with psoriasis: a case report  

Science.gov (United States)

Introduction Psoriasis vulgaris is a common inflammatory disease of the skin, and myelin-associated glycoprotein-related neuropathy is a chronic sensory-predominant polyneuropathy. Although both of these diseases are considered autoimmune diseases, psoriasis with concomitant myelin-associated glycoprotein-related neuropathy is very rare. Here, we report a case of myelin-associated glycoprotein-related neuropathy associated with psoriasis. Case presentation A 66-year-old Japanese man, having experienced sternocostoclavicular pain for ten years, was admitted to our hospital because of gait disturbance and numbness of the limbs. Our patient had normal cranial nerve function and normal limb muscle strength. His vibratory and position sense was severely impaired and his touch, temperature and pinprick sensations were mildly disturbed in a glove and stocking distribution. A myelin-associated glycoprotein western blot analysis showed the presence of a 91 to 94kDa band using purified human myelin-associated glycoprotein antigen. His skin lesions were moderately pruritic and Auspitz’s sign was positive. Our patient also showed osteitis of his clavicle and manubrium. We diagnosed our patient with myelin-associated glycoprotein-related neuropathy associated with psoriatic arthritis. Five days after intravenous immunoglobulin therapy, his deep sensory impairment began to improve and his sternocostoclavicular pain diminished dramatically. Conclusions Because myelin-associated glycoprotein-related neuropathy and psoriatic arthritis are both considered autoimmune diseases, we conclude that intravenous immunoglobulin therapy is very effective for patients with an association of these diseases.

2013-01-01

207

Gangliosides of human, cat, and rabbit spinal cords and cord myelin.  

UK PubMed Central (United Kingdom)

Gangliosides were isolated from whole spinal cords and cord myelin of human, cat, and rabbit by a revised methodology. The method included the sequential application of DEAE-Sephadex column chromatography, base treatment, Sephadex G-50 column chromatography, and finally Iatrobeads column chromatography. The human whole spinal cord was found to contain about one-tenth of the ganglioside concentration as in cerebral gray matter and about one-third of that in cerebral white matter. Low levels of gangliosides were also found in cat and rabbit whole cords. Only N-acetyl neuraminic acid could be detected in the ganglioside fractions of all three species. The whole cords also possessed unique ganglioside patterns when compared with the patterns of cerebral tissues. The most prominent and consistent features were the reduced concentration of Gd1a and increased amounts of Gm3 and Gd3. Human, but not cat and rabbit, spinal cord also contained Gm4 as one of the major gangliosides. Myelin prepared from the spinal cords of all three species also contained gangliosides. The amounts were only about half of those in the respective cerebral white matter myelin. The cord myelin ganglioside pattern was generally similar to the cerebral white matter myelin within the same species. Gm1 was the most abundant ganglioside in the cord myelin. Gm4 was found to be highly enriched only in myelin prepared from human sources.

Ueno K; Ando S; Yu RK

1978-09-01

208

Myelin-associated glycoprotein-related neuropathy associated with psoriasis: a case report.  

UK PubMed Central (United Kingdom)

UNLABELLED: INTRODUCTION: Psoriasis vulgaris is a common inflammatory disease of the skin, and myelin-associated glycoprotein-related neuropathy is a chronic sensory-predominant polyneuropathy. Although both of these diseases are considered autoimmune diseases, psoriasis with concomitant myelin-associated glycoprotein-related neuropathy is very rare. Here, we report a case of myelin-associated glycoprotein-related neuropathy associated with psoriasis. CASE PRESENTATION: A 66-year-old Japanese man, having experienced sternocostoclavicular pain for ten years, was admitted to our hospital because of gait disturbance and numbness of the limbs. Our patient had normal cranial nerve function and normal limb muscle strength. His vibratory and position sense was severely impaired and his touch, temperature and pinprick sensations were mildly disturbed in a glove and stocking distribution. A myelin-associated glycoprotein western blot analysis showed the presence of a 91 to 94kDa band using purified human myelin-associated glycoprotein antigen. His skin lesions were moderately pruritic and Auspitz's sign was positive. Our patient also showed osteitis of his clavicle and manubrium. We diagnosed our patient with myelin-associated glycoprotein-related neuropathy associated with psoriatic arthritis. Five days after intravenous immunoglobulin therapy, his deep sensory impairment began to improve and his sternocostoclavicular pain diminished dramatically. CONCLUSIONS: Because myelin-associated glycoprotein-related neuropathy and psoriatic arthritis are both considered autoimmune diseases, we conclude that intravenous immunoglobulin therapy is very effective for patients with an association of these diseases.

Murata KY; Miwa H; Kondo T

2013-01-01

209

Single myelin fiber imaging in living rodents without labeling by deep optical coherence microscopy  

Science.gov (United States)

Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool. However, in vivo imaging has been limited to either low-resolution techniques unable to resolve individual fibers or to low-penetration imaging of single fibers, which cannot provide quantitative information about large volumes of tissue, as required for diagnostic purposes. Here, we perform myelin imaging without labeling and at micron-scale resolution with >300-?m penetration depth on living rodents. This was achieved with a prototype [termed deep optical coherence microscopy (deep-OCM)] of a high-numerical aperture infrared full-field optical coherence microscope, which includes aberration correction for the compensation of refractive index mismatch and high-frame-rate interferometric measurements. We were able to measure the density of individual myelinated fibers in the rat cortex over a large volume of gray matter. In the peripheral nervous system, deep-OCM allows, after minor surgery, in situ imaging of single myelinated fibers over a large fraction of the sciatic nerve. This allows quantitative comparison of normal and Krox20 mutant mice, in which myelination in the peripheral nervous system is impaired. This opens promising perspectives for myelin chronic imaging in demyelinating diseases and for minimally invasive medical diagnosis.

Ben Arous, Juliette; Binding, Jonas; Léger, Jean-François; Casado, Mariano; Topilko, Piotr; Gigan, Sylvain; Claude Boccara, A.; Bourdieu, Laurent

2011-11-01

210

Uncoupling of neuroinflammation from axonal degeneration in mice lacking the myelin protein tetraspanin-2.  

Science.gov (United States)

Deficiency of the major constituent of central nervous system (CNS) myelin, proteolipid protein (PLP), causes axonal pathology in spastic paraplegia type-2 patients and in Plp1(null) -mice but is compatible with almost normal myelination. These observations led us to speculate that PLP's role in myelination may be partly compensated for by other tetraspan proteins. Here, we demonstrate that the abundance of the structurally related tetraspanin-2 (TSPAN2) is highly increased in CNS myelin of Plp1(null) -mice. Unexpectedly, Tspan2(null) -mutant mice generated by homologous recombination in embryonic stem cells displayed low-grade activation of astrocytes and microglia in white matter tracts while they were fully myelinated and showed no signs of axonal degeneration. To determine overlapping functions of TSPAN2 and PLP, Tspan2(null) *Plp1(null) double-mutant mice were generated. Strikingly, the activation of astrocytes and microglia was strongly enhanced in Tspan2(null) *Plp1(null) double-mutants compared with either single-mutant, but the levels of dysmyelination and axonal degeneration were not increased. In this model, glial activation is thus unlikely to be caused by axonal pathology, and vice versa does not potentiate axonal degeneration. Our results support the concept that multiple myelin proteins have distinct roles in the long-term preservation of a healthy CNS, rather than in myelination per se. GLIA 2013;61:1832-1847. PMID:24038504

de Monasterio-Schrader, Patricia; Patzig, Julia; Möbius, Wiebke; Barrette, Benoit; Wagner, Tadzio L; Kusch, Kathrin; Edgar, Julia M; Brophy, Peter J; Werner, Hauke B

2013-08-30

211

Oxydative phosphorylation in sciatic nerve myelin and its impairment in a model of dysmyelinating peripheral neuropathy.  

Science.gov (United States)

Myelin sheath is the proteolipid membrane wrapping the axons of CNS and PNS. We have shown data suggesting that CNS myelin conducts oxidative phosphorylation (OXPHOS), challenging its role in limiting the axonal energy expenditure. Here, we focused on PNS myelin. Samples were: (i) isolated myelin vesicles (IMV) from sciatic nerves, (ii) mitochondria from primary Schwann cell cultures, and (iii) sciatic nerve sections, from wild type or Charcot-Marie-Tooth type 1A (CMT1A) rats. The latter used as a model of dys-demyelination. O? consumption and activity of OXPHOS proteins from wild type (Wt) or CMT1A sciatic nerves showed some differences. In particular, O? consumption by IMV from Wt and CMT1A 1-month-old rats was comparable, while it was severely impaired in IMV from adult affected animals. Mitochondria extracted from CMT1A Schwann cell did not show any dysfunction. Transmission electron microscopy studies demonstrated an increased mitochondrial density in dys-demyelinated axons, as to compensate for the loss of respiration by myelin. Confocal immunohistochemistry showed the expression of OXPHOS proteins in the myelin sheath, both in Wt and dys-demyelinated nerves. These revealed an abnormal morphology. Taken together these results support the idea that also PNS myelin conducts OXPHOS to sustain axonal function. PMID:23578247

Ravera, Silvia; Nobbio, Lucilla; Visigalli, Davide; Bartolucci, Martina; Calzia, Daniela; Fiorese, Fulvia; Mancardi, Gianluigi; Schenone, Angelo; Morelli, Alessandro; Panfoli, Isabella

2013-04-30

212

Developmental changes in myelin-induced proliferation of cultured Schwann cells  

Energy Technology Data Exchange (ETDEWEB)

Schwann cell proliferation induced by a myelin-enriched fraction was examined in vitro. Although nearly all the Schwann cells contained material that was recognized by antisera to myelin basic protein after 24 h, only 1% of the cells were synthesizing DNA. 72 h after the addition of the mitogen a maximum of 10% of the cells incorporated (/sup 3/H)thymidine. If the cultures were treated with the myelin-enriched fraction for 24 h and then washed, the number of proliferating Schwann cells decreased by 75% when compared with those cells that were incubated with the mitogen continuously. When Schwann cells were labeled with (/sup 14/C)thymidine followed by a pulse of (/sup 3/H)thymidine 24 h later, every Schwann cell labeled with (/sup 3/H)thymidine was also labeled with (/sup 14/C)thymidine. Although almost every Schwann cell can metabolize the myelin membranes within 24 h of exposure, a small population of cell initially utilizes the myelin as a mitogen, and this population continues to divide only if myelin is present in the extracellular media. The percentage of the Schwann cells that initially recognize the myelin-enriched fraction as a mitogen is dependent upon the age of the animal from which the cells were prepared.

Yoshino, J.E.; Mason, P.W.; DeVries, G.H.

1987-03-01

213

Oxydative phosphorylation in sciatic nerve myelin and its impairment in a model of dysmyelinating peripheral neuropathy.  

UK PubMed Central (United Kingdom)

Myelin sheath is the proteolipid membrane wrapping the axons of CNS and PNS. We have shown data suggesting that CNS myelin conducts oxidative phosphorylation (OXPHOS), challenging its role in limiting the axonal energy expenditure. Here, we focused on PNS myelin. Samples were: (i) isolated myelin vesicles (IMV) from sciatic nerves, (ii) mitochondria from primary Schwann cell cultures, and (iii) sciatic nerve sections, from wild type or Charcot-Marie-Tooth type 1A (CMT1A) rats. The latter used as a model of dys-demyelination. O? consumption and activity of OXPHOS proteins from wild type (Wt) or CMT1A sciatic nerves showed some differences. In particular, O? consumption by IMV from Wt and CMT1A 1-month-old rats was comparable, while it was severely impaired in IMV from adult affected animals. Mitochondria extracted from CMT1A Schwann cell did not show any dysfunction. Transmission electron microscopy studies demonstrated an increased mitochondrial density in dys-demyelinated axons, as to compensate for the loss of respiration by myelin. Confocal immunohistochemistry showed the expression of OXPHOS proteins in the myelin sheath, both in Wt and dys-demyelinated nerves. These revealed an abnormal morphology. Taken together these results support the idea that also PNS myelin conducts OXPHOS to sustain axonal function.

Ravera S; Nobbio L; Visigalli D; Bartolucci M; Calzia D; Fiorese F; Mancardi G; Schenone A; Morelli A; Panfoli I

2013-07-01

214

Soluble Neuregulin and Schwann Cell Myelination: a Therapeutic Potential for Improving Remyelination of Adult Axons  

Directory of Open Access Journals (Sweden)

Full Text Available Myelination in the peripheral nervous system (PNS) is induced by close contact signaling between axons and Schwann cells. Previous studies have identified membrane-bound neuregulin-1 (Nrg1) type III, expressed on the axons, as the key instructive signal that regulates Schwann cell myelination. In our recent study, we show that recombinant soluble Nrg1 elicits a similar pro-myelinating effect on Schwann cells, albeit in a dosage-dependent manner: Nrg1 promotes myelination at low concentrations but inhibits it at high concentrations. The inhibitory effect of Nrg1 is mediated through its activation of the Ras/Raf/Erk pathway in Schwann cells, and inhibition of the pathway using a pharmacologic inhibitor restores myelination. We also show that soluble Nrg1 enhances myelination on axons that do not express sufficient amount of Nrg1 type III needed for robust myelination. These findings are significant as they suggest that combined therapies aimed at enhancing Nrg1 signaling and blocking the Ras/Raf/Erk activation may be an effective strategy for improving remyelination on adult axons, which, as shown in our recent data, express low levels of Nrg1 type III. In this report we provide an overview of our recent findings and discuss the therapeutic potential of soluble Nrg1.

Neeraja Syed; Haesun A. Kim

2010-01-01

215

Developmental changes in myelin-induced proliferation of cultured Schwann cells  

International Nuclear Information System (INIS)

Schwann cell proliferation induced by a myelin-enriched fraction was examined in vitro. Although nearly all the Schwann cells contained material that was recognized by antisera to myelin basic protein after 24 h, only 1% of the cells were synthesizing DNA. 72 h after the addition of the mitogen a maximum of 10% of the cells incorporated [3H]thymidine. If the cultures were treated with the myelin-enriched fraction for 24 h and then washed, the number of proliferating Schwann cells decreased by 75% when compared with those cells that were incubated with the mitogen continuously. When Schwann cells were labeled with [14C]thymidine followed by a pulse of [3H]thymidine 24 h later, every Schwann cell labeled with [3H]thymidine was also labeled with [14C]thymidine. Although almost every Schwann cell can metabolize the myelin membranes within 24 h of exposure, a small population of cell initially utilizes the myelin as a mitogen, and this population continues to divide only if myelin is present in the extracellular media. The percentage of the Schwann cells that initially recognize the myelin-enriched fraction as a mitogen is dependent upon the age of the animal from which the cells were prepared.

1987-01-01

216

Uncoupling of neuroinflammation from axonal degeneration in mice lacking the myelin protein tetraspanin-2.  

UK PubMed Central (United Kingdom)

Deficiency of the major constituent of central nervous system (CNS) myelin, proteolipid protein (PLP), causes axonal pathology in spastic paraplegia type-2 patients and in Plp1(null) -mice but is compatible with almost normal myelination. These observations led us to speculate that PLP's role in myelination may be partly compensated for by other tetraspan proteins. Here, we demonstrate that the abundance of the structurally related tetraspanin-2 (TSPAN2) is highly increased in CNS myelin of Plp1(null) -mice. Unexpectedly, Tspan2(null) -mutant mice generated by homologous recombination in embryonic stem cells displayed low-grade activation of astrocytes and microglia in white matter tracts while they were fully myelinated and showed no signs of axonal degeneration. To determine overlapping functions of TSPAN2 and PLP, Tspan2(null) *Plp1(null) double-mutant mice were generated. Strikingly, the activation of astrocytes and microglia was strongly enhanced in Tspan2(null) *Plp1(null) double-mutants compared with either single-mutant, but the levels of dysmyelination and axonal degeneration were not increased. In this model, glial activation is thus unlikely to be caused by axonal pathology, and vice versa does not potentiate axonal degeneration. Our results support the concept that multiple myelin proteins have distinct roles in the long-term preservation of a healthy CNS, rather than in myelination per se. GLIA 2013.

de Monasterio-Schrader P; Patzig J; Möbius W; Barrette B; Wagner TL; Kusch K; Edgar JM; Brophy PJ; Werner HB

2013-08-01

217

Salt splitting using ceramic membranes  

Energy Technology Data Exchange (ETDEWEB)

Inorganic ceramic membranes for salt splitting of radioactively contaminated sodium salt solutions are being developed for treating US Department of Energy tank wastes. The process consists of electrochemical separation of sodium ions from the salt solution using sodium (Na) Super Ion Conductors (NaSICON) membranes. In contrast to conventional organic-based bipolar or ion exchange membranes used in salt splitting, NaSICON membranes are resistant to gamma/beta radiation and are highly selective for sodium ions. Potential applications include (1) caustic recycle for sludge leaching, regeneration of ion exchange resins, inhibition of corrosion in carbon steel tanks, or retrieval of tank wastes; (2) pH adjustment and reduction of competing cations to enhance cesium ion exchange processes; (3) sodium reduction in high-level waste sludges; and (4) sodium removal from acidic wastes to facilitate calcining. Initial experiments with dysprosium-based NaSICON membranes have demonstrated the feasibility of the process.

Kurath, D.E.; Hollenberg, G.W. [Pacific Northwest National Lab., Richland, WA (United States); Jue, Jan-Fong [Univ. of Utah, Salt Lake City, UT (United States)] [and others

1997-01-01

218

Salt splitting using ceramic membranes  

International Nuclear Information System (INIS)

[en] Inorganic ceramic membranes for salt splitting of radioactively contaminated sodium salt solutions are being developed for treating US Department of Energy tank wastes. The process consists of electrochemical separation of sodium ions from the salt solution using sodium (Na) Super Ion Conductors (NaSICON) membranes. In contrast to conventional organic-based bipolar or ion exchange membranes used in salt splitting, NaSICON membranes are resistant to gamma/beta radiation and are highly selective for sodium ions. Potential applications include (1) caustic recycle for sludge leaching, regeneration of ion exchange resins, inhibition of corrosion in carbon steel tanks, or retrieval of tank wastes; (2) pH adjustment and reduction of competing cations to enhance cesium ion exchange processes; (3) sodium reduction in high-level waste sludges; and (4) sodium removal from acidic wastes to facilitate calcining. Initial experiments with dysprosium-based NaSICON membranes have demonstrated the feasibility of the process

1997-01-01

219

Stability of split Stirling refrigerators  

International Nuclear Information System (INIS)

In many thermal systems spontaneous mechanical oscillations are generated under the influence of large temperature gradients. Well-known examples are Taconis oscillations in liquid-helium cryostats and oscillations in thermoacoustic systems. In split Stirling refrigerators the compressor and the cold finger are connected by a flexible tube. The displacer in the cold head is suspended by a spring. Its motion is pneumatically driven by the pressure oscillations generated by the compressor. In this paper we give the basic dynamic equations of split Stirling refrigerators and investigate the possibility of spontaneous mechanical oscillations if a large temperature gradient develops in the cold finger, e.g. during or after cool down. These oscillations would be superimposed on the pressure oscillations of the compressor and could ruin the cooler performance.

2009-02-01

220

Nogo receptor is involved in the adhesion of dendritic cells to myelin  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Nogo-66 receptor NgR1 and its structural homologue NgR2 are binding proteins for a number of myelin-associated inhibitory factors. After neuronal injury, these inhibitory factors are responsible for preventing axonal outgrowth via their interactions with NgR1 and NgR2 expressed on neurons. In vitro, cells expressing NgR1/2 are inhibited from adhering to and spreading on a myelin substrate. Neuronal injury also results in the presence of dendritic cells (DCs) in the central nervous system, where they can come into contact with myelin debris. The exact mechanisms of interaction of immune cells with CNS myelin are, however, poorly understood. Methods Human DCs were differentiated from peripheral blood monocytes and mouse DCs were differentiated from wild type and NgR1/NgR2 double knockout bone marrow precursors. NgR1 and NgR2 expression were determined with quantitative real time PCR and immunoblot, and adhesion of cells to myelin was quantified. Results We demonstrate that human immature myeloid DCs express NgR1 and NgR2, which are then down-regulated upon maturation. Human mature DCs also adhere to a much higher extent to a myelin substrate than immature DCs. We observe the same effect when the cells are plated on Nogo-66-His (binding peptide for NgR1), but not on control proteins. Mature DCs taken from Ngr1/2 knockout mice adhere to a much higher extent to myelin compared to wild type mouse DCs. In addition, Ngr1/2 knockout had no effect on in vitro DC differentiation or phenotype. Conclusions These results indicate that a lack of NgR1/2 expression promotes the adhesion of DCs to myelin. This interaction could be important in neuroinflammatory disorders such as multiple sclerosis in which peripheral immune cells come into contact with myelin debris.

McDonald Claire L; Steinbach Karin; Kern Florian; Schweigreiter Rüdiger; Martin Roland; Bandtlow Christine E; Reindl Markus

2011-01-01

 
 
 
 
221

MR imaging of the various stages of normal myelination during the first year of life  

International Nuclear Information System (INIS)

The normal process of myelination of the brain mainly occurs during the first year of life. This process as known from histology can be visualized by MRI. Because of the very long T1 and T2 of immature brain tissue it is necessary to use adjusted pulse sequences with a long TR in order to obtain sufficient tissue contrast. With long TR SE images five stages can be recognized in the process of normal myelination and brain maturation. During the first month of life long TR short TE SE images show what are believed to be myelinated structures by correlation with published histological studies with a high signal intensity, unmyelinated white matter with a low signal intensity and gray matter with an intermediate signal intensity. The signal intensity of unmyelinated and myelinated white matter is reversed on long TR long TE SE images. In the course of a few weeks the signal intensity of unmyelinated white matter becomes high and the signal intensity of myelinated white matter becomes low also on long TR short TE SE images. These changes are believed to be caused by a loss of water and a change in chemical composition of brain tissue just prior to the onset of a wave of myelination. With progression of myelination the signal intensity of white matter changes from high to intermediate to low. These changes result in stages of isointensity, first in the central parts of the brain, later in the lobar parts. At the end of the first year the adult contrast pattern is reached in all parts of the brain. IR images are also able to depict the progress of myelination, but appear to be less sensitive to subtle changes in the degree of myelination. The precise normal values for the five stages depend on the magnetic field strength and the pulse sequences used. (orig.)

1990-01-01

222

Astrocytes regulate myelin clearance through recruitment of microglia during cuprizone-induced demyelination.  

UK PubMed Central (United Kingdom)

Recent evidence suggests that astrocytes play an important role in regulating de- and remyelination in multiple sclerosis. The role of astrocytes is controversial, and both beneficial as well as detrimental effects are being discussed. We performed loss-of-function studies based on astrocyte depletion in a cuprizone-induced rodent model of demyelination. This led to strong astrogliosis accompanied by microgliosis and demyelination in C57BL/6 wild-type mice. Ablation of astrocytes in glial fibrillary acidic protein-thymidine kinase transgenic mice was associated with a failure of damaged myelin removal and a consecutive delay in remyelination. Despite oligodendrocyte death, myelin was still present, but ultrastructual investigations showed that the myelin structure was loosened and this damaged myelin did not protect axons. These alterations were associated with a decrease in microglial activation. Thus, our results show that astrocyte loss does not prevent myelin damage, but clearance of damaged myelin through recruitment of microglia is impaired. Further studies suggest that this process is regulated by the chemokine CXCL10. As a consequence of the delayed removal of myelin debris, remyelination and oligodendrocyte precursor cell proliferation were impaired. Experiments omitting the influence of myelin debris demonstrated an additional beneficial effect of astrocytes on oligodendrocyte regeneration during remyelination. In conclusion, these data demonstrate for the first time in vivo that astrocytes provide the signal environment that forms the basis for the recruitment of microglia to clear myelin debris, a process required for subsequent repair mechanisms. This is of great importance to understanding regenerative processes in demyelinating diseases such as multiple sclerosis.

Skripuletz T; Hackstette D; Bauer K; Gudi V; Pul R; Voss E; Berger K; Kipp M; Baumgärtner W; Stangel M

2013-01-01

223

Muscarinic receptor binding and muscarinic receptor-mediated inhibition of adenylate cyclase in rat brain myelin  

Energy Technology Data Exchange (ETDEWEB)

High-affinity muscarinic cholinergic receptors were detected in myelin purified from rat brain stem with use of the radioligands /sup 3/H-N-methylscopolamine (/sup 3/H-NMS), /sup 3/H-quinuclidinyl benzilate (/sup 3/H-QNB), and /sup 3/H-pirenzepine. /sup 3/H-NMS binding was also present in myelin isolated from corpus callosum. In contrast, several other receptor types, including alpha 1- and alpha 2-adrenergic receptors, present in the starting brain stem, were not detected in myelin. Based on Bmax values from Scatchard analyses, /sup 3/H-pirenzepine, a putative M1 selective ligand, bound to about 25% of the sites in myelin labeled by /sup 3/H-NMS, a nonselective ligand that binds to both M1 and M2 receptor subtypes. Agonist affinity for /sup 3/H-NMS binding sites in myelin was markedly decreased by Gpp(NH)p, indicating that a major portion of these receptors may be linked to a second messenger system via a guanine-nucleotide regulatory protein. Purified myelin also contained adenylate cyclase activity; this activity was stimulated several fold by forskolin and to small but significant extents by prostaglandin E1 and the beta-adrenergic agonist isoproterenol. Myelin adenylate cyclase activity was inhibited by carbachol and other muscarinic agonists; this inhibition was blocked by the antagonist atropine. Levels in myelin of muscarinic receptors were 20-25% and those of forskolin-stimulated adenylate cyclase 10% of the values for total particulate fraction of whole brain stem. These levels in myelin are appreciably greater than would be predicted on the basis of contamination. Also, additional receptors and adenylate cyclase, added by mixing nonmyelin tissue with whole brain stem, were quantitatively removed during the purification procedure.

Larocca, J.N.; Ledeen, R.W.; Dvorkin, B.; Makman, M.H.

1987-12-01

224

Empirical Methods for Compound Splitting  

CERN Multimedia

Compounded words are a challenge for NLP applications such as machine translation (MT). We introduce methods to learn splitting rules from monolingual and parallel corpora. We evaluate them against a gold standard and measure their impact on performance of statistical MT systems. Results show accuracy of 99.1% and performance gains for MT of 0.039 BLEU on a German-English noun phrase translation task.

Koehn, P; Koehn, Philipp; Knight, Kevin

2003-01-01

225

The Split Variational Inequality Problem  

CERN Multimedia

We propose a new variational problem which we call the Split Variational Inequality Problem (SVIP). It entails finding a solution of one Variational Inequality Problem (VIP), the image of which under a given bounded linear transformation is a solution of another VIP. We construct iterative algorithms that solve such problems, under reasonable conditions, in Hilbert space and then discuss special cases, some of which are new even in Euclidean space.

