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Cells
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Structure and Function of Healthy and Diseased Myelin
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Structure and Function of Healthy and Diseased Myelin

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (31 January 2020) | Viewed by 45204

Special Issue Information

Dear Colleagues,

Myelin is a specialized biomembrane in the nervous system of vertebrates, although myelin-like structures can be detected in lower organisms. The unique, restricted biochemical composition of the myelin membrane allows it to form multilayered structures and to carry out specific functions, but also makes it prone to disease-inducing mutations that affect its molecular components. While the function of myelin was for a long time thought to simply enable saltatory nerve impulse conduction, intense research during recent years has drawn a much more complex picture of myelin biochemistry. Metabolic, trophic, and signalling functions are now recognized components of the functional repertoire of myelin sheaths. A coordinated interplay between the myelinating cell cytoskeleton, proteins residing on the myelin membrane, and extracellular ligands is crucial for the correct formation and stability of myelin. Meanwhile, the molecular structure of the myelin proteolipid membrane at high resolution remains to be visualized. Studies in recent years have provided a wealth of data on the structure and properties of myelin molecules, including integral membrane proteins. We can expect a more complete structural description of the native myelin membrane at the molecular level in the future.

This Special Issue of Cells will welcome papers on all aspects of myelin research, from theoretical and basic science to applications and myelin disease. It aims to provide an update on different fields of myelin-related research, to enable an overall understanding of myelin structure and function at different levels of complexity. 

Petri Kursula
Guest Editor

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Keywords

  • myelin
  • membrane
  • neurobiology
  • demyelination
  • structural biology

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Published Papers (6 papers)

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Research

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12 pages, 1580 KiB  
Article
Phase Diagram of Purified CNS Myelin Reveals Continuous Transformation between Expanded and Compacted Lamellar States
by Julio M. Pusterla, Emanuel Schneck and Rafael G. Oliveira
Cells 2020, 9(3), 670; https://doi.org/10.3390/cells9030670 - 10 Mar 2020
Cited by 3 | Viewed by 2635
Abstract
Purified myelin membranes (PMMs) are the starting material for biochemical studies, from individual components up to the isolation of detergent-resistant membrane (DRM) fractions or detergent-insoluble glycosphingolipid (DIG) fractions, which are commonly believed to resemble physiological lipid rafts. The normal DIG isolation protocol involves [...] Read more.
Purified myelin membranes (PMMs) are the starting material for biochemical studies, from individual components up to the isolation of detergent-resistant membrane (DRM) fractions or detergent-insoluble glycosphingolipid (DIG) fractions, which are commonly believed to resemble physiological lipid rafts. The normal DIG isolation protocol involves the extraction of lipids under moderate cooling. The isolation of PMMs also involves the cooling of myelin as well as exposure to low ionic strength (IS). Here, we addressed the combined influence of cooling and IS on the structure of PMMs. The phase behaviour was investigated by small angle X-ray diffraction. Analysis of the diffraction peaks revealed the lamellar periodicity ( d ), the number of periodically correlated bilayers ( N ), and the relatives fractions of each phase. Departure from physiological conditions induced a phase separation in myelin. The effect of monovalent and divalent ions was also compared at equivalent IS, showing a differential effect, and phase diagrams for both ion types were established—Ca2+ induced the well-known over-compacted phase, but additionally we also found an expanded phase at low IS. Na+ promoted phase separation, and also induced over-compaction at sufficiently high IS. Finally, exploring the whole phase diagram, we found evidence for the direct isothermal transformation from the expanded to the compacted phase, suggesting that both phases could in fact originate from the identical primary lateral phase separation, whereas the apparent difference lies in the inter-bilayer interaction that is modulated by the ionic milieu. Full article
(This article belongs to the Special Issue Structure and Function of Healthy and Diseased Myelin)
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18 pages, 4408 KiB  
Article
Effect of Cholesterol and Myelin Basic Protein (MBP) Content on Lipid Monolayers Mimicking the Cytoplasmic Membrane of Myelin
by Jennica Träger, Katharina Widder, Andreas Kerth, George Harauz and Dariush Hinderberger
Cells 2020, 9(3), 529; https://doi.org/10.3390/cells9030529 - 25 Feb 2020
Cited by 18 | Viewed by 3785
Abstract
Myelin basic protein (MBP) is located in the insulating covers of nerve cells in the brain and spinal cord. By interacting with lipid membranes, it is responsible for compaction of the myelin sheath in the central nervous system, which is weakened in demyelinating [...] Read more.
Myelin basic protein (MBP) is located in the insulating covers of nerve cells in the brain and spinal cord. By interacting with lipid membranes, it is responsible for compaction of the myelin sheath in the central nervous system, which is weakened in demyelinating diseases. The lipid composition of the myelin leaflet has a high impact on the interaction between the membrane and MBP. Cholesterol is present in the cytoplasmic leaflet with a rather high amount of 44% (mol%). In this study, the focus is on the effect of cholesterol, mainly by varying its content, on the interaction of MBP with a lipid monolayer. Therefore, Langmuir lipid monolayers mimicking the cytoplasmic membrane of myelin and monolayers with variations of cholesterol content between 0% and 100% were measured at the air/water interface with additional imaging by fluorescence microscopy. All experiments were performed with and without bovine MBP to study the dependence of the interaction of the protein with the monolayers on the cholesterol content. The native amount of 44% cholesterol in the monolayer combines optima in the order of the monolayer (presumably correlating to compaction and thermodynamic stability) and protein interaction and shows unique features in comparison to lower or higher cholesterol contents. Full article
(This article belongs to the Special Issue Structure and Function of Healthy and Diseased Myelin)
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14 pages, 1741 KiB  
Article
Myelin Measurement Using Quantitative Magnetic Resonance Imaging: A Correlation Study Comparing Various Imaging Techniques in Patients with Multiple Sclerosis
by Laetitia Saccenti, Akifumi Hagiwara, Christina Andica, Kazumasa Yokoyama, Shohei Fujita, Shimpei Kato, Tomoko Maekawa, Koji Kamagata, Alice Le Berre, Masaaki Hori, Akihiko Wada, Ukihide Tateishi, Nobutaka Hattori and Shigeki Aoki
Cells 2020, 9(2), 393; https://doi.org/10.3390/cells9020393 - 8 Feb 2020
Cited by 25 | Viewed by 6248
Abstract
Evaluation of myelin by magnetic resonance imaging (MRI) is a difficult challenge, but holds promise in demyelinating diseases, such as multiple sclerosis (MS). Although multiple techniques have been developed, no gold standard has been established. This study aims to evaluate the correlation between [...] Read more.
Evaluation of myelin by magnetic resonance imaging (MRI) is a difficult challenge, but holds promise in demyelinating diseases, such as multiple sclerosis (MS). Although multiple techniques have been developed, no gold standard has been established. This study aims to evaluate the correlation between synthetic MRI myelin volume fraction (SyMRIMVF) and myelin fraction estimated by other techniques, i.e., magnetization transfer saturation (MTsat), T1-weighted images divided by T2-weighted images (T1w/T2w), and radial diffusivity (RD) in patients with MS. We also compared the sensitivities of these techniques for detecting MS-related myelin damage. SyMRIMVF, MTsat, T1w/T2w, and RD were averaged on plaque, periplaque white matter, and normal-appearing white matter (NAWM). Pairwise correlation was calculated using Spearman’s correlation analysis. For all segmented regions, strong correlations were found between SyMRIMVF and T1w/T2w (Rho = 0.89), MTsat (Rho = 0.82), or RD (Rho = −0.75). For each technique, the average estimated myelin differed significantly among regions, but the percentage change of NAWM from both periplaque white matter and plaque were highest in SyMRIMVF. SyMRIMVF might be suitable for myelin evaluation in MS patients, with relevant results as compared to other well-studied techniques. Moreover, it presented better sensitivity for the detection of the difference between plaque or periplaque white matter and NAWM. Full article
(This article belongs to the Special Issue Structure and Function of Healthy and Diseased Myelin)
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17 pages, 4336 KiB  
Article
Spectral Characterization of Stem Cell-Derived Myelination within the Injured Adult PNS Using the Solvatochromic Dye Nile Red
by Joey Grochmal, Wulin Teo, Hardeep Gambhir, Ranjan Kumar, Jo Anne Stratton, Raveena Dhaliwal, Craig Brideau, Jeff Biernaskie, Peter Stys and Rajiv Midha
Cells 2020, 9(1), 189; https://doi.org/10.3390/cells9010189 - 11 Jan 2020
Viewed by 4516
Abstract
Background: Myelin is an essential component of the peripheral and central nervous system, enabling fast axonal conduction and supporting axonal integrity; limited tools exist for analysis of myelin composition in-vivo. Objective: To demonstrate that the photophysical properties of myelin-incorporated solvatochromic dyes can be [...] Read more.
Background: Myelin is an essential component of the peripheral and central nervous system, enabling fast axonal conduction and supporting axonal integrity; limited tools exist for analysis of myelin composition in-vivo. Objective: To demonstrate that the photophysical properties of myelin-incorporated solvatochromic dyes can be exploited to probe the biochemical composition of living peripheral nerve myelin at high spatial resolution. Methods: Using the myelin-incorporated fluorescent dye Nile Red we sequentially analyzed the spectral characteristics of remyelinating myelin membranes both in-vitro and in-vivo, including in living rats. Results: We demonstrated a consistent bi-phasic evolution of emission spectra during early remyelination, and visually report the reliable biochemical flux of myelin membrane composition in-vitro and in-vivo. Conclusions: Solvatochromic spectroscopy enables the analysis of myelin membrane maturity during remyelination, and can be performed in-vivo. As the formation of myelin during early-to-late remyelination likely incorporates fluctuating fractions of lipophilic components and changes in lateral membrane mobility, we propose that our spectrochemical data reflects the observation of these biochemical processes. Full article
(This article belongs to the Special Issue Structure and Function of Healthy and Diseased Myelin)
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Review

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17 pages, 1153 KiB  
Review
Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism
by Yannick Poitelon, Ashley M. Kopec and Sophie Belin
Cells 2020, 9(4), 812; https://doi.org/10.3390/cells9040812 - 27 Mar 2020
Cited by 185 | Viewed by 16773
Abstract
Myelin is critical for the proper function of the nervous system and one of the most complex cell–cell interactions of the body. Myelination allows for the rapid conduction of action potentials along axonal fibers and provides physical and trophic support to neurons. Myelin [...] Read more.
Myelin is critical for the proper function of the nervous system and one of the most complex cell–cell interactions of the body. Myelination allows for the rapid conduction of action potentials along axonal fibers and provides physical and trophic support to neurons. Myelin contains a high content of lipids, and the formation of the myelin sheath requires high levels of fatty acid and lipid synthesis, together with uptake of extracellular fatty acids. Recent studies have further advanced our understanding of the metabolism and functions of myelin fatty acids and lipids. In this review, we present an overview of the basic biology of myelin lipids and recent insights on the regulation of fatty acid metabolism and functions in myelinating cells. In addition, this review may serve to provide a foundation for future research characterizing the role of fatty acids and lipids in myelin biology and metabolic disorders affecting the central and peripheral nervous system. Full article
(This article belongs to the Special Issue Structure and Function of Healthy and Diseased Myelin)
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33 pages, 5952 KiB  
Review
Flexible Players within the Sheaths: The Intrinsically Disordered Proteins of Myelin in Health and Disease
by Arne Raasakka and Petri Kursula
Cells 2020, 9(2), 470; https://doi.org/10.3390/cells9020470 - 18 Feb 2020
Cited by 15 | Viewed by 10403 | Correction
Abstract
Myelin ensheathes selected axonal segments within the nervous system, resulting primarily in nerve impulse acceleration, as well as mechanical and trophic support for neurons. In the central and peripheral nervous systems, various proteins that contribute to the formation and stability of myelin are [...] Read more.
Myelin ensheathes selected axonal segments within the nervous system, resulting primarily in nerve impulse acceleration, as well as mechanical and trophic support for neurons. In the central and peripheral nervous systems, various proteins that contribute to the formation and stability of myelin are present, which also harbor pathophysiological roles in myelin disease. Many myelin proteins have common attributes, including small size, hydrophobic segments, multifunctionality, longevity, and regions of intrinsic disorder. With recent advances in protein biophysical characterization and bioinformatics, it has become evident that intrinsically disordered proteins (IDPs) are abundant in myelin, and their flexible nature enables multifunctionality. Here, we review known myelin IDPs, their conservation, molecular characteristics and functions, and their disease relevance, along with open questions and speculations. We place emphasis on classifying the molecular details of IDPs in myelin, and we correlate these with their various functions, including susceptibility to post-translational modifications, function in protein–protein and protein–membrane interactions, as well as their role as extended entropic chains. We discuss how myelin pathology can relate to IDPs and which molecular factors are potentially involved. Full article
(This article belongs to the Special Issue Structure and Function of Healthy and Diseased Myelin)
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