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Nodes of ranvier

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
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...
2016: Nature Communications
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
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
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
Miguel A Marin, Silmara de Lima, Hui-Ya Gilbert, Roman J Giger, Larry Benowitz, Matthew N Rasband
UNLABELLED: Action potential initiation and propagation in myelinated axons require ion channel clustering at axon initial segments (AIS) and nodes of Ranvier. Disruption of these domains after injury impairs nervous system function. Traditionally, injured CNS axons are considered refractory to regeneration, but some recent approaches challenge this view by showing robust long-distance regeneration. However, whether these approaches allow remyelination and promote the reestablishment of AIS and nodes of Ranvier is unknown...
August 31, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Nargess Gandomi, Reyhaneh Varshochian, Fatemeh Atyabi, Mohammad Hossein Ghahremani, Mohammad Sharifzadeh, Mohsen Amini, Rassoul Dinarvand
Multiple sclerosis (MS) is a chronic central nervous system (CNS) inflammation. Efficient drug delivery to brain is however hampered by blood brain barrier (BBB). In order to have highly efficient and safe delivery of drugs to brain, solid lipid nanoparticles (SLNs) have indicated promising potentials as smart carriers that can pass the blood brain barrier and deliver therapeutic biomolecules to the brain. In this study pegylated SLNs surface modified with using anti-Contactin2 or anti-Neurofascin, two axo-glial-glycoprotein antigens located in node of Ranvier, were prepared...
August 30, 2016: Pharmaceutical Development and Technology
Werner Badenhorst, Tania Hanekom, Johan J Hanekom
This study presents the development of an alternative noise current term and novel voltage-dependent current noise algorithm for conductance-based stochastic auditory nerve fibre (ANF) models. ANFs are known to have significant variance in threshold stimulus which affects temporal characteristics such as latency. This variance is primarily caused by the stochastic behaviour or microscopic fluctuations of the node of Ranvier's voltage-dependent sodium channels of which the intensity is a function of membrane voltage...
August 25, 2016: Biological Cybernetics
Ibrahima Dione, Jean Deteix, Thomas Briffard, Eric Chamberland, Nicolas Doyon
In neural structures with complex geometries, numerical resolution of the Poisson-Nernst-Planck (PNP) equations is necessary to accurately model electrodiffusion. This formalism allows one to describe ionic concentrations and the electric field (even away from the membrane) with arbitrary spatial and temporal resolution which is impossible to achieve with models relying on cable theory. However, solving the PNP equations on complex geometries involves handling intricate numerical difficulties related either to the spatial discretization, temporal discretization or the resolution of the linearized systems, often requiring large computational resources which have limited the use of this approach...
2016: PloS One
Joseph Lombardo, Melissa A Harrington
KCNQ/Kv7 channels form a slow non-inactivating K(+) current, also known as the M-current. They activate in the sub-threshold range of membrane potentials and regulate different aspects of excitability in neurons of the central nervous system. In spinal motoneurons (MNs), KCNQ/Kv7 channels have been identified in the somata, axonal initial segment (AIS) and nodes of Ranvier where they generate a slow, non-inactivating, K+ current sensitive to both muscarinic receptor-mediated inhibition and KCNQ/Kv7 channel blockers...
August 10, 2016: Journal of Neurophysiology
Sage Begolly, Peter G Shrager, John A Olschowka, Jacqueline P Williams, M Kerry O'Banion
PURPOSE: To determine the late effects of fractionated versus single-dose cranial radiation on murine white matter. METHODS AND MATERIALS: Mice were exposed to 0 Gy, 6 × 6 Gy, or 1 × 20 Gy cranial irradiation at 10 to 12 weeks of age. Endpoints were assessed through 18 months from exposure using immunohistochemistry, electron microscopy, and electrophysiology. RESULTS: Weight gain was temporarily reduced after irradiation; greater loss was seen after single versus fractionated doses...
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Yoshinori Otani, Leonid M Yermakov, Jeffrey L Dupree, Keiichiro Susuki
INTRODUCTION: Peripheral nerves are often exposed to mechanical stress leading to compression neuropathies. The pathophysiology underlying nerve dysfunction by chronic compression is largely unknown. METHODS: We analyzed molecular organization and fine structures at and near nodes of Ranvier in a compression neuropathy model in which a silastic tube was placed around the mouse sciatic nerve. RESULTS: Immunofluorescence study showed that clusters of cell adhesion complex forming paranodal axoglial junctions were dispersed with frequent overlap with juxtaparanodal components...
July 27, 2016: Muscle & Nerve
Lemont B Kier
Our previous studies of the role of proton hopping in nerve conduction have dealt with the axon, soma, synapse, and nodes of Ranvier. We complete the study and application of the theory of proton hopping being the system of nerve conduction by examining the dendrites and their accompanying spines as they function within the nerve system. The role of proton hopping continues to be a very probable mechanism within this intermediate system linking two nerves at the synapse.
July 25, 2016: Current Computer-aided Drug Design
David R Serwanski, Peter Jukkola, Akiko Nishiyama
The node of Ranvier is a functionally important site on the myelinated axon where sodium channels are clustered and regeneration of action potentials occurs, allowing fast saltatory conduction of action potentials. Early ultrastructural studies have revealed the presence of "glia" or "astrocytes" at the nodes. NG2 cells, also known as oligodendrocyte precursor cells or polydendrocytes, which are a resident glial cell population in the mature mammalian central nervous system that is distinct from astrocytes, have also been shown to extend processes that contact the nodes...
July 22, 2016: Journal of Comparative Neurology
Yiyu Deng, Qianpeng Han, Fengcai Shen, Mengmeng Chen, Hongke Zeng
OBJECTIVE: To observe the axonal development in the corpus callosum of septic neonatal rats, and its effect on the neurological function after birth. METHODS: Forty-eight 1-day-old Sprague-Dawley (SD) rats were randomly divided into two groups: control group and sepsis group, with 24 rats in each group. The rat model of sepsis was reproduced by intraperitoneal injection of 1 mg/kg lipopolysaccharide (LPS), and the rats in control group were injected with an equal volume of phosphate buffered saline (PBS)...
August 2016: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Vivien Parker, Jodi Warman Chardon, Julie Mills, Claire Goldsmith, Pierre R Bourque
Objective. The ability to correctly identify chronic demyelinating neuropathy can have important therapeutic and prognostic significance. The stimulus intensity value required to obtain a supramaximal compound muscle action potential amplitude is a commonly acquired data point that has not been formally assessed as a diagnostic tool in routine nerve conduction studies to identify chronic neuropathies. We postulated that this value was significantly elevated in chronic demyelinating neuropathy. Methods. We retrospectively reviewed electrophysiology laboratory records to compare the stimulus intensity values recorded during median and ulnar motor nerve conduction studies...
2016: Neuroscience Journal
Josune García-Sanmartín, Susana Rubio-Mediavilla, José J Sola-Gallego, Alfredo Martínez
Schwann cells generate myelin sheaths around the axons of the peripheral nervous system, thus facilitating efficient nerve impulse propagation. Two main tumor types can arise from peripheral nerves, schwannomas and neurofibromas, which are sometimes difficult to distinguish and may require the use of diagnostic biomarkers. Here, we characterize a new marker for Schwann cells and its potential use as a diagnostic marker for schwannomas. Immunohistochemistry for Glu-tubulin, a posttranslational modification of α-tubulin, was performed in mouse and human tissues...
October 2016: Histochemistry and Cell Biology
Larisa C Kruger, Heather A O'Malley, Jacob M Hull, Amanda Kleeman, Gustavo A Patino, Lori L Isom
UNLABELLED: Voltage-gated sodium channel (VGSC) β subunits signal through multiple pathways on multiple time scales. In addition to modulating sodium and potassium currents, β subunits play nonconducting roles as cell adhesion molecules, which allow them to function in cell-cell communication, neuronal migration, neurite outgrowth, neuronal pathfinding, and axonal fasciculation. Mutations in SCN1B, encoding VGSC β1 and β1B, are associated with epilepsy. Autosomal-dominant SCN1B-C121W, the first epilepsy-associated VGSC mutation identified, results in genetic epilepsy with febrile seizures plus (GEFS+)...
June 8, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Yoshiko Takagishi, Kimiaki Katanosaka, Hiroyuki Mizoguchi, Yoshiharu Murata
Emerging evidence suggests that axonal degeneration is a disease mechanism in various neurodegenerative diseases and that the paranodes at the nodes of Ranvier may be the initial site of pathogenesis. We investigated the pathophysiology of the disease process in the central and peripheral nervous systems of a Caspr mutant mouse, shambling (shm), which is affected by disrupted paranodal structures and impaired nerve conduction of myelinated nerves. The shm mice manifest a progressive neurological phenotype as mice age...
July 2016: Neurobiology of Aging
Chuansheng Zhang, Matthew N Rasband
Neurons are organized and connected into functional circuits by axons that conduct action potentials. Many vertebrate axons are myelinated and further subdivided into excitable domains that include the axon initial segment (AIS) and nodes of Ranvier. Nodes of Ranvier regenerate and propagate action potentials, while AIS regulate action potential initiation and neuronal polarity. Two distinct cytoskeletons control axon structure and function: 1) a submembranous ankyrin/spectrin cytoskeleton that clusters ion channels and provides mechanical support, and 2) a microtubule-based cytoskeleton that controls selective trafficking of dendritic and axonal cargoes...
August 2016: Current Opinion in Neurobiology
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