Censor, Yair; Reich, Simeon

2010-01-01

226

Split ring containment attachment device  

Energy Technology Data Exchange (ETDEWEB)

A containment attachment device is described for operatively connecting a glovebag to plastic sheeting covering hazardous material. The device includes an inner split ring member connected on one end to a middle ring member wherein the free end of the split ring member is inserted through a slit in the plastic sheeting to captively engage a generally circular portion of the plastic sheeting. A collar portion having an outer ring portion is provided with fastening means for securing the device together wherein the glovebag is operatively connected to the collar portion. Hazardous material such as radioactive waste may be sealed in plastic bags for small items or wrapped in plastic sheeting for large items. Occasionally the need arises to access the hazardous material in a controlled manner, that is, while maintaining total containment. Small items could be placed entirely inside a containment glovebag. However, it may not be possible or practical to place large items inside a containment; instead, one or more glovebags could be attached to the plastic sheeting covering the hazardous material. It is this latter application for which the split ring containment attachment device is intended.

Sammel, A.G.

1995-12-31

227

[Electron microscopic study of the chemical structural asymmetry of myelin sheaths  

UK PubMed Central (United Kingdom)

Osmium washing of ultrathin sections of the frog sciatic nerve myelin fibres performed with 4% acetic acid solution preceded their treatment with the Dragendorf solution and ammonium paramolibdate. This enabled us to localize amine and phosphate groups of myelin membranes. The data obtained suggest that the majority of phospholipids of these membranes are located on the cytoplasmic surfaces, whereas glycolipids and cholesterol--on the extracellular ones. Examination of these surfaces by freeze--fracturing revealed different hydratation degrees in these surfaces. These results show that myelin membranes are most convenient models for the study of structural and chemical asymmetry of biological membranes.

Korolev EV; Komissarchik IaIu; Filatov SE

1982-08-01

228

[Fluorescence anisotropy and the structure of myelin. I. The theory of the method  

UK PubMed Central (United Kingdom)

Theoretical aspects of the experiment dealing with measurements of fluorescence polarization degrees in stained myelinated nerve fibres are considered. Fluorescence polarization (FP) largely depends on the excitation azimuth, i.e. on the angle between the electrical vector of the polarized exciting light and the nerve fibre axis (geometrically it is a figure with the cylinder symmetry). The dependence of FP on the excitation azimuth is shown to be related to the degree of molecular orientation of dyes adsorbed on anisotropic layers of myelin membranes. This permits to associate FP with the structural changes of myelin membranes.

Gol'fand KA; Kaulin AB

1977-01-01

229

Compatibly Frobenius split subschemes are rigid  

CERN Multimedia

Schwede proved very recently in arXiv:0901.1154 that in a quasiprojective scheme X with a fixed Frobenius splitting, there are only finitely many subschemes {Y} that are compatibly split. (A simpler proof has already since been given in arXiv:0901.2098, by Kumar and Mehta.) It follows that their deformations (as compatibly split subschemes) are obstructed. We give a short proof that if X is projective, its compatibly split subschemes {Y} have no deformations at all (again, as compatibly split subschemes). This reproves Schwede's result in some simple cases.

Knutson, Allen

2009-01-01

230

Signalling Pathways that Inhibit the Capacity of Precursor Cells for Myelin Repair  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In demyelinating disorders such as Multiple Sclerosis (MS), targets of injury are myelin and oligodendrocytes, leading to severe neurological dysfunction. Regenerative therapies aimed at promoting oligodendrocyte maturation and remyelination are promising strategies for treatment in demyelinating di...

Jennifer K. Sabo; Holly S. Cate

231

The structural and functional role of myelin fast-migrating cerebrosides : pathological importance in multiple sclerosis  

DEFF Research Database (Denmark)

A family of neutral glycosphingolipids containing a 3-O-acetyl-sphingosine galactosylceramide (3-SAG) has been characterized. Seven new derivatives of galactosylceramide (GalCer), designated as fast-migrating cerebrosides (FMCs) by TLC retention factor, have been identified. The simplest compounds - FMC-1 and FMC-2 - of this series have been characterized as the 3-SAG containing nonhydroxy and hydroxy fatty acyl, respectively. The next two - FMC-3 and FMC-4 - add 6-O-acetyl-galactose and the most complex glycosphingolipids, FMC-5, -6 and -7, are 2,3,4,6-tetra-O-acetyl-3-SAG. These hydrophobic myelin lipid biomarkers coappear with GalCer during myelinogenesis and disappear along with GalCer in de- or dys-myelinating disorders. Myelin lipid antigens, including FMCs, are keys to myelin biology, opening the possibility of new and novel immune modulatory tools for treatment of autoimmune diseases including multiple sclerosis.

Podbielska, Maria; Levery, Steven B

2011-01-01

232

Lesioned corticospinal tract axons regenerate in myelin-free rat spinal cord  

Energy Technology Data Exchange (ETDEWEB)

In the adult central nervous system (CNS) of higher vertebrates lesioned axons seemed unable to regenerate and reach their former target regions due to influences of the CNS microenvironment. Evidence from in vitro and biochemical experiments has demonstrated the presence of inhibitory substrate components in CNS tissue, in particular in white matter. These CNS components, which strongly inhibit neurite growth, were identified as minor membrane proteins of defined molecular mass (35 and 250 kDa) in oligodendrocyte membranes and CNS myelin. Oligodendrocyte development and myelin formation can be prevented by x-irradiation of newborn rats. Here we show that in myelin-free spinal cords cortico-spinal tract fibers transected at 2 weeks of age show reelongation of many millimeters within 2-3 weeks after the lesion. In normally myelinated controls, regenerative sprouts grew less than 1.7 mm caudal to the lesion.

Savio, T.; Schwab, M.E. (Univ. of Zurich (Switzerland))

1990-06-01

233

Impact of human myelin on the maturation and function of human monocyte-derived dendritic cells.  

Science.gov (United States)

Macrophages and dendritic cells (DC) play an important role in the immunopathology of multiple sclerosis. We analyzed the impact of human myelin on monocyte-derived DC and describe their immunostimulatory capacity. Cells were grown on myelin and stimulated with LPS or a defined maturation cocktail. DC activation was analyzed by the expression of cell surface markers and the secretion of cytokines and chemokines. The immunostimulatory capacity of DC was assessed by allogeneic mixed-leukocyte reactions via proliferation. Additionally, their ability to bias T cells towards Th1, Th17 or Treg differentiation was investigated. We found that phagocytosis of myelin impaired the activation of DC, displayed by an impaired ability to stimulate allogeneic T cells, an increased production of TGF-beta1 and a diminished upregulation of CCR7 but did not affect the differentiation into T helper cell subsets. We hypothesize that myelin influences DC activation and plays a pivotal role in balancing immunity and tolerance. PMID:19945918

Gredler, Viktoria; Ebner, Susanne; Schanda, Kathrin; Forstner, Markus; Berger, Thomas; Romani, Nikolaus; Reindl, Markus

2009-11-28

234

Impact of human myelin on the maturation and function of human monocyte-derived dendritic cells.  

UK PubMed Central (United Kingdom)

Macrophages and dendritic cells (DC) play an important role in the immunopathology of multiple sclerosis. We analyzed the impact of human myelin on monocyte-derived DC and describe their immunostimulatory capacity. Cells were grown on myelin and stimulated with LPS or a defined maturation cocktail. DC activation was analyzed by the expression of cell surface markers and the secretion of cytokines and chemokines. The immunostimulatory capacity of DC was assessed by allogeneic mixed-leukocyte reactions via proliferation. Additionally, their ability to bias T cells towards Th1, Th17 or Treg differentiation was investigated. We found that phagocytosis of myelin impaired the activation of DC, displayed by an impaired ability to stimulate allogeneic T cells, an increased production of TGF-beta1 and a diminished upregulation of CCR7 but did not affect the differentiation into T helper cell subsets. We hypothesize that myelin influences DC activation and plays a pivotal role in balancing immunity and tolerance.

Gredler V; Ebner S; Schanda K; Forstner M; Berger T; Romani N; Reindl M

2010-03-01

235

Gestational nicotine exposure modifies myelin gene expression in the brains of adolescent rats with sex differences.  

UK PubMed Central (United Kingdom)

Myelination defects in the central nervous system (CNS) are associated with various psychiatric disorders, including drug addiction. As these disorders are often observed in individuals prenatally exposed to cigarette smoking, we tested the hypothesis that such exposure impairs central myelination in adolescence, an important period of brain development and the peak age of onset of psychiatric disorders. Pregnant Sprague Dawley rats were treated with nicotine (3?mg?kg(-1) per day; gestational nicotine (GN)) or gestational saline via osmotic mini pumps from gestational days 4-18. Both male and female offsprings were killed on postnatal day 35 or 36, and three limbic brain regions, the prefrontal cortex (PFC), caudate putamen and nucleus accumbens, were removed for measurement of gene expression and determination of morphological changes using quantitative real-time PCR (qRT-PCR) array, western blotting and immunohistochemical staining. GN altered myelin gene expression at both the mRNA and protein levels, with striking sex differences. Aberrant expression of myelin-related transcription and trophic factors was seen in GN animals, which correlated highly with the alterations in the myelin gene expression. These correlations suggest that these factors contribute to GN-induced alterations in myelin gene expression and also indicate abnormal function of oligodendrocytes (OLGs), the myelin-producing cells in the CNS. It is unlikely that these changes are attributable solely to an alteration in the number of OLGs, as the cell number was changed only in the PFC of GN males. Together, our findings suggest that abnormal brain myelination underlies various psychiatric disorders and drug abuse associated with prenatal exposure to cigarette smoke.

Cao J; Wang J; Dwyer JB; Gautier NM; Wang S; Leslie FM; Li MD

2013-01-01

236

Gestational nicotine exposure modifies myelin gene expression in the brains of adolescent rats with sex differences.  

Science.gov (United States)

Myelination defects in the central nervous system (CNS) are associated with various psychiatric disorders, including drug addiction. As these disorders are often observed in individuals prenatally exposed to cigarette smoking, we tested the hypothesis that such exposure impairs central myelination in adolescence, an important period of brain development and the peak age of onset of psychiatric disorders. Pregnant Sprague Dawley rats were treated with nicotine (3?mg?kg(-1) per day; gestational nicotine (GN)) or gestational saline via osmotic mini pumps from gestational days 4-18. Both male and female offsprings were killed on postnatal day 35 or 36, and three limbic brain regions, the prefrontal cortex (PFC), caudate putamen and nucleus accumbens, were removed for measurement of gene expression and determination of morphological changes using quantitative real-time PCR (qRT-PCR) array, western blotting and immunohistochemical staining. GN altered myelin gene expression at both the mRNA and protein levels, with striking sex differences. Aberrant expression of myelin-related transcription and trophic factors was seen in GN animals, which correlated highly with the alterations in the myelin gene expression. These correlations suggest that these factors contribute to GN-induced alterations in myelin gene expression and also indicate abnormal function of oligodendrocytes (OLGs), the myelin-producing cells in the CNS. It is unlikely that these changes are attributable solely to an alteration in the number of OLGs, as the cell number was changed only in the PFC of GN males. Together, our findings suggest that abnormal brain myelination underlies various psychiatric disorders and drug abuse associated with prenatal exposure to cigarette smoke. PMID:23591971

Cao, J; Wang, J; Dwyer, J B; Gautier, N M; Wang, S; Leslie, F M; Li, M D

2013-04-16

237

Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing- remitting multiple sclerosis.  

UK PubMed Central (United Kingdom)

BACKGROUND AND OBJECTIVE: Acute disseminated encephalomyelitis (ADEM) and relapsing-remitting multiple sclerosis (RRMS) share overlapping clinical, radiologic and laboratory features at onset. Because autoantibodies may contribute to the pathogenesis of both diseases, we sought to identify autoantibody biomarkers that are capable of distinguishing them. METHODS: We used custom antigen arrays to profile anti-myelin-peptide autoantibodies in sera derived from individuals with pediatric ADEM (n = 15), pediatric multiple sclerosis (Ped MS; n = 11) and adult MS (n = 15). Using isotype-specific secondary antibodies, we profiled both IgG and IgM reactivities. We used Statistical Analysis of Microarrays software to confirm the differences in autoantibody reactivity profiles between ADEM and MS samples. We used Prediction Analysis of Microarrays software to generate and validate prediction algorithms, based on the autoantibody reactivity profiles. RESULTS: ADEM was characterized by IgG autoantibodies targeting epitopes derived from myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein, and alpha-B-crystallin. In contrast, MS was characterized by IgM autoantibodies targeting myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein and oligodendrocyte-specific protein. We generated and validated prediction algorithms that distinguish ADEM serum (sensitivity 62-86%; specificity 56-79%) from MS serum (sensitivity 40-87%; specificity 62-86%) on the basis of combined IgG and IgM anti-myelin autoantibody reactivity to a small number of myelin peptides. CONCLUSIONS: Combined profiles of serum IgG and IgM autoantibodies identified myelin antigens that may be useful for distinguishing MS from ADEM. Further studies are required to establish clinical utility. Further biological assays are required to delineate the pathogenic potential of these antibodies.

Van Haren K; Tomooka BH; Kidd BA; Banwell B; Bar-Or A; Chitnis T; Tenembaum SN; Pohl D; Rostasy K; Dale RC; O'Connor KC; Hafler DA; Steinman L; Robinson WH

2013-04-01

238

Myelination and node of Ranvier formation on sensory neurons in a defined in vitro system.  

Science.gov (United States)

One of the most important developmental modifications of the nervous system is Schwann cell myelination of axons. Schwann cells ensheath axons to create myelin segments to provide protection to the axon as well as increase the conduction of action potentials. In vitro neuronal systems provide a unique modality to study a variety of factors influencing myelination as well as diseases associated with myelin sheath degradation. This work details the development of a patterned in vitro myelinating dorsal root ganglion culture. This defined system utilized a serum-free medium in combination with a patterned substrate, utilizing the cytophobic and cytophilic molecules (poly)ethylene glycol (PEG) and N-1[3 (trimethoxysilyl) propyl] diethylenetriamine (DETA), respectively. Directional outgrowth of the neurites and subsequent myelination was controlled by surface modifications, and conformity to the pattern was measured over the duration of the experiments. The myelinated segments and nodal proteins were visualized and quantified using confocal microscopy. This tissue-engineered system provides a highly controlled, reproducible model for studying Schwann cell interactions with sensory neurons, as well as the myelination process, and its effect on neuronal plasticity and peripheral nerve regeneration. It is also compatible for use in bio-hybrid constructs to reproduce the stretch reflex arc on a chip because the media combination used is the same that we have used previously for motoneurons, muscle, and for neuromuscular junction (NMJ) formation. This work could have application for the study of demyelinating diseases such as diabetes induced peripheral neuropathy and could rapidly translate to a role in the discovery of drugs promoting enhanced peripheral nervous system (PNS) remyelination. PMID:23949775

Rumsey, John W; McAleer, Christopher; Das, Mainak; Bhalkikar, Abhijeet; Wilson, Kerry; Stancescu, Maria; Lambert, Stephen; Hickman, James J

2013-08-16

239

[Antibody reaction to basic myelin proteins after intracisternal administration into animals  

UK PubMed Central (United Kingdom)

Pathogenetic properties of antibodies to main protein of myelin, which are responsible for initiation of demyelinization process in the central nervous system, are discussed. Development of the process is accompanied by alteration in a number of biochemical reactions. Effects of the antibodies to main protein of myelin, after their intracisternal administration, are considered in relation to activation of proteolysis, alteration of glycolipid content and the functional state of the brain.

Mendzheritski? AM

1984-09-01

240

Myelination and node of Ranvier formation on sensory neurons in a defined in vitro system.  

UK PubMed Central (United Kingdom)

One of the most important developmental modifications of the nervous system is Schwann cell myelination of axons. Schwann cells ensheath axons to create myelin segments to provide protection to the axon as well as increase the conduction of action potentials. In vitro neuronal systems provide a unique modality to study a variety of factors influencing myelination as well as diseases associated with myelin sheath degradation. This work details the development of a patterned in vitro myelinating dorsal root ganglion culture. This defined system utilized a serum-free medium in combination with a patterned substrate, utilizing the cytophobic and cytophilic molecules (poly)ethylene glycol (PEG) and N-1[3 (trimethoxysilyl) propyl] diethylenetriamine (DETA), respectively. Directional outgrowth of the neurites and subsequent myelination was controlled by surface modifications, and conformity to the pattern was measured over the duration of the experiments. The myelinated segments and nodal proteins were visualized and quantified using confocal microscopy. This tissue-engineered system provides a highly controlled, reproducible model for studying Schwann cell interactions with sensory neurons, as well as the myelination process, and its effect on neuronal plasticity and peripheral nerve regeneration. It is also compatible for use in bio-hybrid constructs to reproduce the stretch reflex arc on a chip because the media combination used is the same that we have used previously for motoneurons, muscle, and for neuromuscular junction (NMJ) formation. This work could have application for the study of demyelinating diseases such as diabetes induced peripheral neuropathy and could rapidly translate to a role in the discovery of drugs promoting enhanced peripheral nervous system (PNS) remyelination.

Rumsey JW; McAleer C; Das M; Bhalkikar A; Wilson K; Stancescu M; Lambert S; Hickman JJ

2013-08-01

 
 
 
 
241

Neuroglialpharmacology: Myelination As A Shared Mechanism of Action of Psychotropic Treatments  

Science.gov (United States)

Current psychiatric diagnostic schema segregate symptom clusters into discrete entities, however, large proportions of patients suffer from comorbid conditions that fit neither diagnostic nor therapeutic schema. Similarly, psychotropic treatments ranging from lithium and antipsychotics to serotonin reuptake inhibitors (SSRIs) and acetylcholinesterase inhibitors have been shown to be efficacious in a wide spectrum of psychiatric disorders ranging from autism, schizophrenia (SZ), depression, and bipolar disorder (BD) to Alzheimer’s disease (AD). This apparent lack of specificity suggests that psychiatric symptoms as well as treatments may share aspects of pathophysiology and mechanisms of action that defy current symptom-based diagnostic and neuron-based therapeutic schema. A myelin-centered model of human brain function can help integrate these incongruities and provide novel insights into disease etiologies and treatment mechanisms. Available data are integrated herein to suggest that widely used psychotropic treatments ranging from antipsychotics and antidepressants to lithium and electroconvulsive therapy share complex signaling pathways such as Akt and glycogen synthase kinase-3 (GSK3) that affect myelination, its plasticity, and repair. These signaling pathways respond to neurotransmitters, neurotrophins, hormones, and nutrition, underlie intricate neuroglial communications, and may substantially contribute to the mechanisms of action and wide spectra of efficacy of current therapeutics by promoting myelination. Imaging and genetic technologies make it possible to safely and noninvasively test these hypotheses directly in humans and can help guide clinical trial efforts designed to correct myelination abnormalities. Such efforts may provide insights into novel avenues for treatment and prevention of some of the most prevalent and devastating human diseases. Pervasive brain myelination underlies neural network synchrony and our distinctiveness as a species. Psychiatric diagnoses may share deficits in myelin development, plasticity, or repair. Treatments act on neuroglial signaling pathways such as Akt and GSK3 that improve myelination. Treatment efficacy may derive from myelination-driven improved neural network synchronization. “Neuroglialpharmacology” encapsulates a paradigm shift in medication development strategy.

Bartzokis, George

2013-01-01

242

Helical split ring french fry  

UK PubMed Central (United Kingdom)

A cut food piece formed in the shape of a helical split ring (10) by means of first cutting a slot in the whole food product by slot cutter (30) prior to urging the whole food product into engagement with cutter blade assembly (20) having wheel plate (21) rotating about central axis (23). Said cutter blade assembly (20) has a plurality of ring cutters (24) attached to and extending normally out from wheel plate (21) for cutting continuous concentric helical spirals in the whole food product. Shear blade (25) extends angularly out from wheel plate (21) for cutting concentric helical rings of food product off the whole food product.

MENDENHALL GEORGE A

243

Unstable split mode laser resonator  

International Nuclear Information System (INIS)

An unstable laser resonator system which provides an output beam with enhanced power, energy distribution and optical characteristics is disclosed. Two separate regions of gain medium each of which has the maximum dimensions permitted by the physical constraints of superfluorescent and excited population decay characteristics resonate in a split mode optical cavity having a common interlocked region of resonance which incorporates the contributions of each gain medium and combines the composite intracavity mode prior to output coupling from the resonator. The resonator system produces a coherent, phase-locked, high power, symmetric output beam. Optical cavities based on both spherical and cylindrical optics are discussed.

1975-01-01

244

Changes of magnetization transfer contrast of cerebral parenchyma during myelinating process in infants  

Energy Technology Data Exchange (ETDEWEB)

The myelinating processes are evaluated by spin echo MR images focused upon quantitative changes of myelin. The purpose of this study is to analyze a new method for the myelination using magnetization transfer ratios (MTRs) and calculated images. Thirty three newborns and infants (0 to 8 months) underwent MR study using gradient echo sequences with and without off-resonance pulse irradiation on a 1.5 T superconducting unit. The MTRs were measured in the internal capsula, genu and splenium of the corpus callosum, thalami, and putamina on the calculated images made out of two paired images. The MTRs in the white matter were lower than those of adult within 3 months and showed increase between 3 to 4 months followed by reaching the level of adult after 4 months. The gray matter represented similar MTR values as those of adult, however increased MTRs were also demonstrated between 3 to 4 months. As the white matter is composed of myelin which includes rich cholesterol, high MTRs in the white matter after 3 months suggested an increase of cholesterol and proportional changes between the lipid and cholesterol in the myelin. The gray matter also includes myelin components and it may reflect increasing of MTRs at the same period. (author)

Enomoto, Kyoko; Watabe, Tsuneya; Amanuma, Makoto; Heshiki, Atsuko [Saitama Medical School, Moroyama (Japan)

1997-03-01

245

Digital holographic microscopy of the myelin figure structural dynamics and the effect of thermal gradient.  

UK PubMed Central (United Kingdom)

Myelin figures (MFs) are cylindrical multilamellar lipid tubes that can be found in various healthy and diseased living cells. Their formation and dynamics involve some of the most mysterious configurations that lipid molecules can adopt under certain conditions. They have been studied with different microscopy methods. Due to the frequent coiling of their structure, the usual methods of microscopy fail to give precise quantitative information about their dynamics. In this paper, we introduced Digital Holographic Microscopy (DHM) as a useful method to calculate the precise dynamical volume, thickness, surface and length of the myelin figures. As an example of DHM imaging of myelin figures, their structure and growth rate in the presence and absence of temperature gradient have been studied in this work. We showed that the thickness of a myelin figure can be changed during the first few seconds. However, after approximately ten seconds, the thickness stabilizes and does not alter significantly. We further studied the effect of the thermal gradient on the length growth. The calculation of the length growth from the measurement of the myelin figure volume shows that the length (L) grows in time (t) as [Formula: see text]at the early stage of the myelin protrusion in both the presence and the absence of the thermal gradient. However, thermal gradient facilitates the growth and increases its rate.

Fathi N; Moradi AR; Habibi M; Vashaee D; Tayebi L

2013-06-01

246

Digital holographic microscopy of the myelin figure structural dynamics and the effect of thermal gradient.  

Science.gov (United States)

Myelin figures (MFs) are cylindrical multilamellar lipid tubes that can be found in various healthy and diseased living cells. Their formation and dynamics involve some of the most mysterious configurations that lipid molecules can adopt under certain conditions. They have been studied with different microscopy methods. Due to the frequent coiling of their structure, the usual methods of microscopy fail to give precise quantitative information about their dynamics. In this paper, we introduced Digital Holographic Microscopy (DHM) as a useful method to calculate the precise dynamical volume, thickness, surface and length of the myelin figures. As an example of DHM imaging of myelin figures, their structure and growth rate in the presence and absence of temperature gradient have been studied in this work. We showed that the thickness of a myelin figure can be changed during the first few seconds. However, after approximately ten seconds, the thickness stabilizes and does not alter significantly. We further studied the effect of the thermal gradient on the length growth. The calculation of the length growth from the measurement of the myelin figure volume shows that the length (L) grows in time (t) as [Formula: see text]at the early stage of the myelin protrusion in both the presence and the absence of the thermal gradient. However, thermal gradient facilitates the growth and increases its rate. PMID:23760951

Fathi, Narges; Moradi, Ali-Reza; Habibi, Mehdi; Vashaee, Daryoosh; Tayebi, Lobat

2013-05-24

247

Erythropoietin treatment alleviates ultrastructural myelin changes induced by murine cerebral malaria  

DEFF Research Database (Denmark)

BACKGROUND: Cerebral malaria (CM) is a severe complication of malaria with considerable mortality. In addition to acute encephalopathy, survivors frequently suffer from neurological sequelae. The pathogenesis is incompletely understood, hampering the development of an effective, adjunctive therapy, which is not available at present. Previously, erythropoietin (EPO) was reported to significantly improve the survival and outcome in a murine CM model. The study objectives were to assess myelin thickness and ultrastructural morphology in the corpus callosum in murine CM and to adress the effects of EPO treatment in this context. METHODS: The study consisted of two groups of Plasmodium berghei-infected mice and two groups of uninfected controls that were either treated with EPO or placebo (n?=?4 mice/group). In the terminal phase of murine CM the brains were removed and processed for electron microscopy. Myelin sheaths in the corpus callosum were analysed with transmission electron microscopy and stereology. RESULTS: The infection caused clinical CM, which was counteracted by EPO. The total number of myelinated axons was identical in the four groups and mice with CM did not have reduced mean thickness of the myelin sheaths. Instead, CM mice had significantly increased numbers of abnormal myelin sheaths, whereas EPO-treated mice were indistinguishable from uninfected mice. Furthermore, mice with CM had frequent and severe axonal injury, pseudopodic endothelial cells, perivascular oedemas and intracerebral haemorrhages. CONCLUSIONS: EPO treatment reduced clinical signs of CM and reduced cerebral pathology. Murine CM does not reduce the general thickness of myelin sheaths in the corpus callosum.

Hempel, Casper; Hyttel, Poul

2012-01-01

248

Central myelin gene expression during postnatal development in rats exposed to nicotine gestationally.  

UK PubMed Central (United Kingdom)

Abnormal myelin gene expression in the central nervous system (CNS) is associated with many mental illnesses, including psychiatric disorders and drug addiction. We have previously shown that prenatal exposure to nicotine, the major psychoactive component in cigarette smoke, alters myelin gene expression in the CNS of adolescent rats. To examine whether this effect is specific for adolescents, we examined myelin gene expression in the CNS of juveniles and adults. Pregnant Sprague-Dawley rats were treated with nicotine (3mg/kg/day; GN) or saline (GS) via osmotic mini pumps from gestational days 4 to 18. Both male and female offspring were sacrificed at postnatal day P20-21 (juveniles), P35-36 (adolescents), or P59-60 (adults). Three limbic brain regions, the prefrontal cortex (PFC), caudate putamen (CPu), and nucleus accumbens (NAc), were dissected. The expression of genes encoding major myelin components was evaluated using quantitative RT-PCR. We found that GN altered myelin gene expression in juveniles with brain region and sex differences. The pattern of alteration was different from that observed in adolescents. Although these genes were expressed normally in male adults, we observed decreased expression in GN-treated female adults, especially in the CPu. Thus, GN altered myelin gene expression throughout postnatal development and adulthood. The effect on adolescents was quite different from that at other ages, which correlated with the unique symptoms of many psychiatric disorders during adolescence.

