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https://www.readbyqxmd.com/read/28073817/paranodal-dissection-in-chronic-inflammatory-demyelinating-polyneuropathy-with-antineurofascin-155-and-anticontactin-1-antibodies
#1
Haruki Koike, Masato Kadoya, Ken-Ichi Kaida, Shohei Ikeda, Yuichi Kawagashira, Masahiro Iijima, Daisuke Kato, Hidenori Ogata, Ryo Yamasaki, Noriyuki Matsukawa, Jun-Ichi Kira, Masahisa Katsuno, Gen Sobue
OBJECTIVE: To investigate the morphological features of chronic inflammatory demyelinating polyneuropathy (CIDP) with autoantibodies directed against paranodal junctional molecules, particularly focusing on the fine structures of the paranodes. METHODS: We assessed sural nerve biopsy specimens obtained from 9 patients with CIDP with antineurofascin-155 antibodies and 1 patient with anticontactin-1 antibodies. 13 patients with CIDP without these antibodies were also examined to compare pathological findings...
January 10, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28064059/par1-activation-affects-the-neurotrophic-properties-of-schwann-cells
#2
Elena Pompili, Cinzia Fabrizi, Francesca Somma, Virginia Correani, Bruno Maras, Maria Eugenia Schininà, Viviana Ciraci, Marco Artico, Francesco Fornai, Lorenzo Fumagalli
Protease-activated receptor-1 (PAR1) is the prototypic member of a family of four G-protein-coupled receptors that signal in response to extracellular proteases. In the peripheral nervous system, the expression and/or the role of PARs are still poorly investigated. High PAR1 mRNA expression was found in the rat dorsal root ganglia and the signal intensity of PAR1 mRNA increased in response to sciatic nerve transection. In the sciatic nerve, functional PAR1 receptor was reported at the level of non-compacted Schwann cell myelin microvilli of the nodes of Ranvier...
January 4, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28017237/serum-antibodies-targeting-neurons-of-the-monoaminergic-systems-in-guillain-barr%C3%A3-syndrome
#3
Claudia Rink, Angelika Görtzen, Rüdiger W Veh, Harald Prüss
Guillain-Barré syndrome (GBS) is an autoimmune disease with progressive flaccid paralysis of the extremities. Several auto-antibodies have been identified, binding to myelin, gangliosides, astrocytes or proteins at the nodes of Ranvier. Some epitopes are not confined to the peripheral nerve, suggesting that auto-antibodies may also contribute to symptoms of the central nervous system, which are common in GBS and include anxiety, depression, hallucinations, oneiroid psychosis or fatigue. This notion is supported by treating patients with plasma exchange, resulting in improvement of both central and peripheral symptoms...
January 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28008944/amyloid-precursor-protein-modulates-nav1-6-sodium-channel-currents-through-a-go-coupled-jnk-pathway
#4
Shao Li, Xi Wang, Quan-Hong Ma, Wu-Lin Yang, Xiao-Gang Zhang, Gavin S Dawe, Zhi-Cheng Xiao
Amyloid precursor protein (APP), commonly associated with Alzheimer's disease, also marks axonal degeneration. In the recent studies, we demonstrated that APP aggregated at nodes of Ranvier (NORs) in myelinated central nervous system (CNS) axons and interacted with Nav1.6. However, the physiological function of APP remains unknown. In this study, we described reduced sodium current densities in APP knockout hippocampal neurons. Coexpression of APP or its intracellular domains containing a VTPEER motif with Nav1...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28003466/ultrastructural-anatomy-of-nodes-of-ranvier-in-the-peripheral-nervous-system-as-revealed-by-sted-microscopy
#5
Elisa D'Este, Dirk Kamin, Francisco Balzarotti, Stefan W Hell
We used stimulated emission depletion (STED) superresolution microscopy to analyze the nanoscale organization of 12 glial and axonal proteins at the nodes of Ranvier of teased sciatic nerve fibers. Cytoskeletal proteins of the axon (betaIV spectrin, ankyrin G) exhibit a high degree of one-dimensional longitudinal order at nodal gaps. In contrast, axonal and glial nodal adhesion molecules [neurofascin-186, neuron glial-related cell adhesion molecule (NrCAM)] can arrange in a more complex, 2D hexagonal-like lattice but still feature a ∼190-nm periodicity...
