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26 pages, 12601 KiB

Open AccessArticle

Identifying mRNAs Residing in Myelinating Oligodendrocyte Processes as a Basis for Understanding Internode Autonomy

by Robert Gould and Scott Brady

Life 2023, 13(4), 945; https://0-doi-org.brum.beds.ac.uk/10.3390/life13040945 - 04 Apr 2023

Cited by 1 | Viewed by 1822

In elaborating and maintaining myelin sheaths on multiple axons/segments, oligodendrocytes distribute translation of some proteins, including myelin basic protein (MBP), to sites of myelin sheath assembly, or MSAS. As mRNAs located at these sites are selectively trapped in myelin vesicles during tissue homogenization, [...] Read more.

In elaborating and maintaining myelin sheaths on multiple axons/segments, oligodendrocytes distribute translation of some proteins, including myelin basic protein (MBP), to sites of myelin sheath assembly, or MSAS. As mRNAs located at these sites are selectively trapped in myelin vesicles during tissue homogenization, we performed a screen to identify some of these mRNAs. To confirm locations, we used real-time quantitative polymerase chain reaction (RT-qPCR), to measure mRNA levels in myelin (M) and ‘non-myelin’ pellet (P) fractions, and found that five (LPAR1, TRP53INP2, TRAK2, TPPP, and SH3GL3) of thirteen mRNAs were highly enriched in myelin (M/P), suggesting residences in MSAS. Because expression by other cell-types will increase p-values, some MSAS mRNAs might be missed. To identify non-oligodendrocyte expression, we turned to several on-line resources. Although neurons express TRP53INP2, TRAK2 and TPPP mRNAs, these expressions did not invalidate recognitions as MSAS mRNAs. However, neuronal expression likely prevented recognition of KIF1A and MAPK8IP1 mRNAs as MSAS residents and ependymal cell expression likely prevented APOD mRNA assignment to MSAS. Complementary in situ hybridization (ISH) is recommended to confirm residences of mRNAs in MSAS. As both proteins and lipids are synthesized in MSAS, understanding myelination should not only include efforts to identify proteins synthesized in MSAS, but also the lipids. Full article

(This article belongs to the Special Issue Myelin and Oligodendrocyte-Neuron Interactions)

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17 pages, 4979 KiB

Open AccessArticle

New Species Can Broaden Myelin Research: Suitability of Little Skate, Leucoraja erinacea

by Wiebke Möbius, Sophie Hümmert, Torben Ruhwedel, Alan Kuzirian and Robert Gould

Life 2021, 11(2), 136; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020136 - 11 Feb 2021

Cited by 1 | Viewed by 2634

Abstract

Although myelinated nervous systems are shared among 60,000 jawed vertebrates, studies aimed at understanding myelination have focused more and more on mice and zebrafish. To obtain a broader understanding of the myelination process, we examined the little skate, Leucoraja erinacea. The reasons [...] Read more.

Although myelinated nervous systems are shared among 60,000 jawed vertebrates, studies aimed at understanding myelination have focused more and more on mice and zebrafish. To obtain a broader understanding of the myelination process, we examined the little skate, Leucoraja erinacea. The reasons behind initiating studies at this time include: the desire to study a species belonging to an out group of other jawed vertebrates; using a species with embryos accessible throughout development; the availability of genome sequences; and the likelihood that mammalian antibodies recognize homologs in the chosen species. We report that the morphological features of myelination in a skate hatchling, a stage that supports complex behavioral repertoires needed for survival, are highly similar in terms of: appearances of myelinating oligodendrocytes (CNS) and Schwann cells (PNS); the way their levels of myelination conform to axon caliber; and their identity in terms of nodal and paranodal specializations. These features provide a core for further studies to determine: axon–myelinating cell communication; the structures of the proteins and lipids upon which myelinated fibers are formed; the pathways used to transport these molecules to sites of myelin assembly and maintenance; and the gene regulatory networks that control their expressions. Full article

(This article belongs to the Special Issue Myelin and Oligodendrocyte-Neuron Interactions)

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Review

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15 pages, 1117 KiB

Open AccessReview

Oligodendrocyte Development and Regenerative Therapeutics in Multiple Sclerosis

by Nadjet Gacem and Brahim Nait-Oumesmar

Life 2021, 11(4), 327; https://0-doi-org.brum.beds.ac.uk/10.3390/life11040327 - 09 Apr 2021

Cited by 11 | Viewed by 5671

Abstract

Myelination by oligodendrocytes (OLs) is an important biological process essential for central nervous system (CNS) development and functions. Oligodendroglial lineage cells undergo several morphological and molecular changes at different stages of their lineage progression into myelinating OLs. The transition steps of the oligodendrocyte [...] Read more.

Myelination by oligodendrocytes (OLs) is an important biological process essential for central nervous system (CNS) development and functions. Oligodendroglial lineage cells undergo several morphological and molecular changes at different stages of their lineage progression into myelinating OLs. The transition steps of the oligodendrocyte progenitor cells (OPCs) to myelinating oligodendrocytes are defined by a specific pattern of regulated gene expression, which is under the control of coordinated signaling pathways. Any abnormal development, loss or failure of oligodendrocytes to myelinate axons can lead to several neurodegenerative diseases like multiple sclerosis (MS). MS is characterized by inflammation and demyelination, and current treatments target only the immune component of the disease, but have little impact on remyelination. Recently, several pharmacological compounds enhancing remyelination have been identified and some of them are in clinical trials. Here, we will review the current knowledge on oligodendrocyte differentiation, myelination and remyelination. We will focus on MS as a pathological condition, the most common chronic inflammatory demyelinating disease of the CNS in young adults. Full article

(This article belongs to the Special Issue Myelin and Oligodendrocyte-Neuron Interactions)

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19 pages, 1766 KiB

Open AccessReview

Oligodendroglial Energy Metabolism and (re)Myelination

by Vanja Tepavčević

Life 2021, 11(3), 238; https://0-doi-org.brum.beds.ac.uk/10.3390/life11030238 - 13 Mar 2021

Cited by 18 | Viewed by 5346

Abstract

Central nervous system (CNS) myelin has a crucial role in accelerating the propagation of action potentials and providing trophic support to the axons. Defective myelination and lack of myelin regeneration following demyelination can both lead to axonal pathology and neurodegeneration. Energy deficit has [...] Read more.

Central nervous system (CNS) myelin has a crucial role in accelerating the propagation of action potentials and providing trophic support to the axons. Defective myelination and lack of myelin regeneration following demyelination can both lead to axonal pathology and neurodegeneration. Energy deficit has been evoked as an important contributor to various CNS disorders, including multiple sclerosis (MS). Thus, dysregulation of energy homeostasis in oligodendroglia may be an important contributor to myelin dysfunction and lack of repair observed in the disease. This article will focus on energy metabolism pathways in oligodendroglial cells and highlight differences dependent on the maturation stage of the cell. In addition, it will emphasize that the use of alternative energy sources by oligodendroglia may be required to save glucose for functions that cannot be fulfilled by other metabolites, thus ensuring sufficient energy input for both myelin synthesis and trophic support to the axons. Finally, it will point out that neuropathological findings in a subtype of MS lesions likely reflect defective oligodendroglial energy homeostasis in the disease. Full article

(This article belongs to the Special Issue Myelin and Oligodendrocyte-Neuron Interactions)

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20 pages, 934 KiB

Open AccessReview

Interaction between Neurons and the Oligodendroglial Lineage in Multiple Sclerosis and Its Preclinical Models

by Vasiliki Pantazou, Thomas Roux, Vanessa Oliveira Moreira, Catherine Lubetzki and Anne Desmazières

Life 2021, 11(3), 231; https://0-doi-org.brum.beds.ac.uk/10.3390/life11030231 - 11 Mar 2021

Cited by 1 | Viewed by 2913

Abstract

Multiple sclerosis (MS) is a complex central nervous system inflammatory disease leading to demyelination and associated functional deficits. Though endogenous remyelination exists, it is only partial and, with time, patients can enter a progressive phase of the disease, with neurodegeneration as a hallmark. [...] Read more.

Multiple sclerosis (MS) is a complex central nervous system inflammatory disease leading to demyelination and associated functional deficits. Though endogenous remyelination exists, it is only partial and, with time, patients can enter a progressive phase of the disease, with neurodegeneration as a hallmark. Though major therapeutic advances have been made, with immunotherapies reducing relapse rate during the inflammatory phase of MS, there is presently no therapy available which significantly impacts disease progression. Remyelination has been shown to favor neuroprotection, and it is thus of major importance to better understand remyelination mechanisms in order to promote them and hence preserve neurons. A crucial point is how this process is regulated through the neuronal crosstalk with the oligodendroglial lineage. In this review, we present the current knowledge on neuron interaction with the oligodendroglial lineage, in physiological context as well as in MS and its experimental models. We further discuss the therapeutic possibilities resulting from this research field, which might allow to support remyelination and neuroprotection and thus limit MS progression. Full article

(This article belongs to the Special Issue Myelin and Oligodendrocyte-Neuron Interactions)

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21 pages, 1159 KiB

Open AccessReview

Neuron–Oligodendrocyte Communication in Myelination of Cortical GABAergic Cells

by Elisa Mazuir, Desdemona Fricker and Nathalie Sol-Foulon

Life 2021, 11(3), 216; https://0-doi-org.brum.beds.ac.uk/10.3390/life11030216 - 09 Mar 2021

Cited by 12 | Viewed by 6762

Abstract

Axonal myelination by oligodendrocytes increases the speed and reliability of action potential propagation, and so plays a pivotal role in cortical information processing. The extent and profile of myelination vary between different cortical layers and groups of neurons. Two subtypes of cortical GABAergic [...] Read more.

Axonal myelination by oligodendrocytes increases the speed and reliability of action potential propagation, and so plays a pivotal role in cortical information processing. The extent and profile of myelination vary between different cortical layers and groups of neurons. Two subtypes of cortical GABAergic neurons are myelinated: fast-spiking parvalbumin-expressing cells and somatostatin-containing cells. The expression of pre-nodes on the axon of these inhibitory cells before myelination illuminates communication between oligodendrocytes and neurons. We explore the consequences of myelination for action potential propagation, for patterns of neuronal connectivity and for the expression of behavioral plasticity. Full article

(This article belongs to the Special Issue Myelin and Oligodendrocyte-Neuron Interactions)

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11 pages, 636 KiB

Open AccessReview

Oligodendroglial Heterogeneity in Neuropsychiatric Disease

by Sunniva M. K. Bøstrand and Anna Williams

Life 2021, 11(2), 125; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020125 - 06 Feb 2021

Cited by 7 | Viewed by 2468

Abstract

Oligodendroglia interact with neurons to support their health and maintain the normal functioning of the central nervous system (CNS). Human oligodendroglia are a highly heterogeneous population characterised by distinct developmental origins and regional differences, as well as variation in cellular states, as evidenced [...] Read more.

Oligodendroglia interact with neurons to support their health and maintain the normal functioning of the central nervous system (CNS). Human oligodendroglia are a