Cao J; Dwyer JB; Gautier NM; Leslie FM; Ming DL

2013-08-01

249

Digital holographic microscopy of the myelin figure structural dynamics and the effect of thermal gradient  

Science.gov (United States)

Myelin figures (MFs) are cylindrical multilamellar lipid tubes that can be found in various healthy and diseased living cells. Their formation and dynamics involve some of the most mysterious configurations that lipid molecules can adopt under certain conditions. They have been studied with different microscopy methods. Due to the frequent coiling of their structure, the usual methods of microscopy fail to give precise quantitative information about their dynamics. In this paper, we introduced Digital Holographic Microscopy (DHM) as a useful method to calculate the precise dynamical volume, thickness, surface and length of the myelin figures. As an example of DHM imaging of myelin figures, their structure and growth rate in the presence and absence of temperature gradient have been studied in this work. We showed that the thickness of a myelin figure can be changed during the first few seconds. However, after approximately ten seconds, the thickness stabilizes and does not alter significantly. We further studied the effect of the thermal gradient on the length growth. The calculation of the length growth from the measurement of the myelin figure volume shows that the length (L) grows in time (t) as L?tat the early stage of the myelin protrusion in both the presence and the absence of the thermal gradient. However, thermal gradient facilitates the growth and increases its rate.

Fathi, Narges; Moradi, Ali-Reza; Habibi, Mehdi; Vashaee, Daryoosh; Tayebi, Lobat

2013-01-01

250

THE ANTI-AGING PROTEIN KLOTHO ENHANCES OLIGODENDROCYTE MATURATION AND MYELINATION OF THE CENTRAL NERVOUS SYSTEM  

Science.gov (United States)

We have previously shown that myelin abnormalities and loss characterize the normal aging process of the brain and that an age-associated reduction in Klotho is conserved across species. Predominantly generated in brain and kidney, Klotho overexpression extends life span, whereas loss of Klotho accelerates the development of aging-like phenotypes. While the function of Klotho in brain is unknown, loss of Klotho expression leads to cognitive deficits. In the present study, we found significant effects of Klotho on oligodendrocyte functions including induced maturation of rat primary oligodendrocytic progenitor cells (OPCs) in vitro and myelination. Phosphoprotein Western analysis indicated Klotho's downstream effects involve Akt and ERK signal pathways. Klotho increased OPCs maturation, and inhibition of Akt or ERK function blocked this effect on OPCs. In vivo studies of Klotho knockout mice and their control littermates revealed that knockout mice have a significant reduction in major myelin protein and gene expression. By immunohistochemistry, the number of total and mature oligodendrocytes was significantly lower in Klotho knockout mice. Strikingly, at the ultrastructural level, Klotho knockout mice exhibited significantly impaired myelination of the optic nerve and corpus callosum. These mice also displayed severe abnormalities at the nodes of Ranvier. In order to decipher the mechanisms by which Klotho affects oligodendrocytes, we used luciferase pathway reporters to identify the transcription factors involved. Taken together, these studies provide novel evidence for Klotho as a key player in myelin biology, which may thus be a useful therapeutic target in efforts to protect brain myelin against age-dependent changes.

Chen, Ci-Di; Sloane, Jacob A.; Li, Hu; Aytan, Nurgul; Giannaris, Eustathia L.; Zeldich, Ella; Hinman, Jason D.; Dedeoglu, Alpaslan; Rosene, Douglas L.; Bansal, Rashmi; Luebke, Jennifer; Kuro-o, Makoto; Abraham, Carmela R.

2013-01-01

251

Tricarboxilyc acid cycle-sustained oxidative phosphorylation in isolated myelin vesicles.  

UK PubMed Central (United Kingdom)

The Central Nervous System (CNS) function was shown to be fuelled exclusively by oxidative phosphorylation (OXPHOS). This is in line with the sensitivity of brain to hypoxia, but less with the scarcity of the mitochondria in CNS. Consistently with the ectopic expression of FoF1-ATP synthase and the electron transfer chain in myelin, we have reported data demonstrating that isolated myelin vesicles (IMV) conduct OXPHOS. It may suggest that myelin sheath could be a site for the whole aerobic degradation of glucose. In this paper, we assayed the functionality of glycolysis and of TCA cycle enzymes in IMV purified from bovine forebrain. We found the presence and activity of all of the glycolytic and TCA cycle enzymes, comparable to those in mitochondria-enriched fractions, in the same experimental conditions. IMV also contain consistent carbonic anhydrase activity. The complex of data suggest that myelin may be a contributor in energy supply for the axon, performing an extra-mitochondrial aerobic OXPHOS. The vision of myelin as the site of aerobic metabolism may shed a new light on many demyelinating pathologies, that cause an a yet unresolved axonal degeneration and whose clinical onset coincides with myelin development completion.

Ravera S; Bartolucci M; Calzia D; Aluigi MG; Ramoino P; Morelli A; Panfoli I

2013-07-01

252

Damage to Myelin and Oligodendrocytes: A Role in Chronic Outcomes Following Traumatic Brain Injury?  

Directory of Open Access Journals (Sweden)

Full Text Available There is increasing evidence in the experimental and clinical traumatic brain injury (TBI) literature that loss of central myelinated nerve fibers continues over the chronic post-traumatic phase after injury. However, the biomechanism(s) of continued loss of axons is obscure. Stretch-injury to optic nerve fibers in adult guinea-pigs was used to test the hypothesis that damage to the myelin sheath and oligodendrocytes of the optic nerve fibers may contribute to, or facilitate, the continuance of axonal loss. Myelin dislocations occur within internodal myelin of larger axons within 1–2 h of TBI. The myelin dislocations contain elevated levels of free calcium. The volume of myelin dislocations increase with greater survival and are associated with disruption of the axonal cytoskeleton leading to secondary axotomy. Waves of Ca2+ depolarization or spreading depression extend from the initial locus injury for perhaps hundreds of microns after TBI. As astrocytes and oligodendrocytes are connected via gap junctions, it is hypothesized that spreading depression results in depolarization of central glia, disrupt axonal ionic homeostasis, injure axonal mitochondria and allow the onset of axonal degeneration throughout an increasing volume of brain tissue; and contribute toward post-traumatic continued loss of white matter.

William L. Maxwell

2013-01-01

253

Gluon splitting in a shockwave  

Science.gov (United States)

The study of azimuthal correlations in particle production at forward rapidities in proton-nucleus collisions provides direct information about high gluon density effects, like gluon saturation, in the nuclear wavefunction. In the kinematical conditions for proton-lead collisions at the LHC, the forward di-hadron production is dominated by partonic processes in which a gluon from the proton splits into a pair of gluons, while undergoing multiple scattering off the dense gluon system in the nucleus. We compute the corresponding cross-section using the Colour Glass Condensate effective theory, which enables us to include the effects of multiple scattering and gluon saturation in the leading logarithmic approximation at high energy. This opens the way towards systematic studies of angular correlations in two-gluon production, similar to previous studies for quark-gluon production in the literature. We consider in more detail two special kinematical limits: the "back-to-back correlation limit", where the transverse momenta of the produced gluons are much larger than the nuclear saturation momentum, and the "double parton scattering limit", where the two gluons are produced by a nearly collinear splitting occurring prior to the collision. We argue that saturation effects remain important even for relatively high transverse momenta (i.e. for nearly back-to-back configurations), leading to geometric scaling in the azimuthal distribution.

Iancu, E.; Laidet, J.

2013-10-01

254

Split-mode ultrasonic transducer.  

UK PubMed Central (United Kingdom)

A split-mode ultrasonic transducer is investigated in both theory and experiment. This transducer is a two-dimensional structure of periodically poled domains in a ferroelectric wafer with free surfaces. The acoustic vibrations are excited by a radio frequency electric current applied along the length of the wafer, which allows the basal-plane surfaces to be free of metal coatings and thus ready for further biomedical applications. A specific physical property of this transducer consists of the multiple acousto-electric resonances, which occur due to an acoustic mode split when the acoustic half-wavelength is equal to the domain length. Possible applications include ultrasonic generation and detection at the micro-scale, intravascular sonification and visualization, ultrasound therapy of localized small areas such as the eye, biomedical applications for cell cultures, and traditional nondestructive testing including bones and tissues. A potential use of a non-metallized wafer is a therapeutic application with double action that is both ultrasound itself and an electric field over the wafer. The experimental measurements and theoretical calculations are in good agreement.

Ostrovskii I; Cremaldi L

2013-08-01

255

Radioimmunoassay of myelin basic protein. A methodological evaluation  

Energy Technology Data Exchange (ETDEWEB)

Three techniques for separating free antigen from antigen-antibody complexes have been applied to radioimmunoassay of myelin basic protein: cold ethanol precipitation of complexes, dextran-coated charcoal precipitation of free antigen, and second antibody precipitation of complexes. After optimization of the incubation and separation steps, the 3 methods were evaluated for precision and accuracy when applied to both spinal fluid and brain tissue homogenates. For determinations in brain tissue all 3 methods showed the same precision and gave largely the same values, though the ethanol method gave slightly lower levels. For spinal fluid the ethanol and dextran-charcoal methods gave the same values, but the double antibody method gave values only 1/3 as high. With spinal fluid, the precision of the dextran-charcoal method was poor compared with that of the other two. The double antibody method proved to be the method of choice for brain tissue samples, when the results of the incubation and separation steps, and the precision and accuracy of the determinations were taken into account. However, for an unknown reason values for spinal fluid were too low by this method. Therefore the ethanol precipitation method is recommended for spinal fluid samples and the double antibody method for brain tissue samples.

Karlsson, B.; Alling, C. (Department of Psychiatry and Neurochemistry, University of Goeteborg, St. Joergen Hospital, Hisings Backa, Sweden)

1982-11-26

256

Iterative Splitting Methods for Differential Equations  

CERN Document Server

Iterative Splitting Methods for Differential Equations explains how to solve evolution equations via novel iterative-based splitting methods that efficiently use computational and memory resources. It focuses on systems of parabolic and hyperbolic equations, including convection-diffusion-reaction equations, heat equations, and wave equations. In the theoretical part of the book, the author discusses the main theorems and results of the stability and consistency analysis for ordinary differential equations. He then presents extensions of the iterative splitting methods to partial differential

Geiser, Juergen

2011-01-01

257

Splittings of Non-Finitely Generated Groups  

CERN Multimedia

Niblo, Sageev, Scott, and Swarup made constructions for a finite collection of almost invariant sets over finitely generated subgroups of a finitely generated group. I modify the constructions to work without any finite generation assumptions, instead assuming that the almost invariant sets come from splittings. The results include symmetry of crossing and intersection number, showing that splittings are automatically in good position, putting splittings in very good position using a "minimal" cubing, and using the same cubing to construct an algebraic regular neighborhood.

Lassonde, Robin M

2011-01-01

258

Tube splitting furnace surrounded by cylindrical jacket  

International Nuclear Information System (INIS)

The application concerns a methane splitting plant, in which heat generated in a nuclear reactor is used directly, without an intermediate circuit in a process requiring heat, i.e. a CH4/H2O mixture is split into H2, CO and CO2 by supplying heat and using a catalyst. This split gas is used as heat carrier in transport of the heat energy obtained in a high temperature reactor to a remote energy consumption location, where the split gas is again converted to methane by catalysis and the heat released is used. The methane splitting furnace is a tall vertical cylinder, which contains 313 splitting tubes. The helium coming from the high temperature reactor reaches the cylinder from below at 9500C and 39 bar, and gives up heat to the splitting tubes projecting down from above; it is taken away at 8000C and is taken to the steam raising unit and the blower after it. The helium is returned from the blower at 3000C and is taken through an annular space above the hot gas space mentioned above, in order to cool the support plate for the splitting tubes above it. From here, the cold helium returns to the high temperature reactor. The CH4/H2O mixture enters the space above the support plate at 5000C and 44 bar, where it is distributed to the individual splitting tubes. It flows down in these, where it is split into H2, CO and CO2 by hot helium using a catalytic effect. The split gas flows upwards through the coaxial return pipes in the splitting tubes, where it is collected in a space above the gas mixture distribution space and is returned to the remote gas pipe at 6800C. (RB)

1976-04-06

259

Stabilizations of Heegaard splittings of graph manifolds  

CERN Document Server

We show that after one stabilization, a strongly irreducible Heegaard splitting of suitably large genus of a graph manifold is isotopic to an amalgamation along a modified version of the system of canonical tori in the JSJ decomposition. As a corollary, two strongly irreducible Heegaard splittings of a graph manifold of suitably large genus are isotopic after at most one stabilization of the higher genus splitting.

Derby-Talbot, R

2006-01-01

260

Crystal structure of the extracellular domain of human myelin protein zero  

Energy Technology Data Exchange (ETDEWEB)

Charcot-Marie-Tooth disease (CMT), a hereditary motor and sensory neuropathy, is the most common genetic neuropathy with an incidence of 1 in 2600. Several forms of CMT have been identified arising from different genomic abnormalities such as CMT1 including CMT1A, CMT1B, and CMTX. CMT1 with associated peripheral nervous system (PNS) demyelination, the most frequent diagnosis, demonstrates slowed nerve conduction velocities and segmental demyelination upon nerve biopsy. One of its subtypes, CMT1A, presents a 1.5-Mb duplication in the p11-p12 region of the human chromosome 17 which encodes peripheral myelin protein 22 (PMP22). CMT1B, a less common form, arises from the mutations in the myelin protein zero (MPZ) gene on chromosome 1, region q22-q23, which encodes the major structural component of the peripheral myelin. A rare type of CMT1 has been found recently and is caused by point mutations in early growth response gene 2 (EGR2), encoding a zinc finger transcription factor in Schwann cells. In addition, CMTX, an X-linked form of CMT, arises from a mutation in the connexin-32 gene. Myelin protein zero, associated with CMT1B, is a transmembrane protein of 219 amino acid residues. Human MPZ consists of three domains: 125 residues constitute the glycosylated immunoglobulin-like extracellular domain; 27 residues span the membrane; and 67 residues comprise the highly basic intracellular domain. MPZ makes up approximately 50% of the protein content of myelin, and is expressed predominantly in Schwann cells, the myelinating cell of the PNS. Myelin protein zero, a homophilic adhesion molecule, is a member of the immunoglobulin super-family and is essential for normal myelin structure and function. In addition, MPZ knockout mice displayed abnormal myelin that severely affects the myelination pathway, and overexpression of MPZ causes congenital hypomyelination of peripheral nerves. Myelin protein zero mutations account for {approx}5% of patients with CMT. To date, over 125 different mutations in the MPZ gene leading to peripheral neuropathy in patients have been reported worldwide (http://www.molgen. ua.ac.be/CMTMutations). All identified mutations resulting in a change or deletion of amino acid residues in MPZ give rise to neuropathy with the exception of R215L, which instead causes a benign polymorphism. Furthermore, more detailed analysis has classified the MPZ mutations into two major groups. In the first group, the mutations disrupt the intracellular processing of MPZ and are primarily associated with early onset neuropathy. It has been proposed that the mutated MPZ is trapped inside the cell rather than being transported to the plasma membrane. However, other evidence suggests that the mutated MPZ protein is expressed on the plasma membrane, but dominant-negatively disrupts the structure of myelin. In the second group, the MPZ mutations are associated with late onset neuropathy as these mutations cause only mild demyelination. The underlying mechanism is elusive with the hypothesis being that the second group of mutations cause minor abnormalities in the myelin sheath that over time may lead to aberrant Schwann cell-axon interactions and subsequently to axonal degeneration. The crystal structure of the extracellular domain of human MPZ (hP0ex) fused with maltose binding protein (MBP) is reported at 2.1 {angstrom} resolution. While the crystal structure of rat MPZ extracellular domain (rP0ex) is available, the crystal structure of the human counterpart is useful for the analysis of the two homologs as well as a comparison between the two species. The hP0ex molecule reveals subtle structural variations between two homologs allowing comparison of the human myelin protein zero to that of the rat protein. The alignment of these homologs is shown in Figure 1(a).

Liu, Zhigang; Wang, Yong; Yedidi, Ravikiran S.; Brunzelle, Joseph S.; Kovari, Iulia A.; Sohi, Jasloveleen; Kamholz, John; Kovari, Ladislau C. (WSU-MED); (NWU)

2012-03-27

 
 
 
 
261

Zeeman splitting in ballistic hole quantum wires  

CERN Multimedia

We have studied the Zeeman splitting in ballistic hole quantum wires formed in a (311)A quantum well by surface gate confinement. Transport measurements clearly show lifting of the spin degeneracy and crossings of the subbands when an in-plane magnetic field B is applied parallel to the wire. When B is oriented perpendicular to the wire, no spin-splitting is discernible up to B = 8.8 T. The observed large Zeeman splitting anisotropy in our hole quantum wires demonstrates the importance of quantum-confinement for spin-splitting in nanostructures with strong spin-orbit coupling.

Danneau, R; Clarke, W R; Ho, L H; Micolich, A P; Simmons, M Y; Hamilton, A R; Pepper, M; Ritchie, D A; Zülicke, U

2006-01-01

262

[Therapeutic effect of myelin basic protein and synthetic encephalitogenic peptide in guinea pigs with experimental allergic encephalomyelitis  

UK PubMed Central (United Kingdom)

Effect of antigenic factors of experimental allergic encephalomyelitis (alkaline protein of myelin and synthetic encephalitogenic peptide) was studied in guinea pigs with distinct manifestations of the experimental allergic encephalomyelitis. The animals recovered after prolonged administration of alkaline protein of myelin within 14 days, if they were sensibilized either by bovine alkaline protein of myelin or by synthetic encephalitogenic peptide. Synthetic encephalitogenic peptide was only effective in treatment of the disease caused by the peptide.

Belik IaV; Terletskaia IaT; Kozulina EP; Syrovatskaia LP; Gershkovich AA

1978-05-01

263

Pneumatically controlled split cycle cooler  

Energy Technology Data Exchange (ETDEWEB)

A pneumatically controlled split cycle cooler utilizes a dual piston compressor in conjunction with a remotely positioned head, the dual pistons are angularly spaced to provide in phase and out of phase pressure pulses for the head; and the head includes a pneumatic piston having an upwardly extending stem to which is attached a displacer/regenerator, a coldfinger, and a pair of pressure volumes spaced above and below the piston by seals and a pneumatic dampening volume between the seals, said pressure volumes operatively connected to the dual pistons for adding and subtracting their pressures in a complementary manner for proper timing and location of the displacer/regenerator and said pneumatic dampening volume operative to provide a pneumatic dampening of the piston to prevent the displacer/regenerator from striking the ends of the cooler and creating audible noise and microphonic inputs to a load to be cooled.

Taylor Sr., C. O.

1985-07-02

264

Gluon splitting in a shockwave  

CERN Document Server

The study of azimuthal correlations in particle production at forward rapidities in proton-nucleus collisions provides direct information about high gluon density effects, like gluon saturation, in the nuclear wavefunction. In the kinematical conditions for proton-lead collisions at the LHC, the forward di-hadron production is dominated by partonic processes in which a gluon from the proton splits into a pair of gluons, while undergoing multiple scattering off the dense gluon system in the nucleus. We compute the corresponding cross-section using the Colour Glass Condensate effective theory, which enables us to include the effects of multiple scattering and gluon saturation in the leading logarithmic approximation at high energy. This opens the way towards systematic studies of angular correlations in two-gluon production, similar to previous studies for quark-gluon production in the literature. We consider in more detail two special kinematical limits: the "back-to-back correlation limit", where the transver...

Iancu, Edmond

2013-01-01

265

Dark matter from split seesaw  

International Nuclear Information System (INIS)

The seesaw mechanism in models with extra dimensions is shown to be generically consistent with a broad range of Majorana masses. The resulting democracy of scales implies that the seesaw mechanism can naturally explain the smallness of neutrino masses for an arbitrarily small right-handed neutrino mass. If the scales of the seesaw parameters are split, with two right-handed neutrinos at a high scale and one at a keV scale, one can explain the matter-antimatter asymmetry of the universe, as well as dark matter. The dark matter candidate, a sterile right-handed neutrino with mass of several keV, can account for the observed pulsar velocities and for the recent data from Chandra X-ray Observatory, which suggest the existence of a 5 keV sterile right-handed neutrino.

2010-09-27

266

Salt splitting with ceramic membranes  

Energy Technology Data Exchange (ETDEWEB)

The purpose of this task is to develop ceramic membrane technologies for salt splitting of radioactively contaminated sodium salt solutions. This technology has the potential to reduce the low-level waste (LLW) disposal volume, the pH and sodium hydroxide content for subsequent processing steps, the sodium content of interstitial liquid in high-level waste (HLW) sludges, and provide sodium hydroxide free of aluminum for recycle within processing plants at the DOE complex. Potential deployment sites include Hanford, Savannah River, and Idaho National Engineering Laboratory (INEL). The technical approach consists of electrochemical separation of sodium ions from the salt solution using sodium (Na) Super Ion Conductors (NaSICON). As the name implies, sodium ions are transported rapidly through these ceramic crystals even at room temperatures.

Kurath, D. [Pacific Northwest National Lab., Richland, WA (United States)

1996-10-01

267

Salt splitting with ceramic membranes  

International Nuclear Information System (INIS)

[en] The purpose of this task is to develop ceramic membrane technologies for salt splitting of radioactively contaminated sodium salt solutions. This technology has the potential to reduce the low-level waste (LLW) disposal volume, the pH and sodium hydroxide content for subsequent processing steps, the sodium content of interstitial liquid in high-level waste (HLW) sludges, and provide sodium hydroxide free of aluminum for recycle within processing plants at the DOE complex. Potential deployment sites include Hanford, Savannah River, and Idaho National Engineering Laboratory (INEL). The technical approach consists of electrochemical separation of sodium ions from the salt solution using sodium (Na) Super Ion Conductors (NaSICON). As the name implies, sodium ions are transported rapidly through these ceramic crystals even at room temperatures

1996-01-01

268

Spherical splitting of 3-orbifolds  

CERN Multimedia

The famous Haken-Kneser-Milnor theorem states that every 3-manifold can be expressed in a unique way as a connected sum of prime 3-manifolds. The analogous statement for 3-orbifolds has been part of the folklore for several years, and it was commonly believed that slight variations on the argument used for manifolds would be sufficient to establish it. We demonstrate in this paper that this is not the case, proving that the apparently natural notion of ``essential'' system of spherical 2-orbifolds is not adequate in this context. We also show that the statement itself of the theorem must be given in a substantially different way. We then prove the theorem in full detail, using a certain notion of ``efficient splitting system.''

Petronio, C

2004-01-01

269

Impairment of heme synthesis in myelin as potential trigger of multiple sclerosis.  

UK PubMed Central (United Kingdom)

The pathogenesis of multiple sclerosis (MS), a disease characterized by demyelination and subsequent axonal degeneration, is as yet unknown. Also, the nature of the disease is as yet not established, since doubts have been cast on its autoimmune origin. Genetic and environmental factors have been implied in MS, leading to the idea of an overall multifactorial origin. An unexpected role in energizing the axon has been reported for myelin, supposed to be the site of consumption of most of oxygen in brain. Myelin would be able to perform oxidative phosphorylation to supply the axons with ATP, thanks to the expression therein of mitochondrial F(o)F(1)-ATP synthase, and respiratory chains. Interestingly, myelin expresses the pathway of heme synthesis, hence of cytochromes, that rely on heme group, in turn depending on Fe availability. Poisoning by these pollutants shares the common characteristic to bring about demyelination both in animal models and in man. Carbon monoxide (CO) and lead poisoning which cause functional imbalance of the heme group, as well as of heme synthesis, cause myelin damage. On the other hand, a lack of essential metals such as iron and copper, produces dramatic myelin decrease. Myelin is a primary target, of iron shortage, indicating that in myelin Fe-dependent processes are more active than in other tissues. The predominant spread of MS in industrialized countries where pollution by heavy metals, and CO poisoning is widespread, suggests a relationship among toxic action of metal pollutants and MS. According to the present hypothesis, MS can be primarily triggered by environmental factors acting on a genetic susceptibility, while the immune response may be a consequence of a primary oxidative damage due to reactive oxygen species produced consequently to an imbalance of cytochromes and respiratory chains in the sheath.

Morelli A; Ravera S; Calzia D; Panfoli I

2012-06-01

270

Retinal axon regeneration in the lizard Gallotia galloti in the presence of CNS myelin and oligodendrocytes.  

Science.gov (United States)

Retinal ganglion cell (RGC) axons in lizards (reptiles) were found to regenerate after optic nerve injury. To determine whether regeneration occurs because the visual pathway has growth-supporting glia cells or whether RGC axons regrow despite the presence of neurite growth-inhibitory components, the substrate properties of lizard optic nerve myelin and of oligodendrocytes were analyzed in vitro, using rat dorsal root ganglion (DRG) neurons. In addition, the response of lizard RGC axons upon contact with rat and reptilian oligodendrocytes or with myelin proteins from the mammalian central nervous system (CNS) was monitored. Lizard optic nerve myelin inhibited extension of rat DRG neurites, and lizard oligodendrocytes elicited DRG growth cone collapse. Both effects were partially reversed by antibody IN-1 against mammalian 35/250 kD neurite growth inhibitors, and IN-1 stained myelinated fiber tracts in the lizard CNS. However, lizard RGC growth cones grew freely across oligodendrocytes from the rat and the reptilian CNS. Mammalian CNS myelin proteins reconstituted into liposomes and added to elongating lizard RGC axons caused at most a transient collapse reaction. Growth cones always recovered within an hour and regrew. Thus, lizard CNS myelin and oligodendrocytes possess nonpermissive substrate properties for DRG neurons--like corresponding structures and cells in the mammalian CNS, including mammalian-like neurite growth inhibitors. Lizard RGC axons, however, appear to be far less sensitive to these inhibitory substrate components and therefore may be able to regenerate through the visual pathway despite the presence of myelin and oligodendrocytes that block growth of DRG neurites. PMID:9562185

Lang, D M; Monzón-Mayor, M; Bandtlow, C E; Stuermer, C A

1998-05-01

271

Deletion of a splicing enhancer disrupts PLP1/DM20 ratio and myelin stability.  

UK PubMed Central (United Kingdom)

PLP1 and DM20, major myelin proteins, are generated by developmentally regulated alternative splicing. In the post-natal brain, PLP1 is the predominant product. Deletion of a splicing enhancer in PLP1 intron 3 causes a mild form of Pelizaeus-Merzbacher disease and reduces PLP1 specific splicing in vitro (Hobson, G. M., Huang, Z., Sperle, K., Stabley, D. L., Marks, H. G., and Cambi, F., 2002. A PLP splicing abnormality is associated with an unusual presentation of PMD. Ann. Neurol. 52, 477-488). We sought to investigate the pathogenic role of the mutation and to determine the consequences on the developmental regulation of PLP1 alternative splicing and myelin stability and function in vivo. We have generated a knockin mouse that carries deletion of the intronic splicing enhancer and have characterized the PLP1/DM20 ratio by Real Time RT-PCR and Western blot analysis in the developing and mature brain and examined the clinical and pathological phenotype by motor testing and electron microscopy. The deletion impairs the increase in the PLP1/DM20 transcript and protein ratio at the time of myelination and in adulthood and results in a PLP1 hypomorph. Electron microscopy shows abnormal myelin wraps with fragmented myelin whorls, which are progressive with age, suggesting a defect in myelin stability. Phenotypic characterization of the knockin mouse shows a defect in motor coordination. The data indicate that the intronic splicing enhancer is necessary for the developmental increase in PLP1/DM20 ratio and that full PLP1 dosage is necessary for myelin stability and brain function. This knockin mouse represents a useful model to investigate the mechanisms of disease in human disorders in which PLP1 expression is reduced.