December 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27979964/schwannomin-interacting-protein-1-isoform-iqcj-schip1-is-a-multi-partner-ankyrin-and-spectrin-binding-protein-involved-in-the-organization-of-nodes-of-ranvier
#6
Pierre-Marie Martin, Carmen Cifuentes-Diaz, Jérôme Devaux, Marta Garcia, Jocelyne Bureau, Sylvie Thomasseau, Esther Klingler, Jean-Antoine Girault, Laurence Goutebroze
Nodes of Ranvier are essential regions for action potential conduction in myelinated fibers. They are enriched in multimolecular complexes comprised of voltage-gated Nav and Kv7 channels associated with cell adhesion molecules. Cytoskeletal proteins ankyrin-G (AnkG) and βIV-spectrin control the organization of these complexes and provide mechanical support to the plasma membrane. IQCJ-SCHIP1 is a cytoplasmic protein present in axon initial segments and nodes of Ranvier. It interacts with AnkG and is absent from nodes and axon initial segments of βIV-spectrin and AnkG mutant mice...
December 15, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27939751/estimating-axonal-strain-and-failure-following-white-matter-stretch-using-contactin-associated-protein-as-a-fiduciary-marker
#7
Sagar Singh, Assimina A Pelegri, David I Shreiber
Axonal injury occurs during trauma when tissue-scale loads are transferred to individual axons. Computational models are used to understand this transfer and predict the circumstances that cause injury. However, these findings are limited by a lack of validating experimental work examining the mechanics of axons in their in situ state. As a first step towards validation for dynamic stretch, we use contactin-associated protein (Caspr), expressed at the nodes of Ranvier, as a fiduciary marker of quasistatic axonal stretch...
January 25, 2017: Journal of Biomechanics
https://www.readbyqxmd.com/read/27916751/-autoantibodies-in-chronic-inflammatory-neuropathies
#8
Ryo Yamasaki
Autoantibodies in chronic demyelinating neuropathies have been explored for several years. Recently, the peptides in the nodes of Ranvier have been the focus of attention in finding targets of autoantibodies. Until now, the most popular autoantibodies have been contactin-1 and neurofascin-155 for chronic demyelinating polyradiculoneuropathy (CIDP), GM1-ganglioside for multifocal motor neuropathy, and myelin-associated glycoprotein for polyneuropathy associated with monoclonal gammopathy of unknown significance...
December 2016: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/27902705/neuronal-ndrg4-is-essential-for-nodes-of-ranvier-organization-in-zebrafish
#9
Laura Fontenas, Flavia De Santis, Vincenzo Di Donato, Cindy Degerny, Béatrice Chambraud, Filippo Del Bene, Marcel Tawk
Axon ensheathment by specialized glial cells is an important process for fast propagation of action potentials. The rapid electrical conduction along myelinated axons is mainly due to its saltatory nature characterized by the accumulation of ion channels at the nodes of Ranvier. However, how these ion channels are transported and anchored along axons is not fully understood. We have identified N-myc downstream-regulated gene 4, ndrg4, as a novel factor that regulates sodium channel clustering in zebrafish. Analysis of chimeric larvae indicates that ndrg4 functions autonomously within neurons for sodium channel clustering at the nodes...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27889898/the-transcription-factors-ebf1-and-ebf2-are-positive-regulators-of-myelination-in-schwann-cells
#10
Diego Moruzzo, Lucilla Nobbio, Bruno Sterlini, G Giacomo Consalez, Fabio Benfenati, Angelo Schenone, Anna Corradi
Myelin formation by Schwann cells is tightly controlled by multiple pathways and regulatory molecules. The Ebf2 gene, belonging to the Ebf family of transcription factors regulating cell development and differentiation, is expressed in Schwann cells, and Ebf2 knockout mice show peripheral nerve defects. We also found that Ebf1 is expressed in Schwann cells. To investigate Ebf function in myelination, we silenced Ebf genes in myelinating dorsal root ganglia cultures. Combined downregulation of Ebf genes leads to a severe impairment of myelin formation that is completely rescued by their specific overexpression, suggesting that the expression level of Ebf genes strongly influences axon myelination...
