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https://www.readbyqxmd.com/read/29030712/calculating-the-consequences-of-left-shifted-nav-channel-activity-in-sick-excitable-cells
#1
Bela Joos, Benjamin M Barlow, Catherine E Morris
Two features common to diverse sick excitable cells are "leaky" Nav channels and bleb damage-damaged membranes. The bleb damage, we have argued, causes a channel kinetics based "leakiness." Recombinant (node of Ranvier type) Nav1.6 channels voltage-clamped in mechanically-blebbed cell-attached patches undergo a damage intensity dependent kinetic change. Specifically, they experience a coupled hyperpolarizing (left) shift of the activation and inactivation processes. The biophysical observations on Nav1.6 currents formed the basis of Nav-Coupled Left Shift (Nav-CLS) theory...
October 14, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28968364/chronic-demyelinating-polyneuropathies
#2
Jeffrey A Allen
PURPOSE OF REVIEW: This article reviews the chronic demyelinating neuropathies, with a focus on the diagnosis and treatment of immune-mediated neuropathies and the features that can help differentiate immune-mediated neuropathies from other chronic demyelinating peripheral nerve conditions. RECENT FINDINGS: Advances in clinical phenotyping and outcomes assessment have enabled neurologists to improve disease recognition, treatment, and disease monitoring. Our understanding of the immunopathogenesis of demyelinating neuropathies is evolving...
October 2017: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/28966641/reassembly-of-the-axon-initial-segment-and-nodes-of-ranvier-in-regenerated-axons-of-the-central-nervous-system
#3
Miguel A Marin, Matthew N Rasband
No abstract text is available yet for this article.
August 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28947766/neurons-define-non-myelinated-axon-segments-by-the-regulation-of-galectin-4-containing-axon-membrane-domains
#4
Natalia Díez-Revuelta, Alonso M Higuero, Silvia Velasco, María Peñas-de-la-Iglesia, Hans-Joachim Gabius, José Abad-Rodríguez
The mechanism underlying selective myelination of axons versus dendrites or neuronal somata relies on the expression of somatodendritic membrane myelination inhibitors (i.e. JAM2). However, axons still present long unmyelinated segments proposed to contribute to axonal plasticity and higher order brain functions. Why these segments remain unmyelinated is still an unresolved issue. The bifunctional lectin galectin-4 (Gal-4) organizes the transport of axon glycoproteins by binding to N-acetyllactosamine (LacNac) termini of N-glycans...
September 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923597/targeting-demyelination-via-%C3%AE-secretases-promoting-sapp%C3%AE-release-to-enhance-remyelination-in-central-nervous-system
#5
Gemma Llufriu-Dabén, Alex Carrete, Elena Chierto, Jo Mailleux, Emeline Camand, Anne Simon, Tim Vanmierlo, Christiane Rose, Bernadette Allinquant, Jerome J A Hendriks, Charbel Massaad, Delphine Meffre, Mehrnaz Jafarian-Tehrani
Remyelination is an endogenous regenerative process of myelin repair in the central nervous system (CNS) with limited efficacy in demyelinating disorders. As strategies enhancing endogenous remyelination become a therapeutic challenge, we have focused our study on α-secretase-induced sAPPα release, a soluble endogenous protein with neuroprotective and neurotrophic properties. However, the role of sAPPα in remyelination is not known. Therefore, we investigated the remyelination potential of α-secretase-induced sAPPα release following CNS demyelination in mice...
September 18, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28880874/discovery-and-mode-of-action-of-a-novel-analgesic-%C3%AE-toxin-from-the-african-spider-ceratogyrus-darlingi
#6
Silmara R Sousa, Joshua S Wingerd, Andreas Brust, Christopher Bladen, Lotten Ragnarsson, Volker Herzig, Jennifer R Deuis, Sebastien Dutertre, Irina Vetter, Gerald W Zamponi, Glenn F King, Paul F Alewood, Richard J Lewis
Spider venoms are rich sources of peptidic ion channel modulators with important therapeutical potential. We screened a panel of 60 spider venoms to find modulators of ion channels involved in pain transmission. We isolated, synthesized and pharmacologically characterized Cd1a, a novel peptide from the venom of the spider Ceratogyrus darlingi. Cd1a reversibly paralysed sheep blowflies (PD50 of 1318 pmol/g) and inhibited human Cav2.2 (IC50 2.6 μM) but not Cav1.3 or Cav3.1 (IC50 > 30 μM) in fluorimetric assays...