Wang E; Dimova N; Sperle K; Huang Z; Lock L; McCulloch MC; Edgar JM; Hobson GM; Cambi F

2008-12-01

272

Salt splitting using ceramic membranes  

Energy Technology Data Exchange (ETDEWEB)

Many radioactive aqueous wastes in the DOE complex have high concentrations of sodium that can negatively affect waste treatment and disposal operations. Sodium can decrease the durability of waste forms such as glass and is the primary contributor to large disposal volumes. Waste treatment processes such as cesium ion exchange, sludge washing, and calcination are made less efficient and more expensive because of the high sodium concentrations. Pacific Northwest National Laboratory (PNNL) and Ceramatec Inc. (Salt Lake City UT) are developing an electrochemical salt splitting process based on inorganic ceramic sodium (Na), super-ionic conductor (NaSICON) membranes that shows promise for mitigating the impact of sodium. In this process, the waste is added to the anode compartment, and an electrical potential is applied to the cell. This drives sodium ions through the membrane, but the membrane rejects most other cations (e.g., Sr{sup +2}, Cs{sup +}). The charge balance in the anode compartment is maintained by generating H{sup +} from the electrolysis of water. The charge balance in the cathode is maintained by generating OH{sup {minus}}, either from the electrolysis of water or from oxygen and water using an oxygen cathode. The normal gaseous products of the electrolysis of water are oxygen at the anode and hydrogen at the cathode. Potentially flammable gas mixtures can be prevented by providing adequate volumes of a sweep gas, using an alternative reductant or destruction of the hydrogen as it is generated. As H{sup +} is generated in the anode compartment, the pH drops. The process may be operated with either an alkaline (pH>12) or an acidic anolyte (pH <1). The benefits of salt splitting using ceramic membranes are (1) waste volume reduction and reduced chemical procurement costs by recycling of NaOH; and (2) direct reduction of sodium in process streams, which enhances subsequent operations such as cesium ion exchange, calcination, and vitrification.

Kurath, D.E. [Pacific Northwest National Lab., Richland, WA (United States)

1997-10-01

273

Translation of myelin basic protein mRNA in oligodendrocytes is regulated by integrin activation and hnRNP-K  

DEFF Research Database (Denmark)

Myelination in the central nervous system provides a unique example of how cells establish asymmetry. The myelinating cell, the oligodendrocyte, extends processes to and wraps multiple axons of different diameter, keeping the number of wraps proportional to the axon diameter. Local regulation of protein synthesis represents one mechanism used to control the different requirements for myelin sheath at each axo–glia interaction. Prior work has established that ?1-integrins are involved in the axoglial interactions that initiate myelination. Here, we show that integrin activation regulates translation of a key sheath protein, myelin basic protein (MBP), by reversing the inhibitory effect of the mRNA 3?UTR. During oligodendrocyte differentiation and myelination ?6?1-integrin interacts with hnRNP-K, an mRNA-binding protein, which binds to MBP mRNA and translocates from the nucleus to the myelin sheath. Furthermore, knockdown of hnRNP-K inhibits MBP protein synthesis during myelination. Together, these results identify a novel pathway by which axoglial adhesion molecules coordinate MBP synthesis with myelin sheath formation

Laursen, Lisbeth Schmidt; Chan, Colin W

2011-01-01

274

Characterization of dodecylphosphocholine/myelin basic protein complexes  

Energy Technology Data Exchange (ETDEWEB)

The stoichiometry of myelin basic protein (MBP)/dodecylphosphocholine (DPC) complexes and the location of protein segments in the micelle have been investigated by electron paramagnetic resonance (EPR), ultracentrifugation, photon correlation light scattering, /sup 31/P, /sup 13/C, and /sup 1/H nuclear magnetic resonance (NMR), and electron microscopy. Ultracentrifugation measurements indicate that MBP forms stoichiometrically well-defined complexes consisting of 1 protein molecule and approximately 140 detergent molecules. The spin-labels 5-, 12-, and 16-doxylstearate have been incorporated into DPC/MBP aggregates. EPR spectral parameters and /sup 13/C and /sup 1/H NMR relaxation times indicate that the addition of MBP does not affect the environment and location of the labels or the organization of the micelles except for a slight increase in size. Previous results indicating that the protein lies primarily near the surface of the micelle have been confirmed by comparing /sup 13/C NMR spectra of the detergent with and without protein with spectra of protein/detergent aggregates containing spin-labels. Electron micrographs of the complexes taken by using the freeze-fracture technique confirm that the estimated size obtained by light-scattering measurements. Overall, these results indicate that mixtures of MBP and DPC can form highly porous particles with well-defined protein and lipid stoichiometry. The structural integrity of these particles appears to be based on protein-lipid interactions. In addition, electron micrographs of aqueous DPC/MBP suspensions show the formation of a small amount of material consisting of large arrays of detergent micelles, suggesting that MBP is capable of inducing large changes in the overall organization of the detergent.

Mendz, G.L.; Moore, W.J.; Kaplin, I.J.; Cornell, B.A.; Separovic, F.; Miller, D.J.; Brown, L.R.

1988-01-12

275

Prevalence of myelinated retinal nerve fibres in adult Indians: the Central India Eye and Medical Study.  

UK PubMed Central (United Kingdom)

Purpose:? To determine the prevalence of myelinated retinal nerve fibers in the adult Indian population. Methods:? The Central India Eye and Medical Study performed in rural Central India included 4711 participants aged 30+ years. The participants underwent a detailed ophthalmic and medical examination. Results:? Readable fundus photographs were available for 8645 eyes of 4485 (95.2%) subjects. Myelinated retinal nerve fibers were detected in 52 eyes (46 subjects) with a prevalence rate of 0.58?±?0.08 per 100 eyes [95% confidence interval (CI): 0.42, 0.74] and 1.03?±?0.15 per 100 subjects (95%CI: 0.73, 1.32). Prevalence of myelinated retinal nerve fibers was significantly associated hyperopic refractive error (p?=?0.008; OR: 1.31; 95%CI: 1.07, 1.59). It was not significantly associated with age (p?=?0.11), best corrected visual acuity (logMAR; p?=?0.33), intraocular pressure (p?=?0.09), amount of nuclear cataract (p?=?0.93), optic disc area (p?=?0.60), presence of glaucomatous optic nerve atrophy (p?=?0.62), and early age-related macular degeneration (p?=?0.53). Conclusions:? Myelinated retinal nerve fibers are present in about 10 out of 1000 adult Indians in rural Central India, with a higher prevalence in hyperopic eyes. Prevalence of myelinated retinal nerve fibers was not associated with age, visual acuity, glaucoma and macular degeneration.

Nangia V; Jonas JB; Khare A; Bhate K; Agarwal S; Panda-Jonas S

2013-07-01

276

Myelin contributes to the parallel orientation of axonal growth on white matter in vitro  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Brain and spinal cord white matter can support extensive axonal growth. This growth is generally constrained to an orientation that is parallel to the longitudinal axis of the fiber tract. This constraint is presumably due to permissive and non-permissive substrates that are interleaved with each other and oriented in parallel within the tract. Results Embryonic chick sympathetic neurons were cultured on cryostat sections of rat brain and the orientation of neurite growth on white matter was assessed. To determine if haptotaxis is sufficient to guide parallel neurite growth, neurons were cultured under conditions designed to interfere with interactions between growing neurites and factors that act as biochemical contact guidance cues but not interactions with haptotactic cues. Under these conditions, neurites extending on white matter were not exclusively oriented in parallel to the fiber tract, suggesting that biochemical cues are involved. To assess the role of myelin in guiding parallel neurite growth, neurons were cultured on myelin-deficient corpus callosum. These neurons also extended neurites that were not constrained to a parallel orientation. Moreover, preincubation with NGF and treatment with cAMP analogs, manipulations that attenuate overall myelin-mediated inhibition of neurite growth, also led to a reduced parallel orientation of neurite growth. Conclusions The present studies suggest that some of the relevant factors that constrain axonal growth on white matter are not haptotactic in nature and appear to be partly mediated by factors that are associated with myelin and may involve myelin-associated "inhibitors".

Pettigrew David B; Crutcher Keith A

2001-01-01

277

Erythropoietin (EPO) Increases Myelin Gene Expression in CG4 Oligodendrocyte Cells through the Classical EPO Receptor.  

UK PubMed Central (United Kingdom)

Erythropoietin (EPO) has protective effects in neurodegenerative and neuroinflammatory diseases, including in animal models of multiple sclerosis, where EPO decreases disease severity. EPO also promotes neurogenesis and is protective in models of toxic demyelination. In this study, we asked whether EPO could promote neurorepair by also inducing remyelination. In addition, we investigated whether the effect of EPO could be mediated by the classical erythropoietic EPO receptor (EPOR), since it is still questioned if EPOR is functional in nonhematopoietic cells. Using CG4 cells, a line of rat oligodendrocyte precursor cells, we found that EPO increases the expression of myelin genes (myelin oligodendrocyte glycoprotein [MOG] and myelin basic protein [MBP]). EPO had no effect in wild-type CG4 cells, which do not express EPOR, whereas it increased MOG and MBP expression in cells engineered to overexpress EPOR (CG4-EPOR). This was reflected in a marked increase in MOG protein levels, as detected by Western blot. In these cells, EPO induced by 10-fold the early growth response gene 2 (Egr2), which is required for peripheral myelination. However, Egr2 silencing with a siRNA did not reverse the effect of EPO, indicating that EPO acts through other pathways. In conclusion, EPO induces the expression of myelin genes in oligodendrocytes and this effect requires the presence of EPOR. This study demonstrates that EPOR can mediate neuroreparative effects.

Cervellini I; Annenkov A; Brenton T; Chernajovsky Y; Ghezzi P; Mengozzi M

2013-01-01

278

Erythropoietin (EPO) Increases Myelin Gene Expression in CG4 Oligodendrocyte Cells through the Classical EPO Receptor.  

Science.gov (United States)

Erythropoietin (EPO) has protective effects in neurodegenerative and neuroinflammatory diseases, including in animal models of multiple sclerosis, where EPO decreases disease severity. EPO also promotes neurogenesis and is protective in models of toxic demyelination. In this study, we asked whether EPO could promote neurorepair by also inducing remyelination. In addition, we investigated whether the effect of EPO could be mediated by the classical erythropoietic EPO receptor (EPOR), since it is still questioned if EPOR is functional in nonhematopoietic cells. Using CG4 cells, a line of rat oligodendrocyte precursor cells, we found that EPO increases the expression of myelin genes (myelin oligodendrocyte glycoprotein [MOG] and myelin basic protein [MBP]). EPO had no effect in wild-type CG4 cells, which do not express EPOR, whereas it increased MOG and MBP expression in cells engineered to overexpress EPOR (CG4-EPOR). This was reflected in a marked increase in MOG protein levels, as detected by Western blot. In these cells, EPO induced by 10-fold the early growth response gene 2 (Egr2), which is required for peripheral myelination. However, Egr2 silencing with a siRNA did not reverse the effect of EPO, indicating that EPO acts through other pathways. In conclusion, EPO induces the expression of myelin genes in oligodendrocytes and this effect requires the presence of EPOR. This study demonstrates that EPOR can mediate neuroreparative effects. PMID:23821361

Cervellini, Ilaria; Annenkov, Alexander; Brenton, Thomas; Chernajovsky, Yuti; Ghezzi, Pietro; Mengozzi, Manuela

2013-08-28

279

miR-23 regulation of lamin B1 is crucial for oligodendrocyte development and myelination.  

UK PubMed Central (United Kingdom)

Duplication of the gene encoding lamin B1 (LMNB1) with increased mRNA and protein levels has been shown to cause severe myelin loss in the brains of adult-onset autosomal dominant leukodystrophy patients. Similar to many neurodegenerative disorders, patients with adult-onset autosomal dominant leukodystrophy are phenotypically normal until adulthood and the defect is specific to the central nervous system despite the ubiquitous expression pattern of lamin B1. We set out to dissect the molecular mechanisms underlying this demyelinating phenotype. Increased lamin B1 expression results in disturbances of inner nuclear membrane proteins, chromatin organization and nuclear pore transport in vitro. It also leads to premature arrest of oligodendrocyte differentiation, which might be caused by reduced transcription of myelin genes and by mislocalization of myelin proteins. We identified the microRNA miR-23 as a negative regulator of lamin B1 that can ameliorate the consequences of excessive lamin B1 at the cellular level. Our results indicate that regulation of lamin B1 is important for myelin maintenance and that miR-23 contributes to this process, at least in part, by downregulating lamin B1, therefore establishing novel functions of lamin B1 and miR-23 in the regulation of oligodendroglia development and myelin formation in vitro.

Lin ST; Fu YH

2009-03-01

280

miR-23 regulation of lamin B1 is crucial for oligodendrocyte development and myelination.  

Science.gov (United States)

Duplication of the gene encoding lamin B1 (LMNB1) with increased mRNA and protein levels has been shown to cause severe myelin loss in the brains of adult-onset autosomal dominant leukodystrophy patients. Similar to many neurodegenerative disorders, patients with adult-onset autosomal dominant leukodystrophy are phenotypically normal until adulthood and the defect is specific to the central nervous system despite the ubiquitous expression pattern of lamin B1. We set out to dissect the molecular mechanisms underlying this demyelinating phenotype. Increased lamin B1 expression results in disturbances of inner nuclear membrane proteins, chromatin organization and nuclear pore transport in vitro. It also leads to premature arrest of oligodendrocyte differentiation, which might be caused by reduced transcription of myelin genes and by mislocalization of myelin proteins. We identified the microRNA miR-23 as a negative regulator of lamin B1 that can ameliorate the consequences of excessive lamin B1 at the cellular level. Our results indicate that regulation of lamin B1 is important for myelin maintenance and that miR-23 contributes to this process, at least in part, by downregulating lamin B1, therefore establishing novel functions of lamin B1 and miR-23 in the regulation of oligodendroglia development and myelin formation in vitro. PMID:19259393

Lin, Shu-Ting; Fu, Ying-Hui

2009-02-02

 
 
 
 
281

Myelin gangliosides in developing rats: the influence of maternal ethanol consumption.  

UK PubMed Central (United Kingdom)

The present study examined myelin gangliosides in the developing offspring of rats that were pair-fed control or ethanol liquid diets prior to and during gestation. Between 17 and 31 days of age, we observed an increase in the proportion of GM1 in myelin (from 15% to 38% of ganglioside sialic acid) and a decrease in the proportion of GT1b (from 26% to 4%). GM4 was detected at all ages examined. Between 17 and 31 days of age, there was an increase in the proportion of N-acetylmannosamine-derived radioactivity associated with GM1 (from 16% to 22%) and GM4 (from 5% to 13%), and a decrease in that associated with GT1b (from 24% to 4%). Small, but significant (p less than 0.05), developmentally related differences were found in GD2 and GD3. Detection of GM4 in myelin of young rats in the present study appears to depend on the use of nonpartitioning methods of ganglioside extraction. Although the distribution of myelin gangliosides and radioactivity was near-normal in ethanol-treated pups, there was a consistent decrease in the proportion and radioactivity associated with the major myelin ganglioside, GM1.

Gnaedinger JM; Noronha AB; Druse MJ

1984-05-01

282

Erythropoietin (EPO) Increases Myelin Gene Expression in CG4 Oligodendrocyte Cells through the Classical EPO Receptor  

Science.gov (United States)

Erythropoietin (EPO) has protective effects in neurodegenerative and neuroinflammatory diseases, including in animal models of multiple sclerosis, where EPO decreases disease severity. EPO also promotes neurogenesis and is protective in models of toxic demyelination. In this study, we asked whether EPO could promote neurorepair by also inducing remyelination. In addition, we investigated whether the effect of EPO could be mediated by the classical erythropoietic EPO receptor (EPOR), since it is still questioned if EPOR is functional in nonhematopoietic cells. Using CG4 cells, a line of rat oligodendrocyte precursor cells, we found that EPO increases the expression of myelin genes (myelin oligodendrocyte glycoprotein [MOG] and myelin basic protein [MBP]). EPO had no effect in wild-type CG4 cells, which do not express EPOR, whereas it increased MOG and MBP expression in cells engineered to overexpress EPOR (CG4-EPOR). This was reflected in a marked increase in MOG protein levels, as detected by Western blot. In these cells, EPO induced by 10-fold the early growth response gene 2 (Egr2), which is required for peripheral myelination. However, Egr2 silencing with a siRNA did not reverse the effect of EPO, indicating that EPO acts through other pathways. In conclusion, EPO induces the expression of myelin genes in oligodendrocytes and this effect requires the presence of EPOR. This study demonstrates that EPOR can mediate neuroreparative effects.

Cervellini, Ilaria; Annenkov, Alexander; Brenton, Thomas; Chernajovsky, Yuti; Ghezzi, Pietro; Mengozzi, Manuela

2013-01-01

283

Antibodies to myelin P0 and ceramide perpetuate neuropathy in long standing treated leprosy patients.  

UK PubMed Central (United Kingdom)

Anti neural antibodies are known to play a role in the immunopathogenesis of nerve damage in leprosy and HIV/AIDS. Myelin Protein zero (P0) and ceramide are two nerve components which maintain the integrity of the peripheral nerve. The present study was undertaken to identify antibodies to myelin P0 and ceramide in the sera of treated leprosy patients, HIV positive individuals and healthy subjects using enzyme linked immunosorbant assay (ELISA). The results revealed that treated leprosy patients continue to have significantly elevated myelin P0 and ceramide antibody levels as compared to healthy subjects (P < 0.05). The elevated antibody response to myelin P0 and ceramide in leprosy patients indicate a low grade autoimmune activity that perpetuates nerve damage in treated leprosy. There was no significant difference in the myelin P0 and ceramide antibody levels between HIV positive and healthy subjects (P > 0.05) suggesting that these antibodies do not play a role in early HIV infection.

Raju R; Devi SK; Mehervani C; Kumar AS; Meena AK; Reddy PP; Pranay P; Jain S; Archelos-Gracia JJ; Suneetha S; Suneetha LM

2011-05-01

284

Electrophoretic separation of purified myelin: a method to improve the protein pattern resolving.  

UK PubMed Central (United Kingdom)

Myelin sheath is a lipid-rich membrane, consisting of 70% lipid and 30% proteins, that is involved in physiological and pathological processes. For this reason its protein composition has been often investigated, principally by two-dimensional electrophoresis; however, the consistent lipid content makes it difficult to obtain good proteins separation. To improve the resolution of myelin proteins in a denaturing monodimensional gel electrophoresis, we examined several mixtures for the denaturation of the sample, utilizing different detergents and reducing agents. The definition of the protein pattern was analyzed by both "Blue Silver" Coomassie staining and Western Blot analysis against myelin basic protein, one of the most represented myelin proteins. The best resolution is observed when the sample was incubated with a mixture containing 1.25% dithiothreitol, 4 M urea, and 1% dodecyl maltoside or 1 % 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate, prior to addition of denaturing agents. In conclusion, this work describes a novel method to improve the separation of myelin proteins in a monodimensional gel electrophoresis. It may be also useful for investigating other lipid-rich samples.

Ravera S; Bartolucci M; Barbarito G; Calzia D; Panfoli I

2013-01-01

285

Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan's disease.  

Science.gov (United States)

Canavan's disease (CD) is a fatal, hereditary disorder of CNS development that has been linked to mutations in the gene for the enzyme aspartoacylase (ASPA) (EC 3.5.1.15). ASPA acts to hydrolyze N-acetylaspartate (NAA) into l-aspartate and acetate, but the connection between ASPA deficiency and the failure of proper CNS development is unclear. We hypothesize that one function of ASPA is to provide acetate for the increased lipid synthesis that occurs during postnatal CNS myelination. The gene encoding ASPA has been inactivated in the mouse model of CD, and here we show significant decreases in the synthesis of six classes of myelin-associated lipids, as well as reduced acetate levels, in the brains of these mice at the time of peak postnatal CNS myelination. Analysis of the lipid content of white matter from a human CD patient showed decreased cerebroside and sulfatide relative to normal white matter. These results demonstrate that myelin lipid synthesis is significantly compromised in CD and provide direct evidence that defective myelin synthesis, resulting from a deficiency of NAA-derived acetate, is involved in the pathogenesis of CD. PMID:15784740

Madhavarao, Chikkathur N; Arun, Peethambaran; Moffett, John R; Szucs, Sylvia; Surendran, Sankar; Matalon, Reuben; Garbern, James; Hristova, Diana; Johnson, Anne; Jiang, Wei; Namboodiri, M A Aryan

2005-03-22

286

Cthrc1 is a negative regulator of myelination in Schwann cells.  

UK PubMed Central (United Kingdom)

The analysis of the molecular mechanisms involved in the initial interaction between neurons and Schwann cells is a key issue in understanding the myelination process. We recently identified Cthrc1 (Collagen triple helix repeat containing 1) as a gene upregulated in Schwann cells upon interaction with the axon. Cthrc1 encodes a secreted protein previously shown to be involved in migration and proliferation in different cell types. We performed a functional analysis of Cthrc1 in Schwann cells by loss-of- and gain-of-function approaches using RNA interference knockdown in cell culture and a transgenic mouse line that overexpresses the gene. This work establishes that Cthrc1 enhances Schwann cell proliferation but prevents myelination. In particular, time-course analysis of myelin formation intransgenic animals reveals that overexpression of Cthrc1 in Schwann cells leads to a delay in myelin formation with cells maintaining a proliferative state. Our data, therefore, demonstrate that Cthrc1 plays a negative regulatory role, fine-tuning the onset of peripheral myelination.

Apra C; Richard L; Coulpier F; Blugeon C; Gilardi-Hebenstreit P; Vallat JM; Lindner V; Charnay P; Decker L

2012-03-01

287

Lck tyrosine kinase mediates ?1-integrin signalling to regulate Schwann cell migration and myelination.  

UK PubMed Central (United Kingdom)

The interaction between laminin and ?1-integrin on the surface of Schwann cells regulates Schwann cell proliferation, maturation and differentiation. However, the signalling mediators that fine-tune these outcomes are not fully elucidated. Here we show that lymphoid cell kinase is the crucial effector of ?1-integrin signalling in Schwann cells. Lymphoid cell kinase is activated after laminin treatment of Schwann cells, while downregulation of ?1-integrin with short interfering RNAs inhibits lymphoid cell kinase phosphorylation. Treatment of Schwann cells with a selective lymphoid cell kinase inhibitor reveals a pathway that involves paxillin and CrkII, which ultimately elevates Rac-GTP levels to induce radial lamellipodia formation. Inhibition of lymphoid cell kinase in Schwann cell-dorsal root ganglion cocultures and dorsal root ganglions from Lck(-/-) mice show a reduction of Schwann cell longitudinal migration, reduced myelin formation and internode length. Finally, Lck(-/-) mice exhibit delays in myelination, thinner myelin with abnormal g-ratios and aberrant myelin outfoldings. Our data implicate lymphoid cell kinase as a major regulator of cytoskeletal dynamics, migration and myelination in the peripheral nervous system.

Ness JK; Snyder KM; Tapinos N

2013-01-01

288

Lck tyrosine kinase mediates ?1-integrin signalling to regulate Schwann cell migration and myelination  

Science.gov (United States)

The interaction between laminin and ?1-integrin on the surface of Schwann cells regulates Schwann cell proliferation, maturation and differentiation. However, the signalling mediators that fine-tune these outcomes are not fully elucidated. Here we show that lymphoid cell kinase is the crucial effector of ?1-integrin signalling in Schwann cells. Lymphoid cell kinase is activated after laminin treatment of Schwann cells, while downregulation of ?1-integrin with short interfering RNAs inhibits lymphoid cell kinase phosphorylation. Treatment of Schwann cells with a selective lymphoid cell kinase inhibitor reveals a pathway that involves paxillin and CrkII, which ultimately elevates Rac-GTP levels to induce radial lamellipodia formation. Inhibition of lymphoid cell kinase in Schwann cell-dorsal root ganglion cocultures and dorsal root ganglions from Lck?/? mice show a reduction of Schwann cell longitudinal migration, reduced myelin formation and internode length. Finally, Lck?/? mice exhibit delays in myelination, thinner myelin with abnormal g-ratios and aberrant myelin outfoldings. Our data implicate lymphoid cell kinase as a major regulator of cytoskeletal dynamics, migration and myelination in the peripheral nervous system.

Ness, Jennifer K.; Snyder, Kristin M.; Tapinos, Nikos

2013-01-01

289

Dynamic changes in myelin aberrations and oligodendrocyte generation in chronic amyloidosis in mice and men.  

Science.gov (United States)

Myelin loss is frequently observed in human Alzheimer's disease (AD) and may constitute to AD-related cognitive decline. A potential source to repair myelin defects are the oligodendrocyte progenitor cells (OPCs) present in an adult brain. However, until now, little is known about the reaction of these cells toward amyloid plaque deposition neither in human AD patients nor in the appropriate mouse models. Therefore, we analyzed cells of the oligodendrocyte lineage in a mouse model with chronic plaque deposition (APPPS1 mice) and samples from human patients. In APPPS1 mice defects in myelin integrity and myelin amount were prevalent at 6 months of age but normalized to control levels in 9-month-old mice. Concomitantly, we observed an increase in the proliferation and differentiation of OPCs in the APPPS1 mice at this specific time window (6-8 months) implying that improvements in myelin aberrations may result from repair mechanisms mediated by OPCs. However, while we observed a higher number of cells of the oligodendrocyte lineage (Olig2+ cells) in APPPS1 mice, OLIG2+ cells were decreased in number in postmortem human AD cortex. Our data demonstrate that oligodendrocyte progenitors specifically react to amyloid plaque deposition in an AD-related mouse model as well as in human AD pathology, although with distinct outcomes. Strikingly, possible repair mechanisms from newly generated oligodendrocytes are evident in APPPS1 mice, whereas a similar reaction of oligodendrocyte progenitors seems to be strongly limited in final stages of human AD pathology. PMID:23090919

Behrendt, Gwendolyn; Baer, Kristin; Buffo, Annalisa; Curtis, Maurice A; Faull, Richard L; Rees, Mark I; Götz, Magdalena; Dimou, Leda

2012-10-22

290

Dynamic changes in myelin aberrations and oligodendrocyte generation in chronic amyloidosis in mice and men.  