November 26, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27866733/review-of-the-literature-articles-published-in-the-last-five-years-that-have-changed-my-daily-practice
#11
REVIEW
E Delmont
Over the last five years, the management of peripheral neuropathies has become structured by the publication of recognized diagnostic criteria for inflammatory neuropathies and the elaboration of a function score, the R-ODS, used to evaluate the progression of these neuropathies. The concept of nodo-paranodopathy has enriched the concept of peripheral neuropathies, over-riding the classical mechanisms of axonal and demyelinating mechanisms. The structures of the nodes of Ranvier, gangliosides, contractin and neurofascin are preferential targets for auto-antibodies responsible for dysimmune neuropathies...
December 2016: Revue Neurologique
https://www.readbyqxmd.com/read/27857121/guillain-barr%C3%A3-syndrome-a-century-of-progress
#12
REVIEW
John A Goodfellow, Hugh J Willison
In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts - novel findings that identified the disease we now know as Guillain-Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise...
November 18, 2016: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/27832602/activity-dependent-formation-and-location-of-voltage-gated-sodium-channel-clusters-at-a-cns-nerve-terminal-during-postnatal-development
#13
Jie Xu, Emmanuelle Berret, Jun Hee Kim
In auditory pathways, the precision of action potential (AP) propagation depends on axon myelination and high densities of voltage-gated Na (Nav) channels clustered at nodes of Ranvier. Changes in Nav channel expression at the heminode, the final node before the nerve terminal, can alter AP invasion into the presynaptic terminal. Here, we studied the activity-dependent formation of Nav channel clusters before and after hearing onset at P12 in the rat and mouse auditory brainstem. In rats, the Nav channel cluster at the heminode formed progressively during the second postnatal week, around hearing onset, whereas the Nav channel cluster at the nodes was present before hearing onset...
November 9, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27818385/contactin-associated-protein-1-cntnap1-mutations-induce-characteristic-lesions-of-the-paranodal-region
#14
Jean-Michel Vallat, Mathilde Nizon, Alex Magee, Bertrand Isidor, Laurent Magy, Yann Péréon, Laurence Richard, Robert Ouvrier, Benjamin Cogné, Jérôme Devaux, Stephan Zuchner, Stéphane Mathis
Congenital hypomyelinating neuropathy is a rare neonatal syndrome responsible for hypotonia and weakness. Nerve microscopic examination shows amyelination or hypomyelination. Recently, mutations in CNTNAP1 have been described in a few patients. CNTNAP1 encodes contactin-associated protein 1 (caspr-1), which is an essential component of the paranodal junctions of the peripheral and central nervous systems, and is necessary for the establishment of transverse bands that stabilize paranodal axo-glial junctions...
November 6, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27771530/thrombin-and-protein-c-pathway-in-peripheral-nerve-schwann-cells
#15
Orna Gera, Efrat Shavit-Stein, Doron Bushi, Sagi Harnof, Marina Ben Shimon, Ronen Weiss, Valery Golderman, Amir Dori, Nicola Maggio, Kate Finegold, Joab Chapman
Thrombin and activated protein C (aPC) bound to the endothelial protein C receptor (EPCR) both activate protease-activated receptor 1 (PAR1) generating either harmful or protective signaling respectively. In the present study we examined the localization of PAR-1 and EPCR and thrombin activity in Schwann glial cells of normal and crushed peripheral nerve and in Schwannoma cell lines. In the sciatic crush model nerves were excised 1h, 1, 4, and 7days after the injury. Schwannoma cell lines produced high levels of prothrombin which is converted to active thrombin and expressed both EPCR and PAR-1 which co-localized...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27717670/formation-and-disruption-of-functional-domains-in-myelinated-cns-axons
#16
Ryan B Griggs, Leonid M Yermakov, Keiichiro Susuki
Communication in the central nervous system (CNS) occurs through initiation and propagation of action potentials at excitable domains along axons. Action potentials generated at the axon initial segment (AIS) are regenerated at nodes of Ranvier through the process of saltatory conduction. Proper formation and maintenance of the molecular structure at the AIS and nodes are required for sustaining conduction fidelity. In myelinated CNS axons, paranodal junctions between the axolemma and myelinating oligodendrocytes delineate nodes of Ranvier and regulate the distribution and localization of specialized functional elements, such as voltage-gated sodium channels and mitochondria...
