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 ◽  
...  
2000 ◽  
Vol 150 (3) ◽  
pp. 657-666 ◽  
Author(s):  
Steven Tait ◽  
Frank Gunn-Moore ◽  
J. Martin Collinson ◽  
Jeffery Huang ◽  
Catherine Lubetzki ◽  
...  

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.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lars B. Dahlin ◽  
Kristian R. Rix ◽  
Vedrana A. Dahl ◽  
Anders B. Dahl ◽  
Janus N. Jensen ◽  
...  

AbstractA deeper knowledge of the architecture of the peripheral nerve with three-dimensional (3D) imaging of the nerve tissue at the sub-cellular scale may contribute to unravel the pathophysiology of neuropathy. Here we demonstrate the feasibility of X-ray phase contrast holographic nanotomography to enable 3D imaging of nerves at high resolution, while covering a relatively large tissue volume. We show various subcomponents of human peripheral nerves in biopsies from patients with type 1 and 2 diabetes and in a healthy subject. Together with well-organized, parallel myelinated nerve fibres we show regenerative clusters with twisted nerve fibres, a sprouted axon from a node of Ranvier and other specific details. A novel 3D construction (with movie created) of a node of Ranvier with end segment of a degenerated axon and sprout of a regenerated one is captured. Many of these architectural elements are not described in the literature. Thus, X-ray phase contrast holographic nanotomography enables identifying specific morphological structures in 3D in peripheral nerve biopsies from a healthy subject and from patients with type 1 and 2 diabetes.


At a node of Ranvier the axon is reduced in diameter; on the largest mammalian fibres the reduction is to less than half of the internodal diameter. The axoplasm at the node has optical properties different from the internodal axoplasm, but there is no visible transverse boundary across it. The length of the portion of axon left uncovered at the node is less than 0·5 μ in the largest mammalian fibres; it is somewhat greater on the smaller fibres. The area of the cylinder of axon membrane exposed at the node increases only slightly with increasing fibre diameter. This area is 4 μ 2 , and the area of the surface of the narrow portion of the axon is about 90 μ 2 , in the largest mammalian fibres. The exposed portion of the axon is probably not covered by Schwann cell protoplasm, but is surrounded by a 'cementing disk’ composed of scleroprotein material, continuous with the neurilemma (inner endoneurium). This disk has a radial thickness of 5 μ in the largest mammalian fibres. Outside this disk is a perinodal space with no stainable contents, bounded externally by the collagenous outer endoneurium (sheath of Key & Retzius). Methylene blue and silver nitrate entering the fibres at the node stain the whole narrow region, suggesting that this, rather than the myelin-free area, may constitute the effective nodal membrane. Periodic interruptions of the myelin occur along fibres of the spinal cord of rabbits, probably on all fibres. On central fibres of 3 to 15 μ in diameter the internodal lengths vary from 300 to 1700 μ . As in peripheral nerves internodal length increases with growth; in smaller rabbits this length is less for any given fibre diameter than in larger animals. In new -born rabbits the smallest fibres have internodes as short as 200 μ .


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Elise LV Malavasi ◽  
Aniket Ghosh ◽  
Daniel G Booth ◽  
Michele Zagnoni ◽  
Diane L Sherman ◽  
...  

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.


2021 ◽  
pp. 135245852110281
Author(s):  
Xiaodan Hou ◽  
Yan Liang ◽  
Pan Cui ◽  
Junwei Hao

Background: Combined central and peripheral demyelination (CCPD) is a disease of inflammatory demyelination that affects central and peripheral nerves simultaneously or temporally separated. Objectives: This study evaluated the clinical characteristics and the existence of antinodal/paranodal antibodies in patients with CCPD. Methods: We reviewed the clinical manifestations, laboratory tests, electrophysiological examinations, neuroimaging findings, treatment, and prognosis of 31 patients with CCPD. Using a live cell–based assay, we tested antinodal/paranodal antibodies. Results: The most common symptoms were motor weakness (83.3%), hyporeflexia (63.3%), and sphincter disturbance (58.1%). In total, 16.6% of patients had impaired vision symptoms, whereas 33.3% of patients had abnormal visual-evoked potentials (VEPs). A total of 21.1% (4/19) of patients were positive for anti-AQP4 (aquaporin 4) antibodies, 20.0% (2/10) of patients were positive for anti-NF155 (neurofascin-155) antibodies, and 10.0% (1/10) of patients were positive for anti-MAG (myelin-associated glycoprotein) antibodies. The effective rates of intravenous corticosteroids, intravenous immunoglobulins, and rituximab were 72.2%, 37.5%, and 100%, respectively. At the illness peak, 75% of patients with CCPD had an mRS (modified Rankin Scale) score of 4 or greater. In remission, 37.5% had an mRS score of 4 or greater. Conclusion: The clinical manifestations of patients with CCPD are highly heterogeneous. We recommend testing antinodal/paranodal antibodies for patients with CCPD.