UK PubMed Central (United Kingdom)

Myelin loss is frequently observed in human Alzheimer's disease (AD) and may constitute to AD-related cognitive decline. A potential source to repair myelin defects are the oligodendrocyte progenitor cells (OPCs) present in an adult brain. However, until now, little is known about the reaction of these cells toward amyloid plaque deposition neither in human AD patients nor in the appropriate mouse models. Therefore, we analyzed cells of the oligodendrocyte lineage in a mouse model with chronic plaque deposition (APPPS1 mice) and samples from human patients. In APPPS1 mice defects in myelin integrity and myelin amount were prevalent at 6 months of age but normalized to control levels in 9-month-old mice. Concomitantly, we observed an increase in the proliferation and differentiation of OPCs in the APPPS1 mice at this specific time window (6-8 months) implying that improvements in myelin aberrations may result from repair mechanisms mediated by OPCs. However, while we observed a higher number of cells of the oligodendrocyte lineage (Olig2+ cells) in APPPS1 mice, OLIG2+ cells were decreased in number in postmortem human AD cortex. Our data demonstrate that oligodendrocyte progenitors specifically react to amyloid plaque deposition in an AD-related mouse model as well as in human AD pathology, although with distinct outcomes. Strikingly, possible repair mechanisms from newly generated oligodendrocytes are evident in APPPS1 mice, whereas a similar reaction of oligodendrocyte progenitors seems to be strongly limited in final stages of human AD pathology.

Behrendt G; Baer K; Buffo A; Curtis MA; Faull RL; Rees MI; Götz M; Dimou L

2013-02-01

291

Split mesencephalon: diplomyelia of the basicranium.  

UK PubMed Central (United Kingdom)

We report a novel case of congenitally split mesencephalon, in a 3-year old with hydrocephalus. We speculate that the ontogenetic mechanism is shared with split cord malformations (SCM). Our case adds to the two other cases of basicranial SCM which involved more caudal brainstem.

Jayasekera BA; Pereira EA; Magdum S

2013-08-01

292

Locally Unknotted Spines of Heegaard Splittings  

CERN Multimedia

We show that under reasonable conditions, the spines of the handlebodies of a strongly reducible Heegaard splitting will intersect a closed ball in a graph which is isotopic into the boundary of the ball. This is in some sense a generalization of the results by Scharlemann on how a strongly irreducible Heegaard splitting surface can intersect a ball.

Johnson, J

2004-01-01

293

Evaluation of Weight Uniformity of Splitted Tablet  

Directory of Open Access Journals (Sweden)

Full Text Available Tablet-splitting is a widespread practice among all sectors of health care for different reasons: it increases dose flexibility, makes tablet parts easier to swallow and allows cost savings for both patients and healthcare providers. However, the tablet parts obtained are often not equal in size, and a substantial amount of tablet can be lost during splitting. This paper is a report of a study conducted to quantify the mean deviation from theoretical weight and the mean weight loss, of three different tablet preparations commonly used to manage hypertension. The tablets were Verapamil Hydrochloride 80mg, Metoprolol Tartrate 50mg and Atenolol 50mg. A volunteer was used in the study to split 30 randomly selected tablet of each of the preparation using two different routine methods; manual splitting and with a kitchen knife. Before and after splitting, tablets and tablet parts were weighed using an analytical balance. All the methods showed significant deviation of weight than the theoretical. Large dose deviations or weight losses can occur while splitting tablets which could have serious clinical consequences for medications with a narrow therapeutic-toxic range. On the basis of the results in this report, we recommend use of a splitting device when splitting cannot be avoided.

Md. Hassan Kawsar; Md. Zia Uddin; Aninda Kumar Nath; Mycal Dutta

2010-01-01

294

Quasiperiodic Tip Splitting in Directional Solidification  

CERN Document Server

We report experimental results on the tip splitting dynamics of seaweed growth in directional solidification of succinonitrile alloys with poly(ethylene oxide) or acetone as solutes. The seaweed or dense branching morphology was selected by solidifying grains which are oriented close to the {111} plane. Despite the random appearance of the growth, a quasiperiodic tip splitting morphology was observed in which the tip alternately splits to the left and to the right. The tip splitting frequency f was found to be related to the growth velocity V as a power law f V^{1.5}. This finding is consistent with the predictions of a tip splitting model that is also presented. Small anisotropies are shown to lead to different kinds of seaweed morphologies.

Utter, B C; Bodenschatz, E

2001-01-01

295

Interplay between LXR and Wnt/?-catenin signaling in the negative regulation of peripheral myelin genes by oxysterols.  

UK PubMed Central (United Kingdom)

Oxysterols are reactive molecules generated from the oxidation of cholesterol. Their implication in cholesterol homeostasis and in the progression of neurodegenerative disorders is well known, but few data are available for their functions in the peripheral nervous system. Our aim was to study the influence of oxysterols on myelin gene expression and myelin sheath formation in peripheral nerves. We show by gas chromatography/mass spectrometry that Schwann cells and sciatic nerves contain 24(S)-hydroxycholesterol, 25-hydroxycholesterol, and 27-hydroxycholesterol and that they express their biosynthetic enzymes and receptors (liver X receptors LXR? and LXR?). We demonstrate that oxysterols inhibit peripheral myelin gene expression [myelin protein zero (MPZ) and peripheral myelin protein-22 (PMP22)] in a Schwann cell line. This downregulation is mediated by either LXR? or LXR?, depending on the promoter context, as suggested by siRNA strategy and chromatin immunoprecipitation assays in Schwann cells and in the sciatic nerve of LXR knock-out mice. Importantly, the knock-out of LXR in mice results in thinner myelin sheaths surrounding the axons. Oxysterols repress myelin genes via two mechanisms: by binding of LXRs to myelin gene promoters and by inhibiting the Wnt/?-catenin pathway that is crucial for the expression of myelin genes. The Wnt signaling components (Disheveled, TCF/LEF, ?-catenin) are strongly repressed by oxysterols. Furthermore, the recruitment of ?-catenin at the levels of the MPZ and PMP22 promoters is decreased. Our data reveal new endogenous mechanisms for the negative regulation of myelin gene expression, highlight the importance of oxysterols and LXR in peripheral nerve myelination, and open new perspectives of treating demyelinating diseases with LXR agonists.

Makoukji J; Shackleford G; Meffre D; Grenier J; Liere P; Lobaccaro JM; Schumacher M; Massaad C

2011-06-01

296

Split structures in general relativity  

Energy Technology Data Exchange (ETDEWEB)

General approach to decomposition of the tangent bundle of pseudo-Riemannian manifolds, and the associated decomposition of geometric objects are constructed on the basis of the invariantly defined split structure. We define the main geometric objects characterizing decomposition. Invariant non-holonomic generalizations of the Gauss-Codazzi-Ricci`s relations have been obtained. All the known types of decompositions (used in theory of frames of reference for the general relativity, in the Hamiltonian formulation for gravity, in the Cauchy problem, in the theory of stationary spaces, and so on) follow from the present work as special cases when fixing the basis and dimensions of subbundles, and parametrization of a basis of decomposition. Method of decomposition have been applied here for the relativistic configurations of a perfect fluid. Discussing an invariant form of the equations of motion we have found the invariant equilibrium conditions and their (3+1) decomposed form. The invariant formulation of the conservation law for the curl have been obtained. (author)

Gladush, V. [Department of Physics, Dnepropetrovsk State University, Dnepropetrovsk (Ukraine)

1999-01-01

297

Split supersymmetry in unified models  

Energy Technology Data Exchange (ETDEWEB)

In the context of split supersymmetry, the gaugino mass spectrum seems to be very important to satisfy the dark matter content of the universe and the gauge coupling unification. In this Letter, we have considered various sources of gaugino masses in the context of unified models. We show that the gaugino mass spectrum varies in different unification pictures. In the context of SU(5), we have found that the bino/wino mass ratio can be close to one at the weak scale which is helpful to satisfy the WMAP data. The gluino/wino mass ratio is also different from the usual scenario of unified gaugino masses. The gaugino masses can be around one TeV and m{sub SUSY} is chosen so that the gluino mass does not create any cosmological problem. In the context of the Pati-Salam model, we show that the gluino mass can be made very heavy even after maintaining the unification of the gauge couplings.

Dutta, Bhaskar [Department of Physics, University of Regina, Regina, Saskatchewan, S4S 0A2 (Canada)]. E-mail: duttabh@yogi.phys.uregina.ca; Mimura, Yukihiro [Department of Physics, University of Regina, Regina, Saskatchewan, S4S 0A2 (Canada)

2005-10-27

298

Split supersymmetry in unified models  

International Nuclear Information System (INIS)

In the context of split supersymmetry, the gaugino mass spectrum seems to be very important to satisfy the dark matter content of the universe and the gauge coupling unification. In this Letter, we have considered various sources of gaugino masses in the context of unified models. We show that the gaugino mass spectrum varies in different unification pictures. In the context of SU(5), we have found that the bino/wino mass ratio can be close to one at the weak scale which is helpful to satisfy the WMAP data. The gluino/wino mass ratio is also different from the usual scenario of unified gaugino masses. The gaugino masses can be around one TeV and mSUSY is chosen so that the gluino mass does not create any cosmological problem. In the context of the Pati-Salam model, we show that the gluino mass can be made very heavy even after maintaining the unification of the gauge couplings.

2005-10-27

299

Innovative solar thermochemical water splitting.  

Energy Technology Data Exchange (ETDEWEB)

Sandia National Laboratories (SNL) is evaluating the potential of an innovative approach for splitting water into hydrogen and oxygen using two-step thermochemical cycles. Thermochemical cycles are heat engines that utilize high-temperature heat to produce chemical work. Like their mechanical work-producing counterparts, their efficiency depends on operating temperature and on the irreversibility of their internal processes. With this in mind, we have invented innovative design concepts for two-step solar-driven thermochemical heat engines based on iron oxide and iron oxide mixed with other metal oxides (ferrites). The design concepts utilize two sets of moving beds of ferrite reactant material in close proximity and moving in opposite directions to overcome a major impediment to achieving high efficiency--thermal recuperation between solids in efficient counter-current arrangements. They also provide inherent separation of the product hydrogen and oxygen and are an excellent match with high-concentration solar flux. However, they also impose unique requirements on the ferrite reactants and materials of construction as well as an understanding of the chemical and cycle thermodynamics. In this report the Counter-Rotating-Ring Receiver/Reactor/Recuperator (CR5) solar thermochemical heat engine and its basic operating principals are described. Preliminary thermal efficiency estimates are presented and discussed. Our ferrite reactant material development activities, thermodynamic studies, test results, and prototype hardware development are also presented.

Hogan, Roy E. Jr.; Siegel, Nathan P.; Evans, Lindsey R.; Moss, Timothy A.; Stuecker, John Nicholas (Robocasting Enterprises, Albuquerque, NM); Diver, Richard B., Jr.; Miller, James Edward; Allendorf, Mark D. (Sandia National Laboratories, Livermore, CA); James, Darryl L. (Texas Tech University, Lubbock, TX)

2008-02-01

300

Autophagy promotes oligodendrocyte survival and function following dysmyelination in a long-lived myelin mutant.  

UK PubMed Central (United Kingdom)

The Long-Evans shaker (les) rat has a mutation in myelin basic protein that results in severe CNS dysmyelination and subsequent demyelination during development. During this time, les oligodendrocytes accumulate cytoplasmic vesicles, including lysosomes and membrane-bound organelles. However, the mechanism and functional relevance behind these oligodendrocyte abnormalities in les have not been investigated. Using high-magnification electron microscopy, we identified the accumulations in les oligodendrocytes as early and late autophagosomes. Additionally, immunohistochemistry and Western blots showed an increase in autophagy markers in les. However, autophagy did not precede the death of les oligodendrocytes. Instead, upregulating autophagy promoted membrane extensions in les oligodendrocytes in vitro. Furthermore, upregulating autophagy in les rats via intermittent fasting increased the proportion of myelinated axons as well as myelin sheath thickness in les and control rats. Overall, this study provides insight into the abnormalities described in les as well as identifying a novel mechanism that promotes the survival and function of oligodendrocytes.

Smith CM; Mayer JA; Duncan ID

2013-05-01

 
 
 
 
301

Structure and expression of a novel compact myelin protein - Small VCP-interacting protein (SVIP).  

Science.gov (United States)

SVIP (small p97/VCP-interacting protein) was initially identified as one of many cofactors regulating the valosin containing protein (VCP), an AAA+ ATPase involved in endoplasmic-reticulum-associated protein degradation (ERAD). Our previous study showed that SVIP is expressed exclusively in the nervous system. In the present study, SVIP and VCP were seen to be co-localized in neuronal cell bodies. Interestingly, we also observed that SVIP co-localizes with myelin basic protein (MBP) in compact myelin, where VCP was absent. Furthermore, using nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopic measurements, we determined that SVIP is an intrinsically disordered protein (IDP). However, upon binding to the surface of membranes containing a net negative charge, the helical content of SVIP increases dramatically. These findings provide structural insight into interactions between SVIP and myelin membranes. PMID:24055875

Wu, Jiawen; Peng, Dungeng; Voehler, Markus; Sanders, Charles R; Li, Jun

2013-09-18

302

Structure and expression of a novel compact myelin protein - Small VCP-interacting protein (SVIP).  

UK PubMed Central (United Kingdom)

SVIP (small p97/VCP-interacting protein) was initially identified as one of many cofactors regulating the valosin containing protein (VCP), an AAA+ ATPase involved in endoplasmic-reticulum-associated protein degradation (ERAD). Our previous study showed that SVIP is expressed exclusively in the nervous system. In the present study, SVIP and VCP were seen to be co-localized in neuronal cell bodies. Interestingly, we also observed that SVIP co-localizes with myelin basic protein (MBP) in compact myelin, where VCP was absent. Furthermore, using nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopic measurements, we determined that SVIP is an intrinsically disordered protein (IDP). However, upon binding to the surface of membranes containing a net negative charge, the helical content of SVIP increases dramatically. These findings provide structural insight into interactions between SVIP and myelin membranes.

Wu J; Peng D; Voehler M; Sanders CR; Li J

2013-10-01

303

Incorporation of fucose and leucine into PNS myelin proteins in nerves undergoing early Wallerian degeneration  

Energy Technology Data Exchange (ETDEWEB)

The simultaneous incorporation of (/sup 3/H)fucose and (1-/sup 14/C)leucine into normal rat sciatic nerve was examined using an in vitro incubation model. A linear rate of protein precursor uptake was found in purified myelin protein over 1/2-6 hr of incubation utilizing a supplemented medium containing amino acids. This model was then used to examine myelin protein synthesis in nerves undergoing degeneration at 1-4 days following a crush injury. Data showed a statistically significant decrease in the ratio of fucose to leucine at 2, 3, and 4 days of degeneration, which was the consequence of a significant increase in leucine uptake. These results, plus substantial protein recovery in axotomized nerves, are indicative of active synthesis of proteins that purify with myelin during early Wallerian degeneration.

Peterson, R.G.; Baughman, S.; Scheidler, D.M.

1981-02-01

304

Incorporation of fucose and leucine into PNS myelin proteins in nerves undergoing early Wallerian degeneration  

International Nuclear Information System (INIS)

[en] The simultaneous incorporation of [3H]fucose and [1-14C]leucine into normal rat sciatic nerve was examined using an in vitro incubation model. A linear rate of protein precursor uptake was found in purified myelin protein over 1/2-6 hr of incubation utilizing a supplemented medium containing amino acids. This model was then used to examine myelin protein synthesis in nerves undergoing degeneration at 1-4 days following a crush injury. Data showed a statistically significant decrease in the ratio of fucose to leucine at 2, 3, and 4 days of degeneration, which was the consequence of a significant increase in leucine uptake. These results, plus substantial protein recovery in axotomized nerves, are indicative of active synthesis of proteins that purify with myelin during early Wallerian degeneration

1981-01-01

305

Antibodies to myelin P0 and ceramide perpetuate neuropathy in long standing treated leprosy patients.  

Science.gov (United States)

Anti neural antibodies are known to play a role in the immunopathogenesis of nerve damage in leprosy and HIV/AIDS. Myelin Protein zero (P0) and ceramide are two nerve components which maintain the integrity of the peripheral nerve. The present study was undertaken to identify antibodies to myelin P0 and ceramide in the sera of treated leprosy patients, HIV positive individuals and healthy subjects using enzyme linked immunosorbant assay (ELISA). The results revealed that treated leprosy patients continue to have significantly elevated myelin P0 and ceramide antibody levels as compared to healthy subjects (P  0.05) suggesting that these antibodies do not play a role in early HIV infection. PMID:21234675

Raju, Renuka; Devi, S Karuna; Mehervani, C; Kumar, A Shiva; Meena, A K; Reddy, P P; Pranay, Penaguluru; Jain, Suman; Archelos-Gracia, J J; Suneetha, Sujai; Suneetha, Lavanya M

2011-01-14

306

Improving myelin/oligodendrocyte-related dysfunction: a new mechanism of antipsychotics in the treatment of schizophrenia?  

UK PubMed Central (United Kingdom)

Schizophrenia is a severe psychiatric disorder with complex clinical manifestations and its aetiological factors remain unclear. During the past decade, the oligodendrocyte-related myelin dysfunction was proposed as a hypothesis for schizophrenia, supported initially by a series of neuroimaging studies and genetic evidence. Recently, the effects of antipsychotics on myelination and oligodendroglial lineage development and their underlying molecular mechanisms were evaluated. Data from those studies suggest that the antipsychotics-resulting improvement in myelin/oligodendrocyte-related dysfunction may contribute, at least in part, to their therapeutic effect on schizophrenia. Importantly, these findings may provide the basis for a new insight into the therapeutic strategy by targeting the oligodendroglia lineage cells against schizophrenia.

Ren Y; Wang H; Xiao L

2013-04-01

307

A rapid and reproducible assay for modeling myelination by oligodendrocytes using engineered nanofibers.  

UK PubMed Central (United Kingdom)

Current methods for studying oligodendrocyte myelination using primary neurons are limited by the time, cost and reproducibility of myelination in vitro. Nanofibers with diameters of >0.4 ?m fabricated from electrospinning of liquid polystyrene are suitable scaffolds for concentric membrane wrapping by oligodendrocytes. With the advent of aligned electrospinning technology, nanofibers can be rapidly fabricated, standardized, and configured into various densities and patterns as desired. Notably, the minimally permissive culture environment of fibers provides investigators with an opportunity to explore the autonomous oligodendrocyte cellular processes underlying differentiation and myelination. The simplicity of the system is conducive to monitoring oligodendrocyte proliferation, migration, differentiation and membrane wrapping in the absence of neuronal signals. Here we describe protocols for the fabrication and preparation of nanofibers aligned on glass coverslips for the study of membrane wrapping by rodent oligodendrocytes. The entire protocol can be completed within 2 weeks.

Lee S; Chong SY; Tuck SJ; Corey JM; Chan JR

2013-04-01

308

[Normal myelination in childhood brains using MRI--a meta analysis  

UK PubMed Central (United Kingdom)

PURPOSE: To establish age limits for the assessment of normal myelination of the brain on T1-weighted (T1w) and T2-weighted (T2w) images. METHOD: Comparison of previous publications (Barkovich et al. 1988, Grodd 1993, Hayakawa et al. 1990, Hittmair et al. 1994, Martin et al. 1988/1990/1991, Nakagawa et al. 1998, Staudt et al. 1993/1994, Stricker et al. 1990). RESULTS: Despite technical and methodological differences, these studies principally agreed on the timing of myelination for most regions of the brain. Thus, a common time-table could be established: At 1 month, myelin is visible on both T1w and T2w in the medulla oblongata, tegmentum pontis, cerebellar peduncles and vermis, quadrigeminal plate, decussation of superior cerebellar peduncles, thalamus, posterior limb of internal capsule, optic radiation, corona radiata. Thereafter, the myelin-typical signal in the different regions of the brain should be present at the following ages (M = months): anterior limb of internal capsule (2 M: T1w; 7 M: T2w), splenium of corpus callosum (4 M: T1w; 6 M: T2w), genu of corpus callosum (6 M: T1w; 8 M: T2w), centrum semiovale (2 M: T1w; 7 M: T2w). Branching of myelin into the gyri of the telencephalon (= arborization) appears at the latest at: occipital lobe (5 M: T1w; 12 M: T2w) and frontal lobe (7 M: T1w; 14 M: T2w). CONCLUSION: These extracted age limits can be used for a more reliable assessment of myelination than the time-tables from a single study.

Staudt M; Krägeloh-Mann I; Grodd W

2000-10-01

309

Normal myelination of the child brain on MRI - a meta-analysis  

International Nuclear Information System (INIS)

Purpose: To establish age limits for the assessment of normal myelination of the brain on T1-weighted (T1w) and T2-weighted (T2w) images. Method: Comparison of previous publications (Barkovich et al. 1988, Grodd 1993, Hayakawa et al. 1990, Hittmair et al. 1994, Martin et al. 1988/1990/1991, Nakagawa et al. 1998, Staudt et al. 1993/1994, Stricker et al. 1990). Results: Despite technical and methodological differences, these studies principally agreed on the timing of myelination for most regions of the brain. Thus, a common timetable could be established: At 1 month, myelin is visible on both T1w and T2w in the medulla oblongata, tegmentum pontis, cerebellar peduncles and vermis, quadrigeminal plate, decussation of superior cerebellar peduncles, thalamus, posterior limb of internal capsule, optic radiation, corona radiata. Thereafter, the myelin-typical signal in the different regions of the brain should be present at the following ages (M=months): Anterior limb of internal capsule (2 M: T1w; 7 M: T2w), splenium of corpus callosum (4 M: T1w; 6 M: T2w), genu of corpus callosum (6 M: T1w; 8 M: T2w), centrum semiovale (2 M: T1w; 7 M: T2w). Branching of myelin into the gyri of the telencephalon (=arborization) appears at the latest at: occipital lobe (5 M: T1w; 12 M: T2w) and frontal lobe (7 M: T1w; 14 M: T2w). Conclusion: These extracted age limits can be used for a more reliable assessment of myelination than the time-tables from a single study. (orig.)

2000-01-01

310

Erythropoietin treatment alleviates ultrastructural myelin changes induced by murine cerebral malaria  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Cerebral malaria (CM) is a severe complication of malaria with considerable mortality. In addition to acute encephalopathy, survivors frequently suffer from neurological sequelae. The pathogenesis is incompletely understood, hampering the development of an effective, adjunctive therapy, which is not available at present. Previously, erythropoietin (EPO) was reported to significantly improve the survival and outcome in a murine CM model. The study objectives were to assess myelin thickness and ultrastructural morphology in the corpus callosum in murine CM and to adress the effects of EPO treatment in this context. Methods The study consisted of two groups of Plasmodium berghei-infected mice and two groups of uninfected controls that were either treated with EPO or placebo (n?=?4 mice/group). In the terminal phase of murine CM the brains were removed and processed for electron microscopy. Myelin sheaths in the corpus callosum were analysed with transmission electron microscopy and stereology. Results The infection caused clinical CM, which was counteracted by EPO. The total number of myelinated axons was identical in the four groups and mice with CM did not have reduced mean thickness of the myelin sheaths. Instead, CM mice had significantly increased numbers of abnormal myelin sheaths, whereas EPO-treated mice were indistinguishable from uninfected mice. Furthermore, mice with CM had frequent and severe axonal injury, pseudopodic endothelial cells, perivascular oedemas and intracerebral haemorrhages. Conclusions EPO treatment reduced clinical signs of CM and reduced cerebral pathology. Murine CM does not reduce the general thickness of myelin sheaths in the corpus callosum.

Hempel Casper; Hyttel Poul; Staalsř Trine; Nyengaard Jens R; Kurtzhals Jřrgen AL

2012-01-01

311

Locomotion, physical development, and brain myelination in rats treated with ionizing radiation in utero  

Energy Technology Data Exchange (ETDEWEB)

Effects of ionizing radiation on the emergence of locomotion skill and some physical development parameters were studied in laboratory rats (Fisher F-344 inbred strain). Rats were treated with 3 different doses of radiation (150 R, 15 R, and 6.8 R) delivered on the 20th day of the prenatal life. Results indicated that relatively moderate (15 R) to high (150 R) doses of radiation have effects on certain locomotion and physical development parameters. Exposure to 150 R affected pivoting, cliff-avoidance, upper jaw tooth eruption, body weight, and organs, such as brain, cerebral cortex, ovary, kidney, heart and spleen weights. Other parameters, such as negative geotaxis, eye opening, and lower jaw tooth eruption appeared to be affected in the 150 R treated animals. Exposure to 15 R affected pivoting and cliff-avoidance parameters. The cerebral cortex weight of the 15 R treated animals was found to be reduced at the age of day 30. Exposure to 6.8 R had no adverse effects on these parameters. Prenatal exposure to 150 R of radiation reduced the cerebral cortex weight by 22.07% at 30 days of age, and 20.15% at 52 days of age which caused a reduction in cerebral cortex myelin content by 20.16, and 22.89% at the ages of day 30 and day 52 respectively. Exposure to 150 R did not affect the myelin content of the cerebellum or the brain stem; or the myelin concentration (mg myelin/g brain tissue weight) of the cerebral cortex, cerebellum, and the brain stem. Exposure to 15 R, and 6.8 R did not affect either the myelin content or the myelin concentration of these brain areas.

Zaman, M.S.

1989-01-01

312

Structural characterization of the human cerebral myelin sheath by small angle x-ray scattering  

Science.gov (United States)

Myelin is a multi-lamellar membrane surrounding neuronal axons and increasing their conduction velocity. When investigated by small-angle x-ray scattering (SAXS), the lamellar quasi-periodical arrangement of the myelin sheath gives rise to distinct peaks, which allow the determination of its molecular organization and the dimensions of its substructures. In this study we report on the myelin sheath structural determination carried out on a set of human brain tissue samples coming from surgical biopsies of two patients: a man around 60 and a woman nearly 90 years old. The samples were extracted either from white or grey cerebral matter and did not undergo any manipulation or chemical-physical treatment, which could possibly have altered their structure, except dipping them into a formalin solution for their conservation. Analysis of the scattered intensity from white matter of intact human cerebral tissue allowed the evaluation not only of the myelin sheath periodicity but also of its electronic charge density profile. In particular, the thicknesses of the cytoplasm and extracellular regions were established, as well as those of the hydrophilic polar heads and hydrophobic tails of the lipid bilayer. SAXS patterns were measured at several locations on each sample in order to establish the statistical variations of the structural parameters within a single sample and among different samples. This work demonstrates that a detailed structural analysis of the myelin sheath can also be carried out in randomly oriented samples of intact human white matter, which is of importance for studying the aetiology and evolution of the central nervous system pathologies inducing myelin degeneration.

DeFelici, M.; Felici, R.; Ferrero, C.; Tartari, A.; Gambaccini, M.; Finet, S.

2008-10-01

313

Myelin loss and oligodendrocyte pathology in white matter tracts following traumatic brain injury in the rat.  