October 4, 2016: Neuroscience Research
https://www.readbyqxmd.com/read/27666389/fhf-independent-conduction-of-action-potentials-along-the-leak-resistant-cerebellar-granule-cell-axon
#17
Katarzyna Dover, Christopher Marra, Sergio Solinas, Marko Popovic, Sathyaa Subramaniyam, Dejan Zecevic, Egidio D'Angelo, Mitchell Goldfarb
Neurons in vertebrate central nervous systems initiate and conduct sodium action potentials in distinct subcellular compartments that differ architecturally and electrically. Here, we report several unanticipated passive and active properties of the cerebellar granule cell's unmyelinated axon. Whereas spike initiation at the axon initial segment relies on sodium channel (Nav)-associated fibroblast growth factor homologous factor (FHF) proteins to delay Nav inactivation, distal axonal Navs show little FHF association or FHF requirement for high-frequency transmission, velocity and waveforms of conducting action potentials...
September 26, 2016: Nature Communications
https://www.readbyqxmd.com/read/27616481/mutations-in-gldn-encoding-gliomedin-a-critical-component-of-the-nodes-of-ranvier-are-responsible-for-lethal-arthrogryposis
#18
Jérôme Maluenda, Constance Manso, Loic Quevarec, Alexandre Vivanti, Florent Marguet, Marie Gonzales, Fabien Guimiot, Florence Petit, Annick Toutain, Sandra Whalen, Romulus Grigorescu, Anne Dieux Coeslier, Marta Gut, Ivo Gut, Annie Laquerrière, Jérôme Devaux, Judith Melki
Arthrogryposis multiplex congenita (AMC) is a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. Through linkage analysis, homozygosity mapping, and exome sequencing in four unrelated families affected by lethal AMC, we identified biallelic mutations in GLDN in the affected individuals. GLDN encodes gliomedin, a secreted cell adhesion molecule involved in the formation of the nodes of Ranvier. Transmission electron microscopy of the sciatic nerve from one of the affected individuals showed a marked lengthening defect of the nodes...
October 6, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27615452/decrease-in-newly-generated-oligodendrocytes-leads-to-motor-dysfunctions-and-changed-myelin-structures-that-can-be-rescued-by-transplanted-cells
#19
Sarah Schneider, Agnès Gruart, Sofia Grade, Yina Zhang, Stephan Kröger, Frank Kirchhoff, Gregor Eichele, José M Delgado García, Leda Dimou
NG2-glia in the adult brain are known to proliferate and differentiate into mature and myelinating oligodendrocytes throughout lifetime. However, the role of these newly generated oligodendrocytes in the adult brain still remains little understood. Here we took advantage of the Sox10-iCreER(T2) x CAG-eGFP x Esco2(fl/fl) mouse line in which we can specifically ablate proliferating NG2-glia in adult animals. Surprisingly, we observed that the generation of new oligodendrocytes in the adult brain was severely affected, although the number of NG2-glia remained stable due to the enhanced proliferation of non-recombined cells...
September 12, 2016: Glia
https://www.readbyqxmd.com/read/27614087/preferential-conduction-block-of-myelinated-axons-by-nitric-oxide
#20
Peter Shrager, Margaret Youngman
Conduction block by nitric oxide (NO) was examined in myelinated and unmyelinated axons from both the central nervous system and peripheral nervous system. In rat vagus nerves, mouse optic nerves at P12-P23, adult and developing mouse sciatic nerves, and mouse spinal cords, myelinated fibers were preferentially blocked reversibly by concentrations of NO similar to those encountered in inflammatory lesions. The possibility that these differences between myelinated and unmyelinated axons are due to the normal developmental substitution of Na(+) channel subtype Nav 1...
September 10, 2016: Journal of Neuroscience Research
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