Preferential localization of prostamide/prostaglandin F synthase in myelin sheaths of the central nervous system

The integrity of myelin sheaths is maintained by oligodendrocytes and Schwann cells respectively in the central nervous system (CNS) and in the peripheral nervous system. The process of demyelination consisting of the withdrawal of myelin sheaths from their axons is a characteristic feature of multiple sclerosis, the most common human demyelinating disease. Many experimental models have been designed to study the biology of demyelination and remyelination (repair of the lost myelin) in the CNS, due to the difficulties in studying human material. In the ethidium bromide (an intercalating gliotoxic drug) model of demyelination, CNS remyelination may be carried out by surviving oligodendrocytes and/or by cells differentiated from the primitive cell lines or either by Schwann cells that invade the CNS. However, some factors such as the age of the experimental animals, intensity and time of exposure to the intercalating chemical and the topography of the lesions have marked influence on the repair of the tissue.

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A STRUCTURAL ANALYSIS OF THE MYELIN SHEATH IN THE CENTRAL NERVOUS SYSTEM

The Journal of Cell Biology ◽

10.1083/jcb.34.2.555 ◽

1967 ◽

Vol 34 (2) ◽

pp. 555-567 ◽

Cited By ~ 131

Author(s):

Asao Hirano ◽

Herbert M. Dembitzer

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Electron Microscope ◽

Myelin Sheath ◽

Cerebral White Matter ◽

Experimental Conditions ◽

Myelin Sheaths ◽

Basic Theme ◽

Cell Processes ◽

The Central Nervous System

The cerebral white matter of rats subjected to a variety of noxious experimental conditions was examined in the electron microscope. Several unusual configurations of the myelin sheath are identified in addition to the usual configuration. These variations include the presence of (a) formed organelles within the inner and outer loops, (b) isolated islands of cytoplasm in unfused portions of the major dense lines, (c) apparently unconnected cell processes between the sheath and the axon, and (d) concentric, double myelin sheaths. A generalized model of the myelin sheath based on a hypothetical unrolling of the sheath is described. It consists of a shovel-shaped myelin sheet surrounded by a continuous thickened rim of cytoplasm. Most of the unusual myelin configurations are explained as simple variations on this basic theme. With the help of this model, an explanation of the formation of the myelin sheath is offered. This explanation involves the concept that myelin formation can occur at all cytoplasmic areas adjacent to the myelin proper and that adjacent myelin lamellae can move in relation to each other.

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Observations on the Chemical Composition of Myelin and the Smallest Size of Myelinated Nerve-Fibres in the Central Nervous System

Journal of Cell Science ◽

10.1242/jcs.s3-89.5.89 ◽

1948 ◽

Vol s3-89 (5) ◽

pp. 89-102

Author(s):

A. BRODAL ◽

R. G. HARRISON

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Chemical Composition ◽

Nile Blue ◽

Nerve Fibres ◽

Myelinated Nerve ◽

Myelin Sheaths ◽

The Central Nervous System

Baker's (1946) acid haematein and pyridine-extraction control tests, claimed to be specific for phospholipines (Baker, 1947), have been applied to various parts of the central nervous system of rats and man. The sudan black method for the detection of lipoids and the nile blue method for the staining of acidic lipoids have also been used. The findings are in agreement with older statements in the literature that myelin contains a considerable amount of phospholipines. It was impossible to determine whether galactolipines or neutral lipoids are also present. In the acid haematein-stained sections finer fibres were seen than when other stains for myelin sheaths are employed. Fibres with a diameter of 0.5 µ or even somewhat less were stained in various parts of the central nervous system of rats. It is regarded as probable from these findings that fibres down to 0.5 µ or even smaller possess a lipoid investment. These observations lend support to the now commonly accepted view that the distinction between myelinated and so-called unmyelinated fibres is arbitrary. Some observations are made, however, which indicate that the presence of truly unmyelinated fibres cannot be excluded.

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THE FORMATION AND STRUCTURE OF MYELIN SHEATHS IN THE CENTRAL NERVOUS SYSTEM

The Journal of Cell Biology ◽

10.1083/jcb.8.2.431 ◽

1960 ◽

Vol 8 (2) ◽

pp. 431-446 ◽

Cited By ~ 124

Author(s):

A. Peters

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Electron Microscope ◽

Xenopus Laevis ◽

Peripheral Nervous System ◽

Nerve Fibre ◽

Potassium Permanganate ◽

Myelin Sheaths ◽

A Cell ◽

The Central Nervous System

The development and structure of myelin sheaths have been studied in the optic nerves of rats and of Xenopus laevis tadpoles. Both potassium permanganate- and osmium-fixed material was examined with the electron microscope. In the first stage of myelinogenesis the nerve fibre is surrounded by a cell process which envelops it and forms a mesaxon. The mesaxon then elongates into a loose spiral from which the cytoplasm is later excluded, so that compact myelin is formed. This process is similar to myelinogenesis in the peripheral nervous system, although in central fibres the cytoplasm on the outside of the myelin is confined in a tongue-like process to a fraction of the circumference, leaving the remainder of the sheath uncovered, so that contacts are possible between adjacent myelin sheaths. The structure of nodes in the central nervous system has been described and it is suggested that the oligodendrocytes may be the myelin-forming cells.

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FURTHER OBSERVATIONS ON THE STRUCTURE OF MYELIN SHEATHS IN THE CENTRAL NERVOUS SYSTEM

The Journal of Cell Biology ◽

10.1083/jcb.20.2.281 ◽

1964 ◽

Vol 20 (2) ◽

pp. 281-296 ◽

Cited By ~ 79

Author(s):

A. Peters

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Direct Evidence ◽

Radial Component ◽

Adult Rats ◽

Direction Parallel ◽

Myelin Sheaths ◽

Adult Mice ◽

Central Myelin ◽

The Central Nervous System

Direct evidence has been presented to confirm the existence of a spiral in the myelin sheaths of the central nervous system. An account of some of the variations in structure of central myelin sheaths has been given and it has been shown that the radial component of myelin sheaths has the form of a series of rod-like thickenings of the intraperiod line. These thickenings extend along the intraperiod line in a direction parallel to the length of the axon. The relative position of the internal mesaxon and external tongue of cytoplasm has been determined in a number of transverse sections of sheaths from the optic nerves of adult mice, adult rats, and young rats. In about 75 per cent of the mature sheaths examined, these two structures were found within the same quadrant of the sheath, so that the cytoplasm of the external tongue process tends to lie directly outside that associated with the internal mesaxon. The frequency with which the internal mesaxon and external tongue lie within the same quadrant of the sheath increases both with the age of the animal and with the number of lamellae present within a sheath. The possible significance of these findings is discussed.

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Schwann cell remyelination of the central nervous system: why does it happen and what are the benefits?

Open Biology ◽

10.1098/rsob.200352 ◽

2021 ◽

Vol 11 (1) ◽

pp. 200352

Author(s):

Civia Z. Chen ◽

Björn Neumann ◽

Sarah Förster ◽

Robin J. M. Franklin

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Current Knowledge ◽

Oligodendrocyte Progenitor Cells ◽

Neuronal Function ◽

Lesion Area ◽

Myelin Sheaths ◽

The Central Nervous System ◽

Review Current ◽

Surprising Finding

Myelin sheaths, by supporting axonal integrity and allowing rapid saltatory impulse conduction, are of fundamental importance for neuronal function. In response to demyelinating injuries in the central nervous system (CNS), oligodendrocyte progenitor cells (OPCs) migrate to the lesion area, proliferate and differentiate into new oligodendrocytes that make new myelin sheaths. This process is termed remyelination. Under specific conditions, demyelinated axons in the CNS can also be remyelinated by Schwann cells (SCs), the myelinating cell of the peripheral nervous system. OPCs can be a major source of these CNS-resident SCs—a surprising finding given the distinct embryonic origins, and physiological compartmentalization of the peripheral and central nervous system. Although the mechanisms and cues governing OPC-to-SC differentiation remain largely undiscovered, it might nevertheless be an attractive target for promoting endogenous remyelination. This article will (i) review current knowledge on the origins of SCs in the CNS, with a particular focus on OPC to SC differentiation, (ii) discuss the necessary criteria for SC myelination in the CNS and (iii) highlight the potential of using SCs for myelin regeneration in the CNS.

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Fbxw7 is a critical regulator of Schwann cell myelinating potential

10.1101/342931 ◽

2018 ◽

Author(s):

Breanne L. Harty ◽

Fernanda Coelho ◽

Sarah D. Ackerman ◽

Amy L. Herbert ◽

David A. Lyons ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Ubiquitin Ligase ◽

E3 Ubiquitin Ligase ◽

Myelin Sheaths ◽

Unmyelinated Axons ◽

Single Axon ◽

The Central Nervous System ◽

Mutant Phenotypes ◽

Cns Myelination

SUMMARYMyelin insulates and protects axons in vertebrate nervous systems. In the central nervous system (CNS), oligodendrocytes (OLs) make numerous myelin sheaths on multiple axons, whereas in the peripheral nervous system (PNS) myelinating Schwann cells (SCs) make just one myelin sheath on a single axon. Why the myelinating potentials of OLs and SCs are so fundamentally different is unclear. Here, we find that loss of Fbxw7, an E3 ubiquitin ligase component, enhances the myelinating potential of SCs. Fbxw7 mutant SCs are seen myelinating multiple axons in a fashion reminiscent of OLs as well as aberrantly myelinating large axons while simultaneously ensheathing small unmyelinated axons - typically distinct roles of myelinating SCs and non-myelinating Remak SCs, respectively. We found that several of the Fbxw7 mutant phenotypes, including the ability to generate thicker myelin sheaths, were due to dysregulation of mTOR. However, the remarkable ability of mutant SCs to either myelinate multiple axons or myelinate some axons while simultaneously encompassing other unmyelinated axons is independent of mTOR signaling. This indicates distinct roles for Fbxw7 in regulating multiple aspects of SC behavior and that novel Fbxw7-regulated mechanisms control modes of myelination previously thought to fundamentally distinguish myelinating SCs from non-myelinating SCs and OLs. Our data reveal unexpected plasticity in the myelinating potential of SCs, which may have important implications for our understanding of both PNS and CNS myelination and myelin repair.

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Behaviour of oligodendrocytes and Schwann cells in an experimental model of toxic demyelination of the central nervous system

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2001000300009 ◽

2001 ◽

Vol 59 (2B) ◽

pp. 358-361 ◽

Cited By ~ 17

Author(s):

Dominguita Lühers Graça ◽

Eduardo Fernandes Bondan ◽

Luis Antonio Violin Dias Pereira ◽

Cristina Gevehr Fernandes ◽

Paulo César Maiorka

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Schwann Cells ◽

Experimental Model ◽

Glial Cells ◽

Ethidium Bromide ◽

Wistar Rats ◽

Myelin Sheaths ◽

Complex Processes ◽

The Central Nervous System

Oligodendrocytes and Schwann cells are engaged in myelin production, maintenance and repairing respectively in the central nervous system (CNS) and the peripheral nervous system (PNS). Whereas oligodendrocytes act only within the CNS, Schwann cells are able to invade the CNS in order to make new myelin sheaths around demyelinated axons. Both cells have some limitations in their activities, i.e. oligodendrocytes are post-mitotic cells and Schwann cells only get into the CNS in the absence of astrocytes. Ethidium bromide (EB) is a gliotoxic chemical that when injected locally within the CNS, induce demyelination. In the EB model of demyelination, glial cells are destroyed early after intoxication and Schwann cells are free to approach the naked central axons. In normal Wistar rats, regeneration of lost myelin sheaths can be achieved as early as thirteen days after intoxication; in Wistar rats immunosuppressed with cyclophosphamide the process is delayed and in rats administered cyclosporine it may be accelerated. Aiming the enlightening of those complex processes, all events concerning the myelinating cells in an experimental model are herein presented and discussed.

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Axonal mitochondria across species adjust in diameter depending on thickness of surrounding myelin

10.1101/850370 ◽

2019 ◽

Cited By ~ 2

Author(s):

Benjamin V Ineichen ◽

Keying Zhu ◽

Karl E Carlström

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Experimental Models ◽

Metabolic Status ◽

Myelinated Axons ◽

Myelin Sheaths ◽

Pathological Conditions ◽

The Central Nervous System ◽

Myelin Thickness

AbstractIn the central nervous system (CNS), axons and its surrounding myelin sheaths, generated by oligodendrocytes, greatly depend on each other, where oligodendrocytes provide axons with both trophic and metabolic support. Across spices, assessment of the axon-myelin ultrastructure is the key-approach to visualize de- and re-myelination of axons. However, this assessment omits to provide information on axonal homeostasis or how axon-myelin influence one another. Since mitochondria may adjust in size thus mirroring the intracellular physiological and metabolic status we applied this to myelinated axons in the CNS. We herein show that a large axonal mitochondria diameter correlates with thinner surrounding myelin sheaths across different CNS tracts and species, including human. We also show that the relation between axonal mitochondria diameter and surrounding myelin thickness is a valuable measurement to verify advanced remyelination in two commonly used experimental demyelinating models, namely the cuprizone and the lysolecithin (LPC) model. Lastly, we show that axonal mitochondria adjust in diameter in response to the thickness of the axonal surrounding myelin whereas the opposite adaption was absent. In summary, the link between axonal mitochondria diameter and surrounding myelin thickness provide insight on the axon-myelin relation both during homeostasis and pathological conditions. This link is also translational applicable and can thus contribute to a better understanding on how to study remyelination using experimental models.

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R-Ras GTPases Signaling Role in Myelin Neurodegenerative Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms21165911 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5911

Author(s):

Berta Alcover-Sanchez ◽

Gonzalo Garcia-Martin ◽

Francisco Wandosell ◽

Beatriz Cubelos

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Synaptic Transmission ◽

Neurodegenerative Diseases ◽

Progenitor Cells ◽

Oligodendrocyte Progenitor Cells ◽

Myelin Sheaths ◽

Ras Gtpases ◽

Complex Process ◽

The Central Nervous System

Myelination is required for fast and efficient synaptic transmission in vertebrates. In the central nervous system, oligodendrocytes are responsible for creating myelin sheaths that isolate and protect axons, even throughout adulthood. However, when myelin is lost, the failure of remyelination mechanisms can cause neurodegenerative myelin-associated pathologies. From oligodendrocyte progenitor cells to mature myelinating oligodendrocytes, myelination is a highly complex process that involves many elements of cellular signaling, yet many of the mechanisms that coordinate it, remain unknown. In this review, we will focus on the three major pathways involved in myelination (PI3K/Akt/mTOR, ERK1/2-MAPK, and Wnt/β-catenin) and recent advances describing the crosstalk elements which help to regulate them. In addition, we will review the tight relation between Ras GTPases and myelination processes and discuss its potential as novel elements of crosstalk between the pathways. A better understanding of the crosstalk elements orchestrating myelination mechanisms is essential to identify new potential targets to mitigate neurodegeneration.

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