UK PubMed Central (United Kingdom)

Axonal injury is an important contributor to the behavioral deficits observed following traumatic brain injury (TBI). Additionally, loss of myelin and/or oligodendrocytes can negatively influence signal transduction and axon integrity. Apoptotic oligodendrocytes, changes in the oligodendrocyte progenitor cell (OPC) population and loss of myelin were evaluated at 2, 7 and 21 days following TBI. We used the central fluid percussion injury model (n = 18 and three controls) and the lateral fluid percussion injury model (n = 15 and three controls). The external capsule, fimbriae and corpus callosum were analysed. With Luxol Fast Blue and RIP staining, myelin loss was observed in both models, in all evaluated regions and at all post-injury time points, as compared with sham-injured controls (P ? 0.05). Accumulation of ?-amyloid precursor protein was observed in white matter tracts in both models in areas with preserved and reduced myelin staining. White matter microglial/macrophage activation, evaluated by isolectin B4 immunostaining, was marked at the early time points. In contrast, the glial scar, evaluated by glial fibrillary acidic protein staining, showed its highest intensity 21 days post-injury in both models. The number of apoptotic oligodendrocytes, detected by CC1/caspase-3 co-labeling, was increased in both models in all evaluated regions. Finally, the numbers of OPCs, evaluated with the markers Tcf4 and Olig2, were increased from day 2 (Olig2) or day 7 (Tcf4) post-injury (P ? 0.05). Our results indicate that TBI induces oligodendrocyte apoptosis and widespread myelin loss, followed by a concomitant increase in the number of OPCs. Prevention of myelin loss and oligodendrocyte death may represent novel therapeutic targets for TBI.

Flygt J; Djupsjö A; Lenne F; Marklund N

2013-07-01

314

Myelin loss and oligodendrocyte pathology in white matter tracts following traumatic brain injury in the rat.  

Science.gov (United States)

Axonal injury is an important contributor to the behavioral deficits observed following traumatic brain injury (TBI). Additionally, loss of myelin and/or oligodendrocytes can negatively influence signal transduction and axon integrity. Apoptotic oligodendrocytes, changes in the oligodendrocyte progenitor cell (OPC) population and loss of myelin were evaluated at 2, 7 and 21 days following TBI. We used the central fluid percussion injury model (n = 18 and three controls) and the lateral fluid percussion injury model (n = 15 and three controls). The external capsule, fimbriae and corpus callosum were analysed. With Luxol Fast Blue and RIP staining, myelin loss was observed in both models, in all evaluated regions and at all post-injury time points, as compared with sham-injured controls (P ? 0.05). Accumulation of ?-amyloid precursor protein was observed in white matter tracts in both models in areas with preserved and reduced myelin staining. White matter microglial/macrophage activation, evaluated by isolectin B4 immunostaining, was marked at the early time points. In contrast, the glial scar, evaluated by glial fibrillary acidic protein staining, showed its highest intensity 21 days post-injury in both models. The number of apoptotic oligodendrocytes, detected by CC1/caspase-3 co-labeling, was increased in both models in all evaluated regions. Finally, the numbers of OPCs, evaluated with the markers Tcf4 and Olig2, were increased from day 2 (Olig2) or day 7 (Tcf4) post-injury (P ? 0.05). Our results indicate that TBI induces oligodendrocyte apoptosis and widespread myelin loss, followed by a concomitant increase in the number of OPCs. Prevention of myelin loss and oligodendrocyte death may represent novel therapeutic targets for TBI. PMID:23458840

Flygt, J; Djupsjö, A; Lenne, F; Marklund, N

2013-03-05

315

[Structural characteristics of sural nerve myelin from patients with chronic inflammatory demyelinating polyneuropathy: an X-ray diffraction study  

UK PubMed Central (United Kingdom)

INTRODUCTION AND OBJECTIVE: Using the X ray diffraction technique and the mathematical analysis developed by Luzzati and Mateu, we have studied the structure of nerve myelin from patients with chronic inflammatory demyelinating polyneuropathy (CIDP) in order to quantitatively evaluate the changes occurred in the myelin sheath at structural level. PATIENTS AND METHODS: Sural nerves from 4 patients filling the criteria for CIDP were studied and the results compared to those of 4 other sural nerves extracted from patients who died in the Hospital with no symptoms of peripheral nerve diseases. The structural parameters determined by the mathematical analysis were: the repeat distance between the myelin membranes pairs (D) and its mean standard deviation (sigmaD); the mean number of membrane turns per axon ; the fraction of total myelination (alpha myel) in the nerve, the fraction of membrane pairs not packed in a crystallite (alpha loose) and the degree of disorientation (sigmaw) of the myelin membrane pairs with respect to the fiber axis. RESULTS: The alterations found in pathological nerve myelin were: 1) increase in the packing disorder sigmaD and in the fraction of disordered myelin alpha loose; 2) decrease in the percentage of myelination alpha myel and in the mean number of membrane turns around the axons . CONCLUSIONS: Our results indicate that with these techniques it is possible to detect and quantify demyelination produced by CIDP in human peripheral nerves. In consequence it should be possible to use a similar approach to study other types of polyneuropathy.

Vargas Leal V; Cotúa Salazar M; Borges Iturriza J; Vonasek Golcz E; Vargas R; Céspedes-Caravaca G; Mateu-Suay L

2003-04-01

316

Wnt/beta-catenin signaling is an essential and direct driver of myelin gene expression and myelinogenesis.  

UK PubMed Central (United Kingdom)

Wnt/?-catenin signaling plays a major role in the development of the nervous system and contributes to neuronal plasticity. However, its role in myelination remains unclear. Here, we identify the Wnt/?-catenin pathway as an essential driver of myelin gene expression. The selective inhibition of Wnt components by small interfering RNA or dominant-negative forms blocks the expression of myelin protein zero (MPZ) and peripheral myelin protein 22 (PMP22) in mouse Schwann cells and proteolipid protein in mouse oligodendrocytes. Moreover, the activation of Wnt signaling by recombinant Wnt1 ligand increases by threefold the transcription of myelin genes and enhances the binding of ?-catenin to T-cell factor/lymphoid-enhancer factor transcription factors present in the vicinity of the MPZ and PMP22 promoters. Most important, loss-of-function analyses in zebrafish embryos show, in vivo, a key role for Wnt/?-catenin signaling in the expression of myelin genes and in myelin sheath compaction, both in the peripheral and central nervous systems. Inhibition of Wnt/?-catenin signaling resulted in hypomyelination, without affecting Schwann cell and oligodendrocyte generation or axonal integrity. The present findings attribute to Wnt/?-catenin pathway components an essential role in myelin gene expression and myelinogenesis.

Tawk M; Makoukji J; Belle M; Fonte C; Trousson A; Hawkins T; Li H; Ghandour S; Schumacher M; Massaad C

2011-03-01

317

Microcalorimetric studies of the heats of solution of bovine myelin basic protein.  

UK PubMed Central (United Kingdom)

Heats of solution for myelin basic protein have been determined using microcalorimetry. All aqueous systems studied yielded negative heats of solution; in contrast, trifluoroethanol produced a small positive heat of solution, while reaction with dimethyl sulfoxide was strikingly exothermic. The heat of interaction for native myelin basic protein with 8 M urea at pH 4.0, 29 degrees C, was found to be -79 +/- 16 kcal/mol. The significance of these results in terms of the protein's structural organization is discussed.

Randall CS; Zand R

1985-10-01

318

Heat production associated with a propagated impulse in bullfrog myelinated nerve fibers.  

UK PubMed Central (United Kingdom)

By using heat-sensors constructed with thin film of polyvinylidene fluoride, it was found possible to detect the heat generated by myelinated fibers in the bullfrog sciatic nerve in association with a propagated impulse. The quantity of heat generated (about 0.4 microcal/g at 4.5 degrees C) is roughly two orders of magnitude smaller than that observed in nerves containing only non-myelinated nerve fibers. The smallness of the heat observed is attributed to the localization of the heat sources at the nodes of Ranvier. The major portion of the heat generated is re-absorbed by the nerve.

Tasaki I; Byrne PM

1992-01-01

319

Salt splitting using ceramic membranes  

International Nuclear Information System (INIS)

[en] Many radioactive aqueous wastes in the DOE complex have high concentrations of sodium that can negatively affect waste treatment and disposal operations. Sodium can decrease the durability of waste forms such as glass and is the primary contributor to large disposal volumes. Waste treatment processes such as cesium ion exchange, sludge washing, and calcination are made less efficient and more expensive because of the high sodium concentrations. Pacific Northwest National Laboratory (PNNL) and Ceramatec Inc. (Salt Lake City UT) are developing an electrochemical salt splitting process based on inorganic ceramic sodium (Na), super-ionic conductor (NaSICON) membranes that shows promise for mitigating the impact of sodium. In this process, the waste is added to the anode compartment, and an electrical potential is applied to the cell. This drives sodium ions through the membrane, but the membrane rejects most other cations (e.g., Sr+2, Cs+). The charge balance in the anode compartment is maintained by generating H+ from the electrolysis of water. The charge balance in the cathode is maintained by generating OH-, either from the electrolysis of water or from oxygen and water using an oxygen cathode. The normal gaseous products of the electrolysis of water are oxygen at the anode and hydrogen at the cathode. Potentially flammable gas mixtures can be prevented by providing adequate volumes of a sweep gas, using an alternative reductant or destruction of the hydrogen as it is generated. As H+ is generated in the anode compartment, the pH drops. The process may be operated with either an alkaline (pH>12) or an acidic anolyte (pH

1997-01-01

320

Chow motives of generically split varieties  

CERN Document Server

Let G be an anisotropic linear algebraic group which splits by a field extension of a prime degree. Let X be a projective homogeneous G-variety such that G splits over the function field of X. We prove that under certain conditions the Chow motive of X is isomorphic to a direct sum of twisted copies of an indecomposable motive R. This covers all known examples of motivic decompositions of generically split projective homogeneous varieties (Severi-Brauer varieties, Pfister quadrics, maximal orthogonal Grassmannians) as well as provides new ones (exceptional varieties of types E6 and E8).

Petrov, V; Zainoulline, K; Petrov, Victor; Semenov, Nikita; Zainoulline, Kirill

2006-01-01

 
 
 
 
321

2S Hyperfine splitting of muonic hydrogen  

CERN Document Server

Corrections of orders alpha^5, alpha^6 are calculated in the hyperfine splitting of the 2S state in the muonic hydrogen. The nuclear structure effects are taken into account in the one- and two-loop Feynman amplitudes by means of the proton electromagnetic form factors. Total numerical value of the 2S state hyperfine splitting 22.8148 meV in the (\\mu p) can be considered as reliable estimation for the corresponding experiment with the accuracy 10^{-5}. The value of the Sternheim's hyperfine splitting interval [8\\Delta E^{HFS}(2S)-\\Delta E^{HFS}(1S)] is obtained with the accuracy 10^{-6}.

Martynenko, A P

2004-01-01

322

Muonic hydrogen ground state hyperfine splitting  

CERN Multimedia

Corrections of order alpha^5, alpha^6 are calculated in the hyperfine splitting of muonic hydrogen ground state. Nuclear structure effects are taken into account in one- and two-loop Feynman amplitudes by means of the proton electromagnetic form factors. The modification of the hyperfine splitting part of the Breit potential due to electron vacuum polarization is considered. Total numerical value of the 1S state hyperfine splitting 182.725 meV in (mu p) can play the role of proper estimation for the corresponding experiment with the accuracy 30 ppm.

Faustov, R N

2003-01-01

323

SPLIT LEATHER PRODUCT AND MANUFACTURING METHOD THEREFOR  

UK PubMed Central (United Kingdom)

An aspect of the invention is a split leather product provided with a base material comprising split leather, and a skin layer laminated on a surface of the base material. The skin layer comprises a composite body of an entangled nonwoven fabric formed from microfine fibers, and a polymeric elastomer that impregnates the gaps in the entangled nonwoven fabric. The entangled nonwoven fabric in such a split leather product has the effect of increasing physical strength without detracting from a leather-like texture, in the same way as the longitudinally and transversally crisscrossing collagen fibers in the reticular layer. It is thus possible to obtain a split leather product that resembles leather not only in outward appearance but also in the feel derived from wrinkles and the like resulting when the leather is bent.

YONEDA HISAO; KIMURA YOSHIO; WAKIMOTO YOSHIAKI; MIYAUCHI KIYOHIKO

324

Heegaard splittings with large subsurface distances  

CERN Multimedia

We show that sub-surfaces of a Heegaard surface for which the relative Hempel distance of the splitting is sufficiently high have to appear in any Heegaard surface of genus bounded by half that distance.

Johnson, Jesse; Moriah, Yoav

2010-01-01

325

Split rank of triangle and quadrilateral inequalities  

CERN Document Server

A simple relaxation of two rows of a simplex tableau is a mixed integer set consisting of two equations with two free integer variables and non-negative continuous variables. Recently Andersen, Louveaux, Weismantel and Wolsey (2007) and Cornuejols and Margot (2008) showed that the facet-defining inequalities of this set are either split cuts or intersection cuts obtained from lattice-free triangles and quadrilaterals. Through a result by Cook, Kannan and Schrijver (1990), it is known that one particular class of facet-defining triangle inequality does not have a finite split rank. In this paper, we show that all other facet-defining triangle and quadrilateral inequalities have a finite split-rank. The proof is constructive and given a facet-defining triangle or quadrilateral inequality we present an explicit sequence of split inequalities that can be used to generate it.

Dey, Santanu

2009-01-01

326

Ectrodactyly/split hand feet malformation  

Directory of Open Access Journals (Sweden)

Full Text Available Split-hand/split-foot malformation is a rare limb malformation with median clefts of the hands and feet and aplasia/hypoplasia of the phalanges, metacarpals and metatarsals. When present as an isolated anomaly, it is usually inherited as an autosomal dominant form. We report a case of autosomal recessive inheritance and discuss the antenatal diagnosis, genetic counseling and treatment for the malformation.

Jindal Geetanjali; Parmar Veena; Gupta Vipul

2009-01-01

327

Serre's uniformity in the split Cartan case  

CERN Multimedia

We prove that there exists an integer p_0 such that X_split(p)(Q) is made of cusps and CM-points for any prime p>p_0. Equivalently, for any non-CM elliptic curve E over Q and any prime p>p_0 the image of the Galois representation \\rho_{E,p} is not contained in the normalizer of a split Cartan subgroup. This gives a partial answer to an old question of Serre.

Bilu, Yuri

2008-01-01

328

Heegaard Splittings of Boundary Reducible 3-Manifolds  

CERN Multimedia

In this paper, we shall prove that any Heegaard splitting of a $\\partial$-reducible 3-manifold $M$, say $M=W\\cup V$, can be obtained by doing connected sums, boundary connected sums and self-boundary connected sums from Heegaard splittings of $n$ manifolds $M_{1},..., M_{n}$ where $M_{i}$ is either a solid torus or a $\\partial$-irreducible manifold. Furthermore, $W\\cup V$ is stabilized if and only if one of the factors is stabilized.

Ma, J; Ma, Jiming; Qiu, Ruifeng

2004-01-01

329

Normalizing Heegaard-Scharlemann-Thompson Splittings  

CERN Document Server

We define a Heegaard-Scharlemann-Thompson (HST) splitting of a 3-manifold M to be a sequence of pairwise-disjoint, embedded surfaces, {F_i}, such that for each odd value of i, F_i is a Heegaard splitting of the submanifold of M cobounded by F_{i-1} and F_{i+1}. Our main result is the following: Suppose M (\

Bachman, D C

2003-01-01

330

Analysis of dynamic hashing with deferred splitting  

Energy Technology Data Exchange (ETDEWEB)

Dynamic hashing with deferred splitting is a file organization scheme which increases storage utilization, as compared to standard dynamic hashing. In this scheme, splitting of a bucket is deferred if the bucket is full but its brother can accommodate new records. The performance of the scheme is analyzed. In a typical case the expected storage utilization increases from 69 to 76 %. 5 references, 2 figures.

Veklerov, E.

1985-03-01

331

Detection of flux emergence, splitting, merging, and cancellation of network field. I Splitting and Merging  

CERN Document Server

Frequencies of magnetic patch processes on supergranule boundary, namely flux emergence, splitting, merging, and cancellation, are investigated through an automatic detection. We use a set of line of sight magnetograms taken by the Solar Optical Telescope (SOT) on board Hinode satellite. We found 1636 positive patches and 1637 negative patches in the data set, whose time duration is 3.5 hours and field of view is 112" \\times 112". Total numbers of magnetic processes are followed: 493 positive and 482 negative splittings, 536 positive and 535 negative mergings, 86 cancellations, and 3 emergences. Total numbers of emergence and cancellation are significantly smaller than those of splitting and merging. Further, frequency dependences of merging and splitting processes on flux content are investigated. Merging has a weak dependence on flux content only with a power- law index of 0.28. Timescale for splitting is found to be independent of parent flux content before splitting, which corresponds to \\sim 33 minutes. ...

Iida, Y; Yokoyama, T

2012-01-01

332

Effect of membrane splitting on transmembrane polypeptides.  

Science.gov (United States)

We investigated the effect of membrane splitting on the primary structure of human erythrocyte membrane polypeptides. Monolayers of intact, chemically unmodified cells were freeze-fractured and examined by one-dimensional SDS PAGE. Silver-stained gels revealed all major polypeptides that stain with Coomassie Blue as well as all bands that stain with periodic acid Schiff's reagent. Both nonglycosylated and glycosylated membrane polypeptides could be detected at concentrations of only a few nanograms per band. Membrane splitting had no effect on the position or number of bands. Monolayers of intact erythrocytes that had been enzymatically radioiodinated with lactoperoxidase were examined by electrophoresis, fluorography, and liquid scintillation counting. Radioactivity was quantified before and after monolayer formation and splitting, and at several stages of gel staining, drying, and fluorography. Although overexposed fluorographs revealed several minor radioiodinated bands in addition to band 3 and the glycophorins, no new bands were detected in split membrane samples derived from intact cells. These observations support the conclusion that neither the band 3 anion channel nor the glycophorin sialoglycoproteins are fragmented during freeze-fracturing. Although both band 3 and glycophorin partition to the cytoplasmic side of the membrane, preliminary quantitative observations suggest an enrichment of glycophorin in the split extracellular "half" membrane. We conclude that the process of membrane splitting by planar monolayer freeze-fracture does not cleave the covalent polypeptide backbone of any erythrocyte membrane protein, peripheral or integral. PMID:3944190

Fisher, K A; Yanagimoto, K C

1986-02-01

333

Effect of membrane splitting on transmembrane polypeptides.  

UK PubMed Central (United Kingdom)

We investigated the effect of membrane splitting on the primary structure of human erythrocyte membrane polypeptides. Monolayers of intact, chemically unmodified cells were freeze-fractured and examined by one-dimensional SDS PAGE. Silver-stained gels revealed all major polypeptides that stain with Coomassie Blue as well as all bands that stain with periodic acid Schiff's reagent. Both nonglycosylated and glycosylated membrane polypeptides could be detected at concentrations of only a few nanograms per band. Membrane splitting had no effect on the position or number of bands. Monolayers of intact erythrocytes that had been enzymatically radioiodinated with lactoperoxidase were examined by electrophoresis, fluorography, and liquid scintillation counting. Radioactivity was quantified before and after monolayer formation and splitting, and at several stages of gel staining, drying, and fluorography. Although overexposed fluorographs revealed several minor radioiodinated bands in addition to band 3 and the glycophorins, no new bands were detected in split membrane samples derived from intact cells. These observations support the conclusion that neither the band 3 anion channel nor the glycophorin sialoglycoproteins are fragmented during freeze-fracturing. Although both band 3 and glycophorin partition to the cytoplasmic side of the membrane, preliminary quantitative observations suggest an enrichment of glycophorin in the split extracellular "half" membrane. We conclude that the process of membrane splitting by planar monolayer freeze-fracture does not cleave the covalent polypeptide backbone of any erythrocyte membrane protein, peripheral or integral.

Fisher KA; Yanagimoto KC

1986-02-01

334

Myelination process in preterm subjects with periventricular leucomalacia assessed by magnetization transfer ratio  

Energy Technology Data Exchange (ETDEWEB)

Magnetization transfer imaging assesses the myelination status of the brain. To study the progress of myelination in children with periventricular leucomalacia (PVL) by measuring the magnetization transfer ratio (MTR) and to compare the MTR values with normal values. Brain MTR in 28 PVL subjects (16 males, 12 females, gestational age 30.7{+-}2.5 weeks, corrected age 3.1{+-}2.9 years) was measured using a 3D gradient echo sequence (TR/TE 32/8 ms, flip angle 60 , 4 mm/2 mm overlapping sections) without and with magnetization transfer prepulse and compared with normal values for preterm subjects. MTR of white-matter structures followed a monoexponential function model (y=A-B*exp(-x/C)) while the thalamus and caudate nucleus had a poor goodness of fit. MTR of the splenium of the corpus callosum reached a final value lower than normal (0.67 versus 0.70) at a younger age [t(99%) at 10.32 versus 18.90 months; P<0.05]. MTR of the normal-appearing occipital white matter and of the genu of the corpus callosum reached a normal final MTR but at a younger age than normal preterm infants [t(99%) at 8.51 versus 14.50 months and 12.51 versus 20.85 months, respectively]. In PVL subjects, myelination of the splenium is characterized by early arrest and deficient maturation. Accelerated myelination in unaffected white matter might suggest a compensatory process of reorganization. (orig.)

Xydis, Vassilios; Astrakas, Loukas; Gassias, Dimitrios; Argyropoulou, Maria [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); Drougia, Aikaterini; Andronikou, Styliani [University of Ioannina, Neonatology Clinic, Child Health Department, Medical School, Ioannina (Greece)

2006-09-15

335

The Permeability of the Sodium Channel to Organic Cations in Myelinated Nerve  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The relative permeability of sodium channels to 21 organic cations was studied in myelinated nerve fibers. Ionic currents under voltage-clamp conditions were measured in sodium-free solutions containing the test cation. The measured reversal potential and the Goldman equation were used to calculate...

Hille, Bertil

336

The Permeability of the Sodium Channel to Metal Cations in Myelinated Nerve  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The relative permeability of sodium channels to eight metal cations is studied in myelinated nerve fibers. Ionic currents under voltage-clamp conditions are measured in Na-free solutions containing the test ion. Measured reversal potentials and the Goldman equation are used to calculate the permeab...

Hille, Bertil

337

The crystal structure of myelin oligodendrocyte glycoprotein, a key autoantigen in multiple sclerosis  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Myelin oligodendrocyte glycoprotein (MOG) is a key CNS-specific autoantigen for primary demyelination in multiple sclerosis. Although the disease-inducing role of MOG has been established, its precise function in the CNS remains obscure. To gain new insights into the physiological and immunopatholog...

Clements, Craig S.; Reid, Hugh H.; Beddoe, Travis; Tynan, Fleur E.; Perugini, Matthew A.; Johns, Terrance G.; Bernard, Claude C. A.

338

Antisera to different glycolipids induce myelin alterations in mouse spinal cord tissue cultures.  

UK PubMed Central (United Kingdom)

To study the demyelinative effects of antibodies to glycolipids, well-myelinated cultures of mouse spinal cord tissue were exposed to antisera against galactocerebroside and two gangliosides (GM1 and GM4), as well as to anti-white matter antiserum. The demyelinative process was evaluated by morphologic and biochemical techniques. Cultures exposed to anti-white matter and anti-galactocerebroside antisera showed the most marked changes. These consisted of a decrease in the number of oligodendroglial cells and dissolution and phagocytosis of myelin. Concomitantly, the activity of 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNPase) was decreased by 60-70%. This occurred within 24 h of exposure to a relatively low concentration of serum (10%). Cultures exposed to anti-GM1 and anti-GM4 antisera showed similar changes but to a lesser degree. The CNPase activity was decreased about 30% within 48 h of exposure to a 25% concentration of these antisera. This diminution represents about a 20% loss of myelin, an observation corroborated by electron microscopy where myelin but not oligodendroglial cell loss was observed. Therefore, in addition to anti-galactocerebroside activity, which was previously found to be the major antibody responsible for the demyelinating activity induced by anti-whole CNS tissue antiserum, these data suggest that antibodies to gangliosides like GM1 and GM4 might also play a role in immune-mediated demyelination, including perhaps, the human demyelinating diseases.

Roth GA; Röyttä M; Yu RK; Raine CS; Bornstein MB

1985-07-01

339

Ultrastructural Changes in the Myelinated Nerve Fibers of the Sciatic Nerve in Galactose Intoxication in Rats  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The objectives were to study the ultrastructural changes in the myelinated nerve fibers in an animal model of galactosaemia. The study was done in the Anatomy Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia. Twenty-four adult male albino rats were used (6 control and 12...

Faris M. Altaf

340

Characterization of binding properties of the myelin-associated glycoprotein to extracellular matrix constituents.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The myelin-associated glycoprotein (MAG) can be obtained from adult mouse brain from detergent-lysates of a crude membrane fraction as a 96-100 kd form (detergent solubilized MAG), and from 100,000 g supernatants of homogenates as a 90-96 kd form (soluble MAG). The soluble form distributes into the ...

Fahrig, T; Landa, C; Pesheva, P; Kühn, K; Schachner, M

 
 
 
 
341

Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The progressive loss of CNS myelin in patients with multiple sclerosis (MS) has been proposed to result from the combined effects of damage to oligodendrocytes and failure of remyelination. A common feature of demyelinated lesions is the presence of oligodendrocyte precursors (OLPs) blocked at a pre...

Fancy, Stephen P.J.; Baranzini, Sergio E.; Zhao, Chao; Yuk, Dong-In; Irvine, Karen-Amanda; Kaing, Sovann; Sanai, Nader

342

Aging of myelinating glial cells predominantly affects lipid metabolism and immune response pathways.  

UK PubMed Central (United Kingdom)

Both the central and the peripheral nervous systems are prone to multiple age-dependent neurological deficits, often attributed to still unknown alterations in the function of myelinating glia. To uncover the biological processes affected in glial cells by aging, we analyzed gene expression of the Schwann cell-rich mouse sciatic nerve at 17 time points throughout life, from day of birth until senescence. By combining these data with the gene expression data of myelin mouse mutants carrying deletions of either Pmp22, SCAP, or Lpin1, we found that the majority of age-related transcripts were also affected in myelin mutants (54.4%) and were regulated during PNS development (59.5%), indicating a high level of overlap in implicated molecular pathways. The expression profiles in aging copied the direction of transcriptional changes observed in neuropathy models; however, they had the opposite direction when compared with PNS development. The most significantly altered biological processes in aging involved the inflammatory/immune response and lipid metabolism. Interestingly, both these pathways were comparably changed in the aging optic nerve, suggesting that similar biological processes are affected in aging of glia-rich parts of the central and peripheral nervous systems. Our comprehensive comparison of gene expression in three distinct biological conditions including development, aging, and myelin disease thus revealed a previously unanticipated relationship among themselves and identified lipid metabolism and inflammatory/immune response pathways as potential therapeutical targets to prevent or delay so far incurable age-related and inherited forms of neuropathies.

Verdier V; Csárdi G; de Preux-Charles AS; Médard JJ; Smit AB; Verheijen MH; Bergmann S; Chrast R

2012-05-01

343

Tocopherol derivative TFA-12 promotes myelin repair in experimental models of multiple sclerosis.  