2017: PloS One
https://www.readbyqxmd.com/read/28827698/nogo-receptor-1-regulates-caspr-distribution-at-axo-glial-units-in-the-central-nervous-system
#7
Jae Young Lee, Min Joung Kim, Lijun Li, Alexander A Velumian, Pei Mun Aui, Michael G Fehlings, Steven Petratos
Axo-glial units are highly organised microstructures propagating saltatory conduction and are disrupted during multiple sclerosis (MS). Nogo receptor 1 (NgR1) has been suggested to govern axonal damage during the progression of disease in the MS-like mouse model, experimental autoimmune encephalomyelitis (EAE). Here we have identified that adult ngr1 (-/-) mice, previously used in EAE and spinal cord injury experiments, display elongated paranodes, and nodes of Ranvier. Unstructured paranodal regions in ngr1 (-/-) mice are matched with more distributed expression pattern of Caspr...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28806920/specific-ion-channels-contribute-to-key-elements-of-pathology-during-secondary-degeneration-following-neurotrauma
#8
Ryan L O'Hare Doig, Wissam Chiha, Marcus K Giacci, Nathanael J Yates, Carole A Bartlett, Nicole M Smith, Stuart I Hodgetts, Alan R Harvey, Melinda Fitzgerald
BACKGROUND: Following partial injury to the central nervous system, cells beyond the initial injury site undergo secondary degeneration, exacerbating loss of neurons, compact myelin and function. Changes in Ca(2+) flux are associated with metabolic and structural changes, but it is not yet clear how flux through specific ion channels contributes to the various pathologies. Here, partial optic nerve transection in adult female rats was used to model secondary degeneration. Treatment with combinations of three ion channel inhibitors was used as a tool to investigate which elements of oxidative and structural damage related to long term functional outcomes...
August 14, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28734032/characterization-of-the-axon-initial-segment-of-mice-substantia-nigra-dopaminergic-neurons
#9
Cristian González-Cabrera, Rodrigo Meza, Lorena Ulloa, Paulina Merino-Sepúlveda, Valentina Luco, Ana Sanhueza, Alejandro Oñate-Ponce, J Paul Bolam, Pablo Henny
The axon initial segment (AIS) is the site of initiation of action potentials and influences action potential waveform, firing pattern, and rate. In view of the fundamental aspects of motor function and behavior that depend on the firing of substantia nigra pars compacta (SNc) dopaminergic neurons, we identified and characterized their AIS in the mouse. Immunostaining for tyrosine hydroxylase (TH), sodium channels (Nav ) and ankyrin-G (Ank-G) was used to visualize the AIS of dopaminergic neurons. Reconstructions of sampled AIS of dopaminergic neurons revealed variable lengths (12-60 μm) and diameters (0...
July 22, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28726266/survival-among-children-with-lethal-congenital-contracture-syndrome-11-caused-by-novel-mutations-in-the-gliomedin-gene-gldn
#10
Jennifer A Wambach, Georg M Stettner, Tobias B Haack, Karin Writzl, Andreja Škofljanec, Aleš Maver, Francina Munell, Stephan Ossowski, Mattia Bosio, Daniel J Wegner, Marwan Shinawi, Dustin Baldridge, Bader Alhaddad, Tim M Strom, Dorothy K Grange, Ekkehard Wilichowski, Robin Troxell, James Collins, Barbara B Warner, Robert E Schmidt, Alan Pestronk, F Sessions Cole, Robert Steinfeld
Biallelic GLDN mutations have recently been identified among infants with lethal congenital contracture syndrome 11 (LCCS11). GLDN encodes gliomedin, a protein required for the formation of the nodes of Ranvier and development of the human peripheral nervous system. We report six infants and children from four unrelated families with biallelic GLDN mutations, four of whom survived beyond the neonatal period into infancy, childhood, and late adolescence with intensive care and chronic respiratory and nutritional support...
November 2017: Human Mutation
https://www.readbyqxmd.com/read/28720792/optical-read-out-of-neural-activity-in-mammalian-peripheral-axons-calcium-signaling-at-nodes-of-ranvier
#11
Arjun K Fontaine, Emily A Gibson, John H Caldwell, Richard F Weir
Current neural interface technologies have serious limitations for advanced prosthetic and therapeutic applications due primarily to their lack of specificity in neural communication. An optogenetic approach has the potential to provide single cell/axon resolution in a minimally invasive manner by optical interrogation of light-sensitive reporters and actuators. Given the aim of reading neural activity in the peripheral nervous system, this work has investigated an activity-dependent signaling mechanism in the peripheral nerve...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28708133/autoantibodies-in-chronic-inflammatory-neuropathies-diagnostic-and-therapeutic-implications
#12
REVIEW
Luis Querol, Jérôme Devaux, Ricard Rojas-Garcia, Isabel Illa
The chronic inflammatory neuropathies (CINs) are rare, very disabling autoimmune disorders that generally respond well to immune therapies such as intravenous immunoglobulin (IVIg). The most common forms of CIN are chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy, and polyneuropathy associated with monoclonal gammopathy of unknown significance. The field of CIN has undergone a major advance with the identification of IgG4 autoantibodies directed against paranodal proteins in patients with CIDP...
September 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28638071/emergent-stochastic-oscillations-and-signal-detection-in-tree-networks-of-excitable-elements
#13
Justus Kromer, Ali Khaledi-Nasab, Lutz Schimansky-Geier, Alexander B Neiman
We study the stochastic dynamics of strongly-coupled excitable elements on a tree network. The peripheral nodes receive independent random inputs which may induce large spiking events propagating through the branches of the tree and leading to global coherent oscillations in the network. This scenario may be relevant to action potential generation in certain sensory neurons, which possess myelinated distal dendritic tree-like arbors with excitable nodes of Ranvier at peripheral and branching nodes and exhibit noisy periodic sequences of action potentials...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615476/a-role-for-ankyring-in-maturation-and-maintenance-of-the-nodes-of-ranvier
#14
Benjamin Yang, Bridget M Curran, Stephen R Tymanskyj
No abstract text is available yet for this article.
June 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28575198/autoantibodies-to-nodal-isoforms-of-neurofascin-in-chronic-inflammatory-demyelinating-polyneuropathy
#15
Emilien Delmont, Constance Manso, Luis Querol, Andrea Cortese, Angela Berardinelli, Alessandro Lozza, Maya Belghazi, Pauline Malissart, Pierre Labauge, Guillaume Taieb, Nobuhiro Yuki, Isabel Illa, Shahram Attarian, Jérôme J Devaux
Chronic inflammatory demyelination polyneuropathy is a heterogeneous and treatable immune-mediated disorder that lacks biomarkers to support diagnosis. Recent evidence indicates that paranodal proteins (contactin 1, contactin-associated protein 1, and neurofascin-155) are the targets of autoantibodies in subsets of patients showing distinct clinical presentations. Here, we identified neurofascin-186 and neurofascin-140 as the main targets of autoantibodies in five patients presenting IgG reactivity against the nodes of Ranvier...
July 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28573768/nodes-of-ranvier-in-skin-biopsies-of-patients-with-diabetes-mellitus
#16
Kathrin Doppler, Franziska Frank, Ann-Cathrin Koschker, Karlheinz Reiners, Claudia Sommer
Paranodal demyelination has been discussed as a potential mechanism of nerve fiber damage in diabetic neuropathy (DNP). Studies on human tissue are limited, as nerve biopsies are invasive and only rarely performed in patients with confirmed DNP. Skin biopsy has recently been suggested as a tool to analyze paranodal and nodal changes of myelinated fibers. We analyzed the myelinated fibers of skin biopsies of 35 patients with DNP, 17 patients with diabetes mellitus (DM) without neuropathy, and 30 normal controls...
June 2, 2017: Journal of the Peripheral Nervous System: JPNS
https://www.readbyqxmd.com/read/28565865/alterations-of-caspr2-and-nav1-6-on-myelinated-axon-damage-in-a-rat-model-of-chronic-cerebral-hypoperfusion
#17
Weihua Liang, Weiwei Zhang, Shifu Zhao, Hua Liang, Jinli Zhang, Luyan Wang
Myelinated axons require the correct localization of key proteins that are essential for nerve conduction and cognitive function. Little is known regarding the altered expression of contactin-associated protein 2 (Caspr2) at the juxtaparanodal regions and Nav1.6 at the node of Ranvier in response to chronic cerebral hypoperfusion (CCH). The aim of the present study was to examine the alterations in the key protein of myelinated axons and the potential mechanisms that may follow CCH. We established a rat model of CCH by controllable partial narrowing of bilateral common carotid arteries...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28536506/axonal-membranes-and-their-domains-assembly-and-function-of-the-axon-initial-segment-and-node-of-ranvier
#18
REVIEW
Andrew D Nelson, Paul M Jenkins
Neurons are highly specialized cells of the nervous system that receive, process and transmit electrical signals critical for normal brain function. Here, we review the intricate organization of axonal membrane domains that facilitate rapid action potential conduction underlying communication between complex neuronal circuits. Two critical excitable domains of vertebrate axons are the axon initial segment (AIS) and the nodes of Ranvier, which are characterized by the high concentrations of voltage-gated ion channels, cell adhesion molecules and specialized cytoskeletal networks...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28534438/the-axonal-cytoskeleton-and-the-assembly-of-nodes-of-ranvier
#19
Aniket Ghosh, Diane L Sherman, Peter J Brophy
Vertebrate nervous systems rely on rapid nerve impulse transmission to support their complex functions. Fast conduction depends on ensheathment of nerve axons by myelin-forming glia and the clustering of high concentrations of voltage-gated sodium channels (Nav) in the axonal gaps between myelinated segments. These gaps are the nodes of Ranvier. Depolarization of the axonal membrane initiates the action potential responsible for impulse transmission, and the Nav help ensure that this is restricted to nodes...
May 1, 2017: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/28411148/behavioural-characterization-of-ankyring-deficient-mice-a-model-for-ank3-related-disorders
#20
I M van der Werf, D Van Dam, S Missault, B Yalcin, P P De Deyn, G Vandeweyer, R F Kooy
ANK3 encodes AnkyrinG (AnkG), a member of the Ankyrin family that is expressed in several different isoforms in many tissues. A unique serine-rich domain and tail domain in the two largest isoforms of AnkG (270 and 480kDa), restrict AnkG to the axon initial segment and nodes of Ranvier of myelinated neurons. At these sites, AnkG is a master regulator, coordinating the strict clustering of components necessary for proper action potential initiation and propagation along the axon. These components include voltage-gated sodium channels, potassium channels and members of the L1 cell adhesion molecule family...
April 11, 2017: Behavioural Brain Research
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