Author(s):  
D. M. DePace

The majority of blood vessels in the superior cervical ganglion possess a continuous endothelium with tight junctions. These same features have been associated with the blood brain barrier of the central nervous system and peripheral nerves. These vessels may perform a barrier function between the capillary circulation and the superior cervical ganglion. The permeability of the blood vessels in the superior cervical ganglion of the rat was tested by intravenous injection of horseradish peroxidase (HRP). Three experimental groups of four animals each were given intravenous HRP (Sigma Type II) in a dosage of.08 to.15 mg/gm body weight in.5 ml of.85% saline. The animals were sacrificed at five, ten or 15 minutes following administration of the tracer. Superior cervical ganglia were quickly removed and fixed by immersion in 2.5% glutaraldehyde in Sorenson's.1M phosphate buffer, pH 7.4. Three control animals received,5ml of saline without HRP. These were sacrificed on the same time schedule. Tissues from experimental and control animals were reacted for peroxidase activity and then processed for routine transmission electron microscopy.


Author(s):  
D. A. Fischman ◽  
J. E. Dennis ◽  
T. Obinata ◽  
H. Takano-Ohmuro

C-protein is a 150 kDa protein found within the A bands of all vertebrate cross-striated muscles. By immunoelectron microscopy, it has been demonstrated that C-protein is distributed along a series of 7-9 transverse stripes in the medial, cross-bridge bearing zone of each A band. This zone is now termed the C-zone of the sarcomere. Interest in this protein has been sparked by its striking distribution in the sarcomere: the transverse repeat between C-protein stripes is 43 nm, almost exactly 3 times the 14.3 nm axial repeat of myosin cross-bridges along the thick filaments. The precise packing of C-protein in the thick filament is still unknown. It is the only sarcomeric protein which binds to both myosin and actin, and the actin-binding is Ca-sensitive. In cardiac and slow, but not fast, skeletal muscles C-protein is phosphorylated. Amino acid composition suggests a protein of little or no αhelical content. Variant forms (isoforms) of C-protein have been identified in cardiac, slow and embryonic muscles.


Author(s):  
Bruce R. Pachter

Diabetes mellitus is one of the commonest causes of neuropathy. Diabetic neuropathy is a heterogeneous group of neuropathic disorders to which patients with diabetes mellitus are susceptible; more than one kind of neuropathy can frequently occur in the same individual. Abnormalities are also known to occur in nearly every anatomic subdivision of the eye in diabetic patients. Oculomotor palsy appears to be common in diabetes mellitus for their occurrence in isolation to suggest diabetes. Nerves to the external ocular muscles are most commonly affected, particularly the oculomotor or third cranial nerve. The third nerve palsy of diabetes is characteristic, being of sudden onset, accompanied by orbital and retro-orbital pain, often associated with complete involvement of the external ocular muscles innervated by the nerve. While the human and experimental animal literature is replete with studies on the peripheral nerves in diabetes mellitus, there is but a paucity of reported studies dealing with the oculomotor nerves and their associated extraocular muscles (EOMs).


Author(s):  
John L. Beggs ◽  
Peter C. Johnson ◽  
Astrid G. Olafsen ◽  
C. Jane Watkins

The blood supply (vasa nervorum) to peripheral nerves is composed of an interconnected dual circulation. The endoneurium of nerve fascicles is maintained by the intrinsic circulation which is composed of microvessels primarily of capillary caliber. Transperineurial arterioles link the intrinsic circulation with the extrinsic arterial supply located in the epineurium. Blood flow in the vasa nervorum is neurogenically influenced (1,2). Although a recent hypothesis proposes that endoneurial blood flow is controlled by the action of autonomic nerve fibers associated with epineurial arterioles (2), our recent studies (3) show that in addition to epineurial arterioles other segments of the vasa nervorum are also innervated. In this study, we examine blood vessels of the endoneurium for possible innervation.


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