scholarly journals Dynamic early clusters of nodal proteins contribute to node of Ranvier assembly during myelination of peripheral neurons

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Elise LV Malavasi ◽  
Aniket Ghosh ◽  
Daniel G Booth ◽  
Michele Zagnoni ◽  
Diane L Sherman ◽  
...  
Keyword(s):  
Peripheral Nerves ◽  
Lateral Diffusion ◽  
Nerve Impulse ◽  
Node Of Ranvier ◽  
Axonal Membrane ◽  
Macromolecular Complexes ◽  
Peripheral Neurons ◽  
Voltage Gated Sodium Channels ◽  
Peripheral Node ◽  
Nerve Impulse Conduction

Voltage-gated sodium channels cluster in macromolecular complexes at nodes of Ranvier to promote rapid nerve impulse conduction in vertebrate nerves. Node assembly in peripheral nerves is thought to be initiated at heminodes at the extremities of myelinating Schwann cells and fusion of heminodes results in the establishment of nodes. Here we show that assembly of 'early clusters' of nodal proteins in the murine axonal membrane precedes heminode formation. The Neurofascin (Nfasc) proteins are essential for node assembly, and the formation of early clusters also requires neuronal Nfasc. Early clusters are mobile and their proteins are dynamically recruited by lateral diffusion. They can undergo fusion not only with each other but also with heminodes thus contributing to the development of nodes in peripheral axons. The formation of early clusters constitutes the earliest stage in peripheral node assembly and expands the repertoire of strategies that have evolved to establish these essential structures.

Carboxytherapy in the practice of an occupational pathologist: experience of use in cervical dorsopathy in workers of harmful professions

2020 ◽  
pp. 8-18
Author(s):  
Shaykhlislamova Elmira Radikovna ◽  
Urmantseva Ferdaus Anvarovna ◽  
Gallyamova Svetlana Anifovna ◽  
Valeeva Elvira Timeryanovna
Keyword(s):  
Carbon Dioxide ◽  
Peripheral Nerves ◽  
Nerve Impulse ◽  
Pain Syndrome ◽  
Upper Extremities ◽  
Negative Consequences ◽  
Basic Drug ◽  
Physiological Properties ◽  
Myofascial Syndrome ◽  
Nerve Impulse Conduction

The task of ensuring the working capacity of the country’s industrial potential is to preserve the health of employees of enterprises with harmful working conditions. High rates of general morbidity and disability of the working population due to vertebrogenic diseases of the spine, the genesis of which is associated with organ overstrain, microtraumatization and vibration exposure, make the problem of treatment, prevention and rehabilitation of this pathology a priority in occupational medicine. In the present study, the expediency of using carboxytherapy in the treatment of cervical dorsopathies in 2 groups of patients working in harmful professions has been studied, in one of which, along with basic drug treatment, physiotherapy exercises and massage, injections of purified carbon dioxide into paravertebral points are included in the complex of therapy. At the end of the course of treatment in the group of patients receiving carboxytherapy, a more significant improvement in clinical and electrophysiological parameters was achieved: a decrease in the intensity of pain syndrome according to a visual analogue scale by 73.3 %, myofascial syndrome by 33.3 %, expansion of the range of motion by 40 %; according to stimulation electroneuromyography and rheovasography — improvement of nerve impulse conduction along the peripheral nerves of the upper extremities and the roots of the C6–8 — Th1 spinal nerves by 35 %, the hemodynamics of peripheral blood vessels of the upper extremities by 45 %. The extensive physiological properties of carbon dioxide, the availability and safety of the method, the absence of negative consequences, the effectiveness shown in the study allows us to recommend the use of carboxytherapy in occupational pathological practice in the treatment of vertebrogenic reflex syndromes in workers in hazardous occupations.

scholarly journals The Axonal Cytoskeleton and the Assembly of Nodes of Ranvier

2017 ◽  
Vol 24 (2) ◽  
pp. 104-110 ◽  
Author(s):  
Aniket Ghosh ◽  
Diane L. Sherman ◽  
Peter J. Brophy
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Protein Complexes ◽  
Nerve Impulse ◽  
Nodes Of Ranvier ◽  
Axonal Membrane ◽  
Voltage Gated Sodium Channels ◽  
The Central Nervous System ◽  
High Concentrations ◽  
Surface Domains

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. In the central nervous system, the formation of nodes and the clustering of Nav in nodal complexes is achieved when oligodendrocytes extend their processes and ultimately ensheath axons with myelin. However, the mechanistic relationship between myelination and the formation of nodal complexes is unclear. Here we review recent work in the central nervous system that shows that axons, by assembling distinct cytoskeletal interfaces, are not only active participants in oligodendrocyte process migration but are also significant contributors to the mechanisms by which myelination causes Nav clustering. We also discuss how the segregation of membrane protein complexes through their interaction with distinct cytoskeletal complexes may play a wider role in establishing surface domains in axons.

scholarly journals Electron tomographic analysis of cytoskeletal cross-bridges in the paranodal region of the node of Ranvier in peripheral nerves

2008 ◽  
Vol 161 (3) ◽  
pp. 469-480 ◽  
Author(s):  
Guy A. Perkins ◽  
Gina E. Sosinsky ◽  
Sassan Ghassemzadeh ◽  
Alex Perez ◽  
Ying Jones ◽  
...  
Keyword(s):  
Peripheral Nerves ◽  
Node Of Ranvier ◽  
Cross Bridges ◽  
Tomographic Analysis

scholarly journals Clinical lecture on the pre-certification cycle of doctors on the specialty "General practice-family medicine" on the subject "Mononeuropathy (Neuritis and Neuralgia) and Plexopathy (Plexitis and Plexaglia): etiology, pathogenesis, clinic, diagnostics, t

2017 ◽  
pp. 25-29
Author(s):  
V. Sereda ◽  
N. Svyrydova ◽  
I. Dovgiy
Keyword(s):  
General Practice ◽  
Family Medicine ◽  
Peripheral Nerves ◽  
Metabolic Disorders ◽  
Nerve Impulse ◽  
Nerve Fibers ◽  
Motor Functions ◽  
The Subject ◽  
Clinical Lecture

Neuralgia and neuritis (plexitis) are lesions of the peripheral nerves caused by hypothermia, infection, trauma, intoxication, and metabolic disorders. Neuralgia is characterized by pain arising along the course of a nerve or its branches. Neuritis is accompanied by sensitivity disorders, trophic disorders, paresis and paralysis, as well as those that perceive the nerve impulse (sensitivity) and motor functions. All this is associated with varying degrees of degeneration of nerve fibers until their breakdown.

scholarly journals ATP Release through Lysosomal Exocytosis from Peripheral Nerves: The Effect of Lysosomal Exocytosis on Peripheral Nerve Degeneration and Regeneration after Nerve Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Junyang Jung ◽  
Hyun Woo Jo ◽  
Hyunseob Kwon ◽  
Na Young Jeong
Keyword(s):  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Peripheral Nerves ◽  
Wallerian Degeneration ◽  
Atp Release ◽  
Nerve Degeneration ◽  
Peripheral Neurons ◽  
Charcot Marie Tooth Disease ◽  
Axonal Degradation

Studies have shown that lysosomal activation increases in Schwann cells after nerve injury. Lysosomal activation is thought to promote the engulfment of myelin debris or fragments of injured axons in Schwann cells during Wallerian degeneration. However, a recent interpretation of lysosomal activation proposes a different view of the phenomenon. During Wallerian degeneration, lysosomes become secretory vesicles and are activated for lysosomal exocytosis. The lysosomal exocytosis triggers adenosine 5′-triphosphate (ATP) release from peripheral neurons and Schwann cells during Wallerian degeneration. Exocytosis is involved in demyelination and axonal degradation, which facilitate nerve regeneration following nerve degeneration. At this time, released ATP may affect the communication between cells in peripheral nerves. In this review, our description of the relationship between lysosomal exocytosis and Wallerian degeneration has implications for the understanding of peripheral nerve degenerative diseases and peripheral neuropathies, such as Charcot-Marie-Tooth disease or Guillain-Barré syndrome.

Spectral Investigations, Molecular Interactions and Electrochemical Studies of (2R)-(-)2-(2, 6-dimethylphenylaminocarbonyl)-1-methyl Piperidinium Chloride

2020 ◽  
Vol 15 (4) ◽  
pp. 358-368
Author(s):  
J. Deva Anban ◽  
J. Sharmi Kumar ◽  
C. James ◽  
Sayantan Pradhan
Keyword(s):  
Sodium Channels ◽  
Local Anesthetics ◽  
Natural Bond Orbital ◽  
Nbo Analysis ◽  
Basis Set ◽  
Voltage Gated ◽  
Peripheral Neurons ◽  
Voltage Gated Sodium Channels ◽  
Title Molecule ◽  
Inner Pore

Background: Local anesthetics are widely used to decrease sensitivity to pain in specific regions of the body while performing medical tasks. Many studies have probed the mechanism of action of local anesthetics but still many questions remain. (2R - (-) 2 - (2, 6-dimethylphenylaminocarbonyl) - 1 – methyl piperidinium chloride (DAMP), is an extensively used amide-type local anesthetic. Objective: This study aims at revealing the various electrophysical and chemical properties of the title compound. This study will be useful for future research by pharmacologists. Method: Density Functional Theory (DFT) computations were executed using Gaussian’09 program package and were optimized with the B3LYP /6-311+G (d, p) basis set. Natural bond orbital (NBO) analysis was carried out with version 3.1. Normal Coordinate Analysis (NCA) was used to systematically calculate the harmonic vibrational wavenumbers. Molecular docking simulations were carried out to understand the pharmacokinetic behavior of the drug. Results: The presence of strong N-H…Cl intra molecular hydrogen bonding was evidently revealed from the FT-IR spectrum due to the shifting of NH stretching wavenumber. Stability of the molecule arising from hyper conjugative interactions exhibits the bioactivity of the molecule by natural bond orbital analysis. The title molecule binds to the inner pore and blocks voltage - gated sodium channels in peripheral neurons. Conclusion: A detailed molecular picture of DAMP and its interactions were obtained by modeling analysis, IR, Raman, and UV-Vis spectroscopy. The geometrical parameters agree well with the XRD data. NBO analysis indicates the bioactivity of the molecule. The HOMO-LUMO energy gap indicates the possibility of intramolecular charge transfer of the molecule. From the ligand docking studies it is concluded that the title molecule binds to the inner pore and blocks voltage - gated sodium channels in peripheral neurons.

scholarly journals Axons provide the secretory machinery for trafficking of voltage-gated sodium channels in peripheral nerve

2016 ◽  
Vol 113 (7) ◽  
pp. 1823-1828 ◽  
Author(s):  
Carolina González ◽  
José Cánovas ◽  
Javiera Fresno ◽  
Eduardo Couve ◽  
Felipe A. Court ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Sodium Channel ◽  
Sodium Channels ◽  
Neural Function ◽  
Axonal Membrane ◽  
Local Synthesis ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

The regulation of the axonal proteome is key to generate and maintain neural function. Fast and slow axoplasmic waves have been known for decades, but alternative mechanisms to control the abundance of axonal proteins based on local synthesis have also been identified. The presence of the endoplasmic reticulum has been documented in peripheral axons, but it is still unknown whether this localized organelle participates in the delivery of axonal membrane proteins. Voltage-gated sodium channels are responsible for action potentials and are mostly concentrated in the axon initial segment and nodes of Ranvier. Despite their fundamental role, little is known about the intracellular trafficking mechanisms that govern their availability in mature axons. Here we describe the secretory machinery in axons and its contribution to plasma membrane delivery of sodium channels. The distribution of axonal secretory components was evaluated in axons of the sciatic nerve and in spinal nerve axons after in vivo electroporation. Intracellular protein trafficking was pharmacologically blocked in vivo and in vitro. Axonal voltage-gated sodium channel mRNA and local trafficking were examined by RT-PCR and a retention-release methodology. We demonstrate that mature axons contain components of the endoplasmic reticulum and other biosynthetic organelles. Axonal organelles and sodium channel localization are sensitive to local blockade of the endoplasmic reticulum to Golgi transport. More importantly, secretory organelles are capable of delivering sodium channels to the plasma membrane in isolated axons, demonstrating an intrinsic capacity of the axonal biosynthetic route in regulating the axonal proteome in mammalian axons.

scholarly journals An Oligodendrocyte Cell Adhesion Molecule at the Site of Assembly of the Paranodal Axo-Glial Junction

2000 ◽  
Vol 150 (3) ◽  
pp. 657-666 ◽  
Author(s):  
Steven Tait ◽  
Frank Gunn-Moore ◽  
J. Martin Collinson ◽  
Jeffery Huang ◽  
Catherine Lubetzki ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Peripheral Nerves ◽  
Cell Adhesion Molecule ◽  
Close Association ◽  
Node Of Ranvier ◽  
Septate Junction ◽  
Adhesion Zone ◽  
Paranodal Junctions ◽  
The Central Nervous System

Two major isoforms of the cell adhesion molecule neurofascin NF186 and NF155 are expressed in the central nervous system (CNS). We have investigated their roles in the assembly of the node of Ranvier and show that they are targeted to distinct domains at the node. At the onset of myelination, NF186 is restricted to neurons, whereas NF155 localizes to oligodendrocytes, the myelin-forming glia of the CNS. Coincident with axon ensheathment, NF155 clusters at the paranodal regions of the myelin sheath where it localizes in apposition to the axonal adhesion molecule paranodin/contactin-associated protein (Caspr1), which is a constituent of the septate junction-like axo-glial adhesion zone. Immunoelectron microscopy confirmed that neurofascin is a glial component of the paranodal axo-glial junction. Concentration of NF155 with Caspr1 at the paranodal junctions of peripheral nerves is also a feature of Schwann cells. In Shiverer mutant mice, which assemble neither compact CNS myelin nor normal paranodes, NF155 (though largely retained at the cell body) is also distributed at ectopic sites along axons, where it colocalizes with Caspr1. Hence, NF155 is the first glial cell adhesion molecule to be identified in the paranodal axo-glial junction, where it likely interacts with axonal proteins in close association with Caspr1.

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