UK PubMed Central (United Kingdom)

Multiple sclerosis (MS) is an inflammatory disease of the CNS that is associated with demyelination and axonal loss, resulting in severe neurological handicap. Current MS therapies mostly target neuroinflammation but have only a little impact on CNS myelin repair. Progress toward treatments that enhance remyelination would therefore represent major advances in MS treatment. Here, we examined the ability of TFA-12, a new synthetic compound belonging to tocopherol long-chain fatty alcohols, to promote oligodendrocyte regeneration and remyelination in experimental models of MS. We showed that TFA-12 significantly ameliorates neurological deficit and severity of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) in mice. Histological evaluation of mouse EAE spinal cords showed that TFA-12 treatment reduces inflammation, astrogliosis, and myelin loss. Additionally, we demonstrated that TFA-12 accelerates remyelination of focal demyelinated lesions induced by lysolecithin injections. We also found that this compound induces the differentiation of oligodendrocyte precursor cells into mature oligodendrocytes through the inhibition of the Notch/Jagged1 signaling pathway. Altogether, our data provide important proof of principle indicating that TFA-12 could be a potential therapeutic compound for myelin repair in MS.

Blanchard B; Heurtaux T; Garcia C; Moll NM; Caillava C; Grandbarbe L; Klosptein A; Kerninon C; Frah M; Coowar D; Baron-Van Evercooren A; Morga E; Heuschling P; Nait Oumesmar B

2013-07-01

344

Transfer of axonally transported phospholipids into myelin isolated from the rabbit optic pathway  

Energy Technology Data Exchange (ETDEWEB)

The contribution of the axonal transport to the biosynthesis of myelin phospholipids was investigated in the rabbit optic pathway. A double labeling technique was used. The same animals were injected with one isotope intravitreally and the other intraventricularly. This procedure allows double labeling of the optic nerves, optic tracts, lateral geniculate bodies (LGB), and superior colliculus (SC). The precursors simultaneously injected were: (1-/sup 14/C)palmitate (15 microCi intravitreally in both eyes or 50 microCi intraventricularly) and (2-/sup 3/H)glycerol (50 microCi intravitreally in both eyes of 100 microCi intraventricularly). Twenty four hours and 10 days after the injections, myelin was purified from pooled optic nerves and optic tracts as well as from pooled LGBs or SCs. The phospholipids were extracted and then separated by thin-layer chromatography; the specific radioactivity of the various classes of phospholipids was determined. Using both administration routes of C- or /sup 3/H-precursors, the distribution of label and specific radioactivity of myelin phospholipids in the retina and in all other optic structures were very similar. Phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine + phosphoinositol were preferentially labeled with both precursors. These results suggest that, in the rabbit optic pathway the phospholipids synthesized in the retinal ganglion cells and transported along the axons, could undergo transaxonal transfer into myelin.

Alberghina, M.; Viola, M.; Giuffrida, A.M.

1982-02-01

345

Monocytoid B cell lymphoma associated with antibodies to myelin-associated glycoprotein and sulphated glucuronyl paragloboside.  

UK PubMed Central (United Kingdom)

Monocytoid B cell lymphoma (MBCL) is an immunologically and morphologically well-defined low-grade lymphoma with a predilection for lymph nodes of the parotid region. We describe an association of MBCL with anti-myelin-associated glycoprotein (MAG) polyneuropathy in a 53-year-old male. The diagnosis of stage IV MBCL with nodular bone marrow infiltration, Sjögren's syndrome and sensorimotor polyneuropathy was made in October 1996. Serum immunoelectrophoresis demonstrated IgMkappa paraprotein. This was then cross-reacted with epitopes of MAG and sulphated glucuronyl paragloboside (SGPG) on myelin sheaths, and detected by thin layer chromatography and Western blot. Direct immunofluorescence of a sural nerve biopsy showed loss of myelin fibres, segmental demyelinization and IgM deposits on the myelin sheaths. The cerebrospinal fluid was normal. After six cycles of chemotherapy (ChlVPP protocol), all the patient's haematological parameters normalized accompanied by an improvement in neurological signs. The improvement of the polyneuropathy after chemotherapy indicates that the autoimmune anti-MAG and anti-SGPG antibodies resulted from the neoplastic lymphoid proliferation.

Donfrid M; Apostolski S; Suvajdzi? N; Jankovi? G; Cemeriki?-Martinovi? V; Atkinson HD; Colovic M

2001-01-01

346

Monocytoid B cell lymphoma associated with antibodies to myelin-associated glycoprotein and sulphated glucuronyl paragloboside.  

Science.gov (United States)

Monocytoid B cell lymphoma (MBCL) is an immunologically and morphologically well-defined low-grade lymphoma with a predilection for lymph nodes of the parotid region. We describe an association of MBCL with anti-myelin-associated glycoprotein (MAG) polyneuropathy in a 53-year-old male. The diagnosis of stage IV MBCL with nodular bone marrow infiltration, Sjögren's syndrome and sensorimotor polyneuropathy was made in October 1996. Serum immunoelectrophoresis demonstrated IgMkappa paraprotein. This was then cross-reacted with epitopes of MAG and sulphated glucuronyl paragloboside (SGPG) on myelin sheaths, and detected by thin layer chromatography and Western blot. Direct immunofluorescence of a sural nerve biopsy showed loss of myelin fibres, segmental demyelinization and IgM deposits on the myelin sheaths. The cerebrospinal fluid was normal. After six cycles of chemotherapy (ChlVPP protocol), all the patient's haematological parameters normalized accompanied by an improvement in neurological signs. The improvement of the polyneuropathy after chemotherapy indicates that the autoimmune anti-MAG and anti-SGPG antibodies resulted from the neoplastic lymphoid proliferation. PMID:11713380

Donfrid, M; Apostolski, S; Suvajdzi?, N; Jankovi?, G; Cemeriki?-Martinovi?, V; Atkinson, H D; Colovic, M

2001-01-01

347

beta1-integrin mediates myelin-associated glycoprotein signaling in neuronal growth cones  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Several myelin-associated factors that inhibit axon growth of mature neurons, including Nogo66, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp), can associate with a common GPI-linked protein Nogo-66 receptor (NgR). Accumulating evidence suggests that myelin inhibitors also signal through unknown NgR-independent mechanisms. Here we show that MAG, a RGD tri-peptide containing protein, forms a complex with ?1-integrin to mediate axonal growth cone turning responses of several neuronal types. Mutations that alter the RGD motif in MAG or inhibition of ?1-integrin function, but not removal of NgRs, abolish these MAG-dependent events. In contrast, OMgp-induced repulsion is not affected by inhibition of b1-integrin function. We further show that MAG stimulates tyrosine phosphorylation of focal adhesion kinase (FAK), which in turn is required for MAG-induced growth cone turning. These studies identify ?1-integrin as a specific mediator for MAG in growth cone turning responses, acting through FAK activation.

Goh Eyleen LK; Young Ju; Kuwako Kenichiro; Tessier-Lavigne Marc; He Zhigang; Griffin John W; Ming Guo-li

2008-01-01

348

TRO19622 Promotes Myelin Repair in a rat Model of Demyelination.  

UK PubMed Central (United Kingdom)

Abstract Background/Aims Multiple sclerosis is a neurodegenerative auto-immune disease characterized by diffuse oligodendrocyte injury, axonal loss, and multifocal demyelination of myelin sheaths in the central nervous system. TRO19622 is a small cholesterol-like compound, which displays remarkable neuroprotective and neuroregenerative properties in neural cell culture and rodent models of nerve trauma. Therefore the aim of the present study is to evaluate the pharmacological action of TRO19622 on the demyelination/remyelination processes by using a rat model of cuprizone induced demyelination. Methods Using Female Sprague-Dawley rats models of demyelination, we morphologically and functionally assessed the effect of TRO19622 on myelination in vivo. Results In this study, we first provided in vivo proof that cuprizone intoxication contributed to spatial learning and memory ability injury, and that TRO19622 restored neurological function. The structure of myelin injury and repair in cuprizone intoxication rats was then measured by T2-weighted magnetic resonance imaging. These magnetic resonance imaging based results and trends were confirmed by histological, immunohistochemistry, and electron microscopy analyses. Conclusions The results cleared showed that TRO19622 promoted myelin formation with consequent functional improvement.

Li Y; Zhang Y; Han W; Hu F; Qian Y; Chen Q

2013-05-01

349

Canavan disease and the role of N-acetylaspartate in myelin synthesis.  

Science.gov (United States)

Canavan disease (CD) is an autosomal-recessive neurodegenerative disorder caused by inactivation of the enzyme aspartoacylase (ASPA, EC 3.5.1.15) due to mutations. ASPA releases acetate by deacetylation of N-acetylaspartate (NAA), a highly abundant amino acid derivative in the central nervous system. CD results in spongiform degeneration of the brain and severe psychomotor retardation, and the affected children usually die by the age of 10. The pathogenesis of CD remains a matter of inquiry. Our hypothesis is that ASPA actively participates in myelin synthesis by providing NAA-derived acetate for acetyl CoA synthesis, which in turn is used for synthesis of the lipid portion of myelin. Consequently, CD results from defective myelin synthesis due to a deficiency in the supply of the NAA-derived acetate. The demonstration of the selective localization of ASPA in oligodendrocytes in the central nervous system (CNS) is consistent with the acetate deficiency hypothesis of CD. We have tested this hypothesis by determining acetate levels and studying myelin lipid synthesis in the ASPA gene knockout model of CD, and the results provided the first direct evidence in support of this hypothesis. Acetate supplementation therapy is proposed as a simple and inexpensive therapeutic approach to this fatal disease, and progress in our preclinical efforts toward this goal is presented. PMID:16647192

Namboodiri, Aryan M A; Peethambaran, Arun; Mathew, Raji; Sambhu, Prasanth A; Hershfield, Jeremy; Moffett, John R; Madhavarao, Chikkathur N

2006-05-02

350

THE EFFECTS OF NERVE GROWTH FACTOR ON MYELINATION OF REGENERATED FIBERS IN RAT  

Directory of Open Access Journals (Sweden)

Full Text Available The effect of nerve growth factor (NGF) on regeneration of rat sciatic nerves in adult rat was studied. The sciatic nerve was cut out across a 6?mm gap, then the proximal and distal stumps were inserted into the silicone tube chamber. 7s NGF was extracted from submaxillary gland and then was injected into the silicone in experimental group. After seven months nerve was transected and stained with toluidine blue. Semithin sections (1 µm from middle of silicone (control group, without NGF) showed that regenerated axons (mostly unmyelinated) were dispersed randomly, and they were not grouped into bundles. In this group some of the myelinated fibers were degenerated and macrophages or in other word, schwann cells contained a large amount of these degenerated sheaths. Semithin section of experimental group (with NGF) showed numerous regenerated axons (myelinated) that were grouped into small bundles. Schwann cells in experimental group were large and eucromatin and some of them were divided. These data indicate that NGF causes myelinated axons, regenerate and making new myelinated sheaths.

M. Firouzi

2003-01-01

351

TRO19622 promotes myelin repair in a rat model of demyelination.  

UK PubMed Central (United Kingdom)

Background/Aims: Multiple sclerosis is a neurodegenerative autoimmune disease characterized by diffuse oligodendrocyte injury, axonal loss and multifocal demyelination of myelin sheaths in the central nervous system. TRO19622 is a small cholesterol-like compound, which displays remarkable neuroprotective and neuroregenerative properties in neural cell culture and rodent models of nerve trauma. Therefore, the aim of the present study is to evaluate the pharmacological action of TRO19622 on the demyelination/remyelination processes by using a rat model of cuprizone-induced demyelination. Methods: Using Female Sprague-Dawley rats models of demyelination, we morphologically and functionally assessed the effect of TRO19622 on myelination in vivo. Results: In this study, we first provided in vivo proof that cuprizone intoxication contributed to spatial learning and memory ability injury and that TRO19622 restored neurological function. The structure of myelin injury and repair in cuprizone intoxication rats was then measured by T2-weighted magnetic resonance imaging. These magnetic resonance imaging-based results and trends were confirmed by histological, immunohistochemistry and electron microscopy analyses. Conclusions: The results clearly showed that TRO19622 promoted myelin formation with consequent functional improvement.

Li Y; Zhang Y; Han W; Hu F; Qian Y; Chen Q

2013-11-01

352

MYELIN BASIC PROTEIN-MRNA USED TO MONITOR TRIMETHYLTIN TOXIC NEUROPATHY IN RATS  

Science.gov (United States)

Trimethyltin (TMT) is an alkyltin that selectively targets neurons of the limbic system. ene probe (i.e., mRNA) for myelin basic protein (MBP) was used to monitor this toxic neuropathy. prague Dawley rats, were dosed (IP) acutely with hydroxide at neuropathic (8.0 mg/kg) or non-n...

353

Fine-Structural Changes of Myelin Sheaths after Axonal Degeneration in the Spinal Cord of Rats.  

Science.gov (United States)

The myelin sheaths of degenerating axons were studied from 4 to 52 days after section of the ascending dorsal tracts in the thoracic spinal cord of rats. In the peritraumatic region abundant macrophages rapidly engulfed the degenerating axons and their sh...

P. W. Lampert M. R. Cressman

1966-01-01

354

Myelin basic protein determination in cerebro-spinal fluid of children with tuberculous meningitis  

International Nuclear Information System (INIS)

[en] Myelin basic protein (MBP), an indicator of neural tissue damage in cerebro-spinal fluid, was studied in patients with tuberculous meningitis (TBM). MBP levels were elevated in 62% of the cases of TBM, the levels being 13.3+-18.8 ng/mL, compared with control levels of 1.34+-0.55 ng/mL(p

1986-01-01

355

Compressed sensing CPMG with group-sparse reconstruction for myelin water imaging.  

UK PubMed Central (United Kingdom)

PURPOSE: Myelin content is a marker for nervous system pathology and is quantifiable by myelin water imaging using multi-echo CPMG sequence, which is inherently slow. One way to accelerate the scan is to utilize compressed sensing. However, reconstructing the images piecemeal by standard compressed sensing methods is not the optimal solution, because it only exploits intraimage spatial redundancy. It does not recognize that the different T2 weighted images are scans of the same anatomical volume and hence correlated. The purpose of this work is to test the feasibility of compressed sensed CPMG with group-sparsity promoting optimization for myelin water imaging. METHODS: Group-sparse reconstruction was performed at various simulated and actual undersampling factors for an electronic phantom, ex vivo rat spinal cord, and in vivo rat spinal cord. Normalized mean square error was used as the metric for comparison. RESULTS: For both simulated undersampling and the actual undersampling, the method was found to minimally impact myelin water fraction map quality (normalized mean square error?

Chen HS; Majumdar A; Kozlowski P

2013-06-01

356

Compressed sensing CPMG with group-sparse reconstruction for myelin water imaging.  

Science.gov (United States)

PURPOSE: Myelin content is a marker for nervous system pathology and is quantifiable by myelin water imaging using multi-echo CPMG sequence, which is inherently slow. One way to accelerate the scan is to utilize compressed sensing. However, reconstructing the images piecemeal by standard compressed sensing methods is not the optimal solution, because it only exploits intraimage spatial redundancy. It does not recognize that the different T2 weighted images are scans of the same anatomical volume and hence correlated. The purpose of this work is to test the feasibility of compressed sensed CPMG with group-sparsity promoting optimization for myelin water imaging. METHODS: Group-sparse reconstruction was performed at various simulated and actual undersampling factors for an electronic phantom, ex vivo rat spinal cord, and in vivo rat spinal cord. Normalized mean square error was used as the metric for comparison. RESULTS: For both simulated undersampling and the actual undersampling, the method was found to minimally impact myelin water fraction map quality (normalized mean square error?

Chen, Henry S; Majumdar, Angshul; Kozlowski, Piotr

2013-06-14

357

Myelin protein zero gene mutated in Charcot-Marie-tooth type 1B patients.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Autosomal dominant of Charcot-Marie-Tooth disease (CMT), whose gene is type 1B (CMT1B), has slow nerve conduction with demyelinated Schwann cells. In this study the abundant peripheral myelin protein zero (MPZ) gene, MPZ, was mapped 130 kb centromeric to the Fc receptor immunoglobulin gene cluster i...

Su, Y; Brooks, D G; Li, L; Lepercq, J; Trofatter, J A; Ravetch, J V; Lebo, R V

358

Tocopherol derivative TFA-12 promotes myelin repair in experimental models of multiple sclerosis.  

Science.gov (United States)

Multiple sclerosis (MS) is an inflammatory disease of the CNS that is associated with demyelination and axonal loss, resulting in severe neurological handicap. Current MS therapies mostly target neuroinflammation but have only a little impact on CNS myelin repair. Progress toward treatments that enhance remyelination would therefore represent major advances in MS treatment. Here, we examined the ability of TFA-12, a new synthetic compound belonging to tocopherol long-chain fatty alcohols, to promote oligodendrocyte regeneration and remyelination in experimental models of MS. We showed that TFA-12 significantly ameliorates neurological deficit and severity of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) in mice. Histological evaluation of mouse EAE spinal cords showed that TFA-12 treatment reduces inflammation, astrogliosis, and myelin loss. Additionally, we demonstrated that TFA-12 accelerates remyelination of focal demyelinated lesions induced by lysolecithin injections. We also found that this compound induces the differentiation of oligodendrocyte precursor cells into mature oligodendrocytes through the inhibition of the Notch/Jagged1 signaling pathway. Altogether, our data provide important proof of principle indicating that TFA-12 could be a potential therapeutic compound for myelin repair in MS. PMID:23843531

Blanchard, Benoit; Heurtaux, Tony; Garcia, Corina; Moll, Natalia M; Caillava, Céline; Grandbarbe, Luc; Klosptein, Armelle; Kerninon, Christophe; Frah, Magali; Coowar, Djalil; Baron-Van Evercooren, Anne; Morga, Eleonora; Heuschling, Paul; Nait Oumesmar, Brahim

2013-07-10

359

Simultaneous very thick split-thickness and split-thickness skin grafting for treating burned limbs.  

UK PubMed Central (United Kingdom)

To achieve the goals of burn wound coverage and prevention of burn scar contracture, the author applied very thick split-thickness (to mobile surfaces) and ordinary split-thickness (to nonmobile surfaces) skin grafting to burned wounds simultaneously. Using a Padgett dermatome to harvest very thick split-thickness skin (0.024-0.026 in) is a simple and time-saving procedure. The initial results were good and patients had a better outcome and shorter home stay before resuming work.

Tang YW

2010-09-01

360

Replacement of split-pin assemblies in nuclear reactors  

Energy Technology Data Exchange (ETDEWEB)

This patent describes a pin-insertion/torque tool for the replacement of old split-pin assemblies. Each of the new split-pin assemblies including a new split-pin having times and a new nut for securing the new split pin in the guide tube, a new nut being inserted in the guide tube in position to receive a split pin. The the pin-insertion/torque tool including a blade means for engaging a new split pin with the blade with the tines of the new split pins straddling the blade, means, connected to the blade, for advancing the split-pin into the guide tube into threading engagement with the new nut positioned to receive a new split pin and means, to be connected to the nut for securing the new nut onto the new split pin while the split pin is engaged by the blade.

Nee, J.D.; Green, R.A.

1989-12-12

 
 
 
 
361

Reduced inflammation accompanies diminished myelin damage and repair in the NG2 null mouse spinal cord  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Multiple sclerosis (MS) is a demyelinating disease in which blood-derived immune cells and activated microglia damage myelin in the central nervous system. While oligodendrocyte progenitor cells (OPCs) are essential for generating oligodendrocytes for myelin repair, other cell types also participate in the damage and repair processes. The NG2 proteoglycan is expressed by OPCs, pericytes, and macrophages/microglia. In this report we investigate the effects of NG2 on these cell types during spinal cord demyelination/remyelination. Methods Demyelinated lesions were created by microinjecting 1% lysolecithin into the lumbar spinal cord. Following demyelination, NG2 expression patterns in wild type mice were studied via immunostaining. Immunolabeling was also used in wild type and NG2 null mice to compare the extent of myelin damage, the kinetics of myelin repair, and the respective responses of OPCs, pericytes, and macrophages/microglia. Cell proliferation was quantified by studies of BrdU incorporation, and cytokine expression levels were evaluated using qRT-PCR. Results The initial volume of spinal cord demyelination in wild type mice is twice as large as in NG2 null mice. However, over the ensuing 5 weeks there is a 6-fold improvement in myelination in wild type mice, versus only a 2-fold improvement in NG2 null mice. NG2 ablation also results in reduced numbers of each of the three affected cell types. BrdU incorporation studies reveal that reduced cell proliferation is an important factor underlying NG2-dependent decreases in each of the three key cell populations. In addition, NG2 ablation reduces macrophage/microglial cell migration and shifts cytokine expression from a pro-inflammatory to anti-inflammatory phenotype. Conclusions Loss of NG2 expression leads to decreased proliferation of OPCs, pericytes, and macrophages/microglia, reducing the abundance of all three cell types in demyelinated spinal cord lesions. As a result of these NG2-dependent changes, the course of demyelination and remyelination in NG2 null mice differs from that seen in wild type mice, with both myelin damage and repair being reduced in the NG2 null mouse. These studies identify NG2 as an important factor in regulating myelin processing, suggesting that therapeutic targeting of the proteoglycan might offer a means of manipulating cell behavior in demyelinating diseases.

Kucharova Karolina; Chang Yunchao; Boor Andrej; Yong Voon; Stallcup William B

2011-01-01

362

SWI/SNF enzymes promote SOX10- mediated activation of myelin gene expression.  

Science.gov (United States)

SOX10 is a Sry-related high mobility (HMG)-box transcriptional regulator that promotes differentiation of neural crest precursors into Schwann cells, oligodendrocytes, and melanocytes. Myelin, formed by Schwann cells in the peripheral nervous system, is essential for propagation of nerve impulses. SWI/SNF complexes are ATP dependent chromatin remodeling enzymes that are critical for cellular differentiation. It was recently demonstrated that the BRG1 subunit of SWI/SNF complexes activates SOX10 expression and also interacts with SOX10 to activate expression of OCT6 and KROX20, two transcriptional regulators of Schwann cell differentiation. To determine the requirement for SWI/SNF enzymes in the regulation of genes that encode components of myelin, which are downstream of these transcriptional regulators, we introduced SOX10 into fibroblasts that inducibly express dominant negative versions of the SWI/SNF ATPases, BRM or BRG1. Dominant negative BRM and BRG1 have mutations in the ATP binding site and inhibit gene activation events that require SWI/SNF function. Ectopic expression of SOX10 in cells derived from NIH 3T3 fibroblasts led to the activation of the endogenous Schwann cell specific gene, myelin protein zero (MPZ) and the gene that encodes myelin basic protein (MBP). Thus, SOX10 reprogrammed these cells into myelin gene expressing cells. Ectopic expression of KROX20 was not sufficient for activation of these myelin genes. However, KROX20 together with SOX10 synergistically activated MPZ and MBP expression. Dominant negative BRM and BRG1 abrogated SOX10 mediated activation of MPZ and MBP and synergistic activation of these genes by SOX10 and KROX20. SOX10 was required to recruit BRG1 to the MPZ locus. Similarly, in immortalized Schwann cells, BRG1 recruitment to SOX10 binding sites at the MPZ locus was dependent on SOX10 and expression of dominant negative BRG1 inhibited expression of MPZ and MBP in these cells. Thus, SWI/SNF enzymes cooperate with SOX10 to directly activate genes that encode components of peripheral myelin. PMID:23874858

Marathe, Himangi G; Mehta, Gaurav; Zhang, Xiaolu; Datar, Ila; Mehrotra, Aanchal; Yeung, Kam C; de la Serna, Ivana L

2013-07-16

363

SWI/SNF Enzymes Promote SOX10- Mediated Activation of Myelin Gene Expression.  

UK PubMed Central (United Kingdom)

SOX10 is a Sry-related high mobility (HMG)-box transcriptional regulator that promotes differentiation of neural crest precursors into Schwann cells, oligodendrocytes, and melanocytes. Myelin, formed by Schwann cells in the peripheral nervous system, is essential for propagation of nerve impulses. SWI/SNF complexes are ATP dependent chromatin remodeling enzymes that are critical for cellular differentiation. It was recently demonstrated that the BRG1 subunit of SWI/SNF complexes activates SOX10 expression and also interacts with SOX10 to activate expression of OCT6 and KROX20, two transcriptional regulators of Schwann cell differentiation. To determine the requirement for SWI/SNF enzymes in the regulation of genes that encode components of myelin, which are downstream of these transcriptional regulators, we introduced SOX10 into fibroblasts that inducibly express dominant negative versions of the SWI/SNF ATPases, BRM or BRG1. Dominant negative BRM and BRG1 have mutations in the ATP binding site and inhibit gene activation events that require SWI/SNF function. Ectopic expression of SOX10 in cells derived from NIH 3T3 fibroblasts led to the activation of the endogenous Schwann cell specific gene, myelin protein zero (MPZ) and the gene that encodes myelin basic protein (MBP). Thus, SOX10 reprogrammed these cells into myelin gene expressing cells. Ectopic expression of KROX20 was not sufficient for activation of these myelin genes. However, KROX20 together with SOX10 synergistically activated MPZ and MBP expression. Dominant negative BRM and BRG1 abrogated SOX10 mediated activation of MPZ and MBP and synergistic activation of these genes by SOX10 and KROX20. SOX10 was required to recruit BRG1 to the MPZ locus. Similarly, in immortalized Schwann cells, BRG1 recruitment to SOX10 binding sites at the MPZ locus was dependent on SOX10 and expression of dominant negative BRG1 inhibited expression of MPZ and MBP in these cells. Thus, SWI/SNF enzymes cooperate with SOX10 to directly activate genes that encode components of peripheral myelin.

Marathe HG; Mehta G; Zhang X; Datar I; Mehrotra A; Yeung KC; de la Serna IL

2013-01-01

364

Galectin-3 drives oligodendrocyte differentiation to control myelin integrity and function  

Science.gov (United States)

Galectins control critical pathophysiological processes, including the progression and resolution of central nervous system (CNS) inflammation. In spite of considerable progress in dissecting their role within lymphoid organs, their functions within the inflamed CNS remain elusive. Here, we investigated the role of galectin–glycan interactions in the control of oligodendrocyte (OLG) differentiation, myelin integrity and function. Both galectin-1 and -3 were abundant in astrocytes and microglia. Although galectin-1 was abundant in immature but not in differentiated OLGs, galectin-3 was upregulated during OLG differentiation. Biochemical analysis revealed increased activity of metalloproteinases responsible for cleaving galectin-3 during OLG differentiation and modulating its biological activity. Exposure to galectin-3 promoted OLG differentiation in a dose- and carbohydrate-dependent fashion consistent with the ‘glycosylation signature' of immature versus differentiated OLG. Accordingly, conditioned media from galectin-3-expressing, but not galectin-3-deficient (Lgals3?/?) microglia, successfully promoted OLG differentiation. Supporting these findings, morphometric analysis showed a significant decrease in the frequency of myelinated axons, myelin turns (lamellae) and g-ratio in the corpus callosum and striatum of Lgals3?/? compared with wild-type (WT) mice. Moreover, the myelin structure was loosely wrapped around the axons and less smooth in Lgals3?/? mice versus WT mice. Behavior analysis revealed decreased anxiety in Lgals3?/? mice similar to that observed during early demyelination induced by cuprizone intoxication. Finally, commitment toward the oligodendroglial fate was favored in neurospheres isolated from WT but not Lgals3?/? mice. Hence, glial-derived galectin-3, but not galectin-1, promotes OLG differentiation, thus contributing to myelin integrity and function with critical implications in the recovery of inflammatory demyelinating disorders.

Pasquini, L A; Millet, V; Hoyos, H C; Giannoni, J P; Croci, D O; Marder, M; Liu, F T; Rabinovich, G A; Pasquini, J M

2011-01-01

365

Age-related decline of myelin proteins is highly correlated with activation of astrocytes and microglia in the rat CNS.  

Science.gov (United States)

It has been shown that aging can greatly influence the integrity and ultrastructure of white matter and the myelin sheath; however, studies regarding the effects of aging on the expression of myelin proteins are still limited. In the present study, immunohistochemical mapping was used to investigate the overall expression of myelin basic protein (Mbp) and myelin oligodendrocyte glycoprotein (Mog) in the central nervous system (CNS) of rats in postnatal months 2, 5, 18 and 26. Astrocyte and microglia activation was also detected by glial fibrillary acidic protein (GFAP) or ionized calcium-binding adaptor molecule 1 (Iba1) staining and western blotting. A significant decline of Mbp and Mog was identified as a universal alteration in the CNS of aged rats. Aging also induced significant astrocyte and microglial activation. Correlation analysis indicated a negative correlation between the reduction of age?related myelin proteins and glial activation in aging. This correlation of myelin breakdown and glial activation in aging may reveal new evidence in connecting the inflammation and myelin breakdown mechanism of age?related neurodegenerative diseases. PMID:24026164

Xie, Fang; Zhang, Jiu-Cong; Fu, Han; Chen, Jun

2013-09-11

366

Mapping human cortical areas in vivo based on myelin content as revealed by T1- and T2-weighted MRI.  

UK PubMed Central (United Kingdom)

Noninvasively mapping the layout of cortical areas in humans is a continuing challenge for neuroscience. We present a new method of mapping cortical areas based on myelin content as revealed by T1-weighted (T1w) and T2-weighted (T2w) MRI. The method is generalizable across different 3T scanners and pulse sequences. We use the ratio of T1w/T2w image intensities to eliminate the MR-related image intensity bias and enhance the contrast to noise ratio for myelin. Data from each subject were mapped to the cortical surface and aligned across individuals using surface-based registration. The spatial gradient of the group average myelin map provides an observer-independent measure of sharp transitions in myelin content across the surface--i.e., putative cortical areal borders. We found excellent agreement between the gradients of the myelin maps and the gradients of published probabilistic cytoarchitectonically defined cortical areas that were registered to the same surface-based atlas. For other cortical regions, we used published anatomical and functional information to make putative identifications of dozens of cortical areas or candidate areas. In general, primary and early unimodal association cortices are heavily myelinated and higher, multimodal, association cortices are more lightly myelinated, but there are notable exceptions in the literature that are confirmed by our results. The overall pattern in the myelin maps also has important correlations with the developmental onset of subcortical white matter myelination, evolutionary cortical areal expansion in humans compared with macaques, postnatal cortical expansion in humans, and maps of neuronal density in non-human primates.

Glasser MF; Van Essen DC

2011-08-01

367

Self-dual Yang-Mills Equations in Split Signature  

CERN Multimedia

We study the self-dual Yang-Mills equations in split signature. We give a special solution, called the basic split instanton, and describe the ADHM construction in the split signature. Moreover a split version of t'Hooft ansatz is described.

Aryapoor, Masood

2009-01-01

368

Ecological recovery technique for bamboo splits grid  

UK PubMed Central (United Kingdom)

The invention relates to an ecological restoration technique for rock or earth-rock side slopes of highways by using bamboo split fences. The technique comprises a bamboo split fence protection technique and a surface soil backfilling technique, wherein the bamboo split fence technique is to form V-shaped plaint grooves on slope surfaces every 100 centimeters along a horizontal direction with bamboo split sheets and fixed piles and to set No. 12 chain link mesh every 200 meters along a longitudinal direction to for an integral protection system and accordingly realize ecological slope protection. The surface soil backfilling and fixing technique which belongs to a soil dressing technique is to uniformly mixe waste surface soil resource with local straw, rice hulls, slow-release fertilizers, and other support materials and backfill the mixture. With the combination of the two techniques, the bamboo split fence, as time goes on, will form an organic integral with the surface soil filled back and become an organic fertilizer after thousands of years. The surface soil filled back can provide various original ecological communities of animals, plants, microorganisms, etc. to restore the ecology of the slopes. The planted original soil and wild plants speed the succession process of vegetation.

HANZHONG YANG; WANQUAN MA; CHUNXIA LIU; KANGJIAN SHEN; RENZHONG CHEN; ZIXIANG YU

369

A critical role for the cholesterol-associated proteolipids PLP and M6B in myelination of the central nervous system.  

UK PubMed Central (United Kingdom)

The formation of central nervous system myelin by oligodendrocytes requires sterol synthesis and is associated with a significant enrichment of cholesterol in the myelin membrane. However, it is unknown how oligodendrocytes concentrate cholesterol above the level found in nonmyelin membranes. Here, we demonstrate a critical role for proteolipids in cholesterol accumulation. Mice lacking the most abundant myelin protein, proteolipid protein (PLP), are fully myelinated, but PLP-deficient myelin exhibits a reduced cholesterol content. We therefore hypothesized that "high cholesterol" is not essential in the myelin sheath itself but is required for an earlier step of myelin biogenesis that is fully compensated for in the absence of PLP. We also found that a PLP-homolog, glycoprotein M6B, is a myelin component of low abundance. By targeting the Gpm6b-gene and crossbreeding, we found that single-mutant mice lacking either PLP or M6B are fully myelinated, while double mutants remain severely hypomyelinated, with enhanced neurodegeneration and premature death. As both PLP and M6B bind membrane cholesterol and associate with the same cholesterol-rich oligodendroglial membrane microdomains, we suggest a model in which proteolipids facilitate myelination by sequestering cholesterol. While either proteolipid can maintain a threshold level of cholesterol in the secretory pathway that allows myelin biogenesis, lack of both proteolipids results in a severe molecular imbalance of prospective myelin membrane. However, M6B is not efficiently sorted into mature myelin, in which it is 200-fold less abundant than PLP. Thus, only PLP contributes to the high cholesterol content of myelin by association and co-transport.

Werner HB; Krämer-Albers EM; Strenzke N; Saher G; Tenzer S; Ohno-Iwashita Y; De Monasterio-Schrader P; Möbius W; Moser T; Griffiths IR; Nave KA

2013-04-01

370

Lysosomal delivery of the major myelin glycoprotein in the absence of myelin assembly: posttranslational regulation of the level of expression by Schwann cells  

International Nuclear Information System (INIS)

The major myelin protein, P0, has been shown to have decreased levels of expression and altered oligosaccharide processing after the disruption of Schwann cell-axon interaction. We show here that lysosomal degradation of the glycoprotein shortly after its synthesis accounts for much of its decreased expression in the permanently transected adult rat sciatic nerve, a denervated preparation where there is no axonal regeneration or myelin assembly. If [3H]mannose incorporation into sciatic nerve endoneurial slices is examined in the presence of the lysosomotropic agent, NH4Cl, a marked increase in the level of newly synthesized P0 is seen. Pulse-chase analysis of [3H]mannose-labeled P0 in the presence of NH4Cl indicates that this increase is a consequence of inhibition of P0 degradation that normally occurs 1-2 h after biosynthesis in the transected nerve. P0 degradation can also be inhibited if lysosomal function is disturbed by dilation of secondary lysosomes with L-methionine methyl ester. The addition of deoxymannonojirimycin or swainsonine (SW), inhibitors of oligosaccharide-processing mannosidases I and II, respectively, also results in a decrease in P0 degradation. This inhibition is presumably caused by a blockage of transport to the lysosomes due to altered processing of the glycoprotein, although the direct inhibition of lysosomal mannosidases cannot be excluded. In contrast to the transected nerve, addition of NH4Cl or SW has no effect on P0 levels in the crushed nerve, where myelin assembly occurs. The delivery of P0 to the lysosomes of the transected nerve Schwann cells does not appear to be triggered by the mannose-6-phosphate transport system involved in acid hydrolase routing.

1987-01-01

371

Lysosomal delivery of the major myelin glycoprotein in the absence of myelin assembly: posttranslational regulation of the level of expression by Schwann cells  

Energy Technology Data Exchange (ETDEWEB)

The major myelin protein, P0, has been shown to have decreased levels of expression and altered oligosaccharide processing after the disruption of Schwann cell-axon interaction. We show here that lysosomal degradation of the glycoprotein shortly after its synthesis accounts for much of its decreased expression in the permanently transected adult rat sciatic nerve, a denervated preparation where there is no axonal regeneration or myelin assembly. If (/sup 3/H)mannose incorporation into sciatic nerve endoneurial slices is examined in the presence of the lysosomotropic agent, NH/sub 4/Cl, a marked increase in the level of newly synthesized P0 is seen. Pulse-chase analysis of (/sup 3/H)mannose-labeled P0 in the presence of NH/sub 4/Cl indicates that this increase is a consequence of inhibition of P0 degradation that normally occurs 1-2 h after biosynthesis in the transected nerve. P0 degradation can also be inhibited if lysosomal function is disturbed by dilation of secondary lysosomes with L-methionine methyl ester. The addition of deoxymannonojirimycin or swainsonine (SW), inhibitors of oligosaccharide-processing mannosidases I and II, respectively, also results in a decrease in P0 degradation. This inhibition is presumably caused by a blockage of transport to the lysosomes due to altered processing of the glycoprotein, although the direct inhibition of lysosomal mannosidases cannot be excluded. In contrast to the transected nerve, addition of NH/sub 4/Cl or SW has no effect on P0 levels in the crushed nerve, where myelin assembly occurs. The delivery of P0 to the lysosomes of the transected nerve Schwann cells does not appear to be triggered by the mannose-6-phosphate transport system involved in acid hydrolase routing.

Brunden, K.R.; Poduslo, J.F.

1987-03-01

372

Multiple spectral splits of supernova neutrinos.  

UK PubMed Central (United Kingdom)

Collective oscillations of supernova neutrinos swap the spectra f(nu(e))(E) and f(nu[over ](e))(E) with those of another flavor in certain energy intervals bounded by sharp spectral splits. This phenomenon is far more general than previously appreciated: typically one finds one or more swaps and accompanying splits in the nu and nu[over ] channels for both inverted and normal neutrino mass hierarchies. Depending on an instability condition, swaps develop around spectral crossings (energies where f(nu(e))=f(nu(x)), f(nu[over ](e))=f(nu[over ](x)) as well as E-->infinity where all fluxes vanish), and the widths of swaps are determined by the spectra and fluxes. Washout by multiangle decoherence varies across the spectrum and splits can survive as sharp spectral features.

Dasgupta B; Dighe A; Raffelt GG; Smirnov AY

2009-07-01

373

Multiple spectral splits of supernova neutrinos.  

Science.gov (United States)

Collective oscillations of supernova neutrinos swap the spectra f(nu(e))(E) and f(nu[over ](e))(E) with those of another flavor in certain energy intervals bounded by sharp spectral splits. This phenomenon is far more general than previously appreciated: typically one finds one or more swaps and accompanying splits in the nu and nu[over ] channels for both inverted and normal neutrino mass hierarchies. Depending on an instability condition, swaps develop around spectral crossings (energies where f(nu(e))=f(nu(x)), f(nu[over ](e))=f(nu[over ](x)) as well as E-->infinity where all fluxes vanish), and the widths of swaps are determined by the spectra and fluxes. Washout by multiangle decoherence varies across the spectrum and splits can survive as sharp spectral features. PMID:19792481

Dasgupta, Basudeb; Dighe, Amol; Raffelt, Georg G; Smirnov, Alexei Yu

2009-07-31

374

Optimizing phylogenetic networks for circular split systems.  

UK PubMed Central (United Kingdom)

We address the problem of realizing a given distance matrix by a planar phylogenetic network with a minimum number of faces. With the help of the popular software SplitsTree4, we start by approximating the distance matrix with a distance metric that is a linear combination of circular splits. The main results of this paper are the necessary and sufficient conditions for the existence of a network with a single face. We show how such a network can be constructed, and we present a heuristic for constructing a network with few faces using the first algorithm as the base case. Experimental results on biological data show that this heuristic algorithm can produce phylogenetic networks with far fewer faces than the ones computed by SplitsTree4, without affecting the approximation of the distance matrix.

Phipps P; Bereg S

2012-01-01

375

Optimizing phylogenetic networks for circular split systems.  

Science.gov (United States)

We address the problem of realizing a given distance matrix by a planar phylogenetic network with a minimum number of faces. With the help of the popular software SplitsTree4, we start by approximating the distance matrix with a distance metric that is a linear combination of circular splits. The main results of this paper are the necessary and sufficient conditions for the existence of a network with a single face. We show how such a network can be constructed, and we present a heuristic for constructing a network with few faces using the first algorithm as the base case. Experimental results on biological data show that this heuristic algorithm can produce phylogenetic networks with far fewer faces than the ones computed by SplitsTree4, without affecting the approximation of the distance matrix. PMID:21788677

Phipps, Paul; Bereg, Sergey

2011-07-20

376

Stabilizing Heegaard splittings of toroidal 3-manifolds  

CERN Document Server

Given a 3-manifold containing a separating incompressible torus $T$ and a strongly irreducible Heegaard splitting $V \\cup_S W$ of genus $g$, we obtain an upper bound on the number of stabilizations required for $V \\cup_S W$ to become isotopic to a Heegaard splitting which is an amalgamation along $T$. In particular, if $T$ is a canonical torus in the JSJ decomposition of the manifold, then the number of necessary stabilizations is at most $4g-4$. As a corollary, we obtain an upper bound on the number of stabilizations required for $V \\cup_S W$ and any Heegaard splitting obtained by a Dehn twist of $V \\cup_S W$ along $T$ to become isotopic.

Derby-Talbot, R

2006-01-01

377

Multiple Spectral Splits of Supernova Neutrinos  

CERN Document Server

Collective oscillations of supernova neutrinos swap the electron neutrino and antineutrino spectra with those of another flavor in certain energy intervals bounded by sharp spectral splits. This phenomenon is far more general than previously appreciated: typically one finds one or more swaps and accompanying splits in the neutrino and antineutrino channels for both inverted and normal neutrino mass hierarchies. Depending on an instability condition, swaps develop around spectral crossings (energies where the electron neutrino or antineutrino fluxes are equal to that of another flavor, as well as infinite E where all fluxes vanish), and the widths of swaps are determined by the spectra and fluxes. Wash-out by multi-angle decoherence varies across the spectrum and splits can survive as sharp spectral features.

Dasgupta, Basudeb; Raffelt, Georg G; Smirnov, Alexei Yu

2009-01-01

378

A Split Sprint mission to Mars  

Science.gov (United States)

Comprehensive infrastructure analysis is central to developing architectures necessary to support the Space Exploration Initiative. In the ``Split Sprint'' architecture, the cargo is split from the crew. An efficient low thrust ``slow boat'' is used for the cargo and a high thrust ``sprint'' vehicle is used for the crew. Infrastructure analysis is utilized in developing initial element designs to meet the transportation system requirements of the slit sprint architecture. Infrastructure analysis considers technology availability, launch vehicle volume and lift requirements, on orbit assembly, trajectory design and optimization, system reduncancy requirements and evolutionary capability. The resulting infrastructure includes propulsion system options for the crew and cargo space transfer vehicles. For the cargo, an SP-100 derived nuclear electric propulsion system was developed. For the crew, either a conventional cryogenic (LO2/LH2) propulsion system or nuclear thermal propulsion system is utilized. It is shown that the split sprint mission competes effectively with conventional approaches to the Mars mission.

Shepard, Kyle; Duffey, Jack; D'Annible, Dom; Holdridge, Jeff; Thompson, Walter; Armstrong, Robert C.

1992-01-01

379

Splitting methods for the nonlocal Fowler equation  

CERN Multimedia

We consider a nonlocal scalar conservation law proposed by Andrew C. Fowler to describe the dynamics of dunes, and we develop a numerical procedure based on splitting methods to approximate its solutions. We begin by proving the convergence of the well-known Lie formula, which is an approximation of the exact solution of order one in time. We next use the split-step Fourier method to approximate the continuous problem using the fast Fourier transform and the finite difference method. Our numerical experiments confirm the theoretical results.

Bouharguane, Afaf

2011-01-01

380

Spectral statistics for systems with ray splitting  

International Nuclear Information System (INIS)

[en] A finite reverberant system having a discontinuity in some physical parameter will exhibit the splitting of ray trajectories in the high-frequency limit. It is known that this ray splitting can increase the amount of chaos in the ray trajectories [Couchman et al., Phys. Rev. A 46, 6193 (1992)]. This increase of chaos is expected to reveal itself in the eigenfrequency spectrum as a shift away from Poisson statistics and toward the Gaussian orthogonal ensemble (GOE) statistics of random matrix theory. Numerical results are presented that confirm the predicted shift in the spectral statistics. [Work supported by ONR and DOE.

1995-01-01

 
 
 
 
381

Disruption of Nectin-like 1 cell adhesion molecule leads to delayed axonal myelination in the CNS.  

Science.gov (United States)

Nectin-like 1 (Necl-1) is a neural-specific cell adhesion molecule that is expressed in both the CNS and PNS. Previous in vitro studies suggested that Necl-1 expression is essential for the axon-glial interaction and myelin sheath formation in the PNS. To investigate the in vivo role of Necl-1 in axonal myelination of the developing nervous system, we generated the Necl-1 mutant mice by replacing axons 2-5 with the LacZ reporter gene. Expression studies revealed that Necl-1 is exclusively expressed by neurons in the CNS. Disruption of Necl-1 resulted in developmental delay of axonal myelination in the optic nerve and spinal cord, suggesting that Necl-1 plays an important role in the initial axon-oligodendrocyte recognition and adhesion in CNS myelination. PMID:19036974

Park, Jinsil; Liu, Ben; Chen, Tao; Li, Hong; Hu, Xuemei; Gao, Jing; Zhu, Ying; Zhu, Qiang; Qiang, Boqin; Yuan, Jiangang; Peng, Xiaozhong; Qiu, Mengsheng

2008-11-26

382

Reduced R2' in multiple sclerosis normal appearing white matter and lesions may reflect decreased myelin and iron content.  

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R(2)' is an MRI measure of microscopic magnetic field inhomogeneity, and is increased by the paramagnetic effect of iron and the diamagnetic effect of myelin. R(2)' may detect features of multiple sclerosis (MS) not evident with conventional MRI.

Paling, D; Tozer, D; Wheeler-Kingshott, C; Kapoor, R; Miller, DH; Golay, X

383

Role of endogenous pituitary adenylate cyclase activating polypeptide (PACAP) in myelination of the rodent brain: lessons from PACAP-deficient mice.  

Science.gov (United States)

Pituitary adenylate-cyclase activator polypeptide (PACAP), as a consequence of its effect on the elevation of intracellular cAMP level, strongly influences brain development including myelination. While proliferation of oligodendroglial progenitors is stimulated by PACAP applied in vitro, their differentiation is inhibited. However, the in vivo role of PACAP on myelination has never been examined. In the present study the role of endogenous PACAP in myelination was examined in PACAP-deficient mice, in several areas of the brain with a special attention to the cerebral cortex. In young postnatal and adult mice myelination was studied with immunohistochemistry detecting a protein present in the myelin sheath, the myelin basic protein, with Luxol Fast Blue staining and with electron microscopy. Results obtained in PACAP-deficient mice were compared to age-matched wild type controls. We found that the sequence of myelination in the PACAP-deficient animals was similar to that observed in controls. According to this, in both PACAP-deficient and wild type mice, the somatosensory cortex was myelinated before motor areas that preceded the myelination of associational cortical areas. Archicortical associational areas such as the cingulate cortex were myelinated before neocortical areas. Myelination in the corpus callosum followed the known rostro-caudal direction in both PACAP-deficient and wild type animals, and the ventrolateral part of the corpus callosum was myelinated earlier than the dorsomedial part in both groups. In contrast to the similarity in its sequence, striking difference was found in the onset of myelination that started earlier in PACAP-deficient mice than in wild type controls in all of the examined brain regions, including cerebral archi- and neocortex. The first myelinated axons in each of the examined brain regions were observed earlier in the PACAP-deficient mice than in controls. When age-matched animals of the two groups were compared, density of myelinated fibers in the PACAP-deficient mice was higher than in controls in all of the examined areas. We propose that endogenous PACAP exerts an inhibitory role on myelination in vivo. Since myelin sheath of the central nervous system contains several factors blocking neurite outgrowth, inhibition of myelination by PACAP gives time for axonal development and synapse formation, and therefore, strengthens neuronal plasticity. PMID:21726625

Vincze, András; Reglodi, Dóra; Helyes, Zsuzsanna; Hashimoto, Hitoshi; Shintani, Norihito; Abrahám, Hajnalka

2011-06-24

384

Role of endogenous pituitary adenylate cyclase activating polypeptide (PACAP) in myelination of the rodent brain: lessons from PACAP-deficient mice.  

UK PubMed Central (United Kingdom)

Pituitary adenylate-cyclase activator polypeptide (PACAP), as a consequence of its effect on the elevation of intracellular cAMP level, strongly influences brain development including myelination. While proliferation of oligodendroglial progenitors is stimulated by PACAP applied in vitro, their differentiation is inhibited. However, the in vivo role of PACAP on myelination has never been examined. In the present study the role of endogenous PACAP in myelination was examined in PACAP-deficient mice, in several areas of the brain with a special attention to the cerebral cortex. In young postnatal and adult mice myelination was studied with immunohistochemistry detecting a protein present in the myelin sheath, the myelin basic protein, with Luxol Fast Blue staining and with electron microscopy. Results obtained in PACAP-deficient mice were compared to age-matched wild type controls. We found that the sequence of myelination in the PACAP-deficient animals was similar to that observed in controls. According to this, in both PACAP-deficient and wild type mice, the somatosensory cortex was myelinated before motor areas that preceded the myelination of associational cortical areas. Archicortical associational areas such as the cingulate cortex were myelinated before neocortical areas. Myelination in the corpus callosum followed the known rostro-caudal direction in both PACAP-deficient and wild type animals, and the ventrolateral part of the corpus callosum was myelinated earlier than the dorsomedial part in both groups. In contrast to the similarity in its sequence, striking difference was found in the onset of myelination that started earlier in PACAP-deficient mice than in wild type controls in all of the examined brain regions, including cerebral archi- and neocortex. The first myelinated axons in each of the examined brain regions were observed earlier in the PACAP-deficient mice than in controls. When age-matched animals of the two groups were compared, density of myelinated fibers in the PACAP-deficient mice was higher than in controls in all of the examined areas. We propose that endogenous PACAP exerts an inhibitory role on myelination in vivo. Since myelin sheath of the central nervous system contains several factors blocking neurite outgrowth, inhibition of myelination by PACAP gives time for axonal development and synapse formation, and therefore, strengthens neuronal plasticity.

Vincze A; Reglodi D; Helyes Z; Hashimoto H; Shintani N; Abrahám H

2011-12-01

385

Peculiar and typical oligodendrocytes are involved in an uneven myelination pattern during the ontogeny of the lizard visual pathway.  

Science.gov (United States)

We studied the myelination of the visual pathway during the ontogeny of the lizard Gallotia galloti using immunohistochemical methods to stain the myelin basic protein (MBP) and proteolipid protein (PLP/DM20), and electron microscopy. The staining pattern for the PLP/DM20 and MBP overlapped during the lizard ontogeny and was first observed at E39 in cell bodies and fibers located in the temporal optic nerve, optic chiasm, middle optic tract, and in the stratum album centrale of the optic tectum (OT). The expression of these proteins extended to the nerve fiber layer (NFL) of the temporal retina and to the outer strata of the OT at E40. From hatching onwards, the labeling became stronger and extended to the entire visual pathway. Our ultrastructural data in postnatal and adult animals revealed the presence of both myelinated and unmyelinated retinal ganglion cell axons in all visual areas, with a tendency for the larger axons to show the thicker myelin sheaths. Moreover, two kinds of oligodendrocytes were described: peculiar oligodendrocytes displaying loose myelin sheaths were only observed in the NFL, whereas typical medium electron-dense oligodendrocytes displaying compact myelin sheaths were observed in the rest of the visual areas. The weakest expression of the PLP/DM20 in the NFL of the retina appears to be linked to the loose appearance of its myelin sheaths. We conclude that typical and peculiar oligodendrocytes are involved in an uneven myelination process, which follows a temporo-nasal and rostro-caudal gradient in the retina and ON, and a ventro-dorsal gradient in the OT. PMID:16929522

Santos, Elena; Yanes, Carmen M; Monzón-Mayor, Maximina; del Mar Romero-Alemán, Maria

2006-09-01

386

Effect of long-term aluminum feeding on lipid/phospholipid profiles of rat brain myelin  

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Full Text Available Abstract Effect of long-term (90–100 days) exposure of rats to soluble salt of aluminum (AlCl3) on myelin lipid profile was examined. The long-term exposure to AlCl3 resulted in a 60 % decrease in the total phospholipid (TPL) content while the cholesterol (CHL) content increased by 55 %. Consequently the TPL / CHL molar ratio decreased significantly by 62 %. The phospholipid composition of the myelin membrane changed drastically; the proportion of practically all the phospholipid classes decreased by 32 to 60 % except for phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Of the latter two, proportion of PC was unchanged while PE increased in proportion by 47 %. Quantitatively, all phospholipid classes decreased by from 42 to 76% with no change in the PE content. However the membrane fluidity was not altered in Al-treated rats. Many of the changes we observe here show striking similarities with the reported phospholipid profiles of Alzheimer brains.

Pandya Jignesh D; Dave Kunjan R; Katyare Surendra S

2004-01-01

387

Manipulating antigenic ligand strength to selectively target myelin-reactive CD4+ T cells in EAE.  

UK PubMed Central (United Kingdom)

The development of antigen-specific therapies for the selective tolerization of autoreactive T cells remains the Holy Grail for the treatment of T-cell-mediated autoimmune diseases such as multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). This quest remains elusive, however, as the numerous antigen-specific strategies targeting myelin-specific T cells over the years have failed to result in clinical success. In this review, we revisit the antigen-based therapies used in the treatment of myelin-specific CD4+ T cells in the context of the functional avidity and the strength of signal of the encephalitogenic CD4+ T cell repertoire. In light of differences in activation thresholds, we propose that autoreactive T cells are not all equal, and therefore tolerance induction strategies must incorporate ligand strength in order to be successful in treating EAE and ultimately the human disease MS.

Sabatino JJ Jr; Rosenthal KM; Evavold BD

2010-06-01

388

Manipulating antigenic ligand strength to selectively target myelin-reactive CD4+ T cells in EAE.  

Science.gov (United States)

The development of antigen-specific therapies for the selective tolerization of autoreactive T cells remains the Holy Grail for the treatment of T-cell-mediated autoimmune diseases such as multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). This quest remains elusive, however, as the numerous antigen-specific strategies targeting myelin-specific T cells over the years have failed to result in clinical success. In this review, we revisit the antigen-based therapies used in the treatment of myelin-specific CD4+ T cells in the context of the functional avidity and the strength of signal of the encephalitogenic CD4+ T cell repertoire. In light of differences in activation thresholds, we propose that autoreactive T cells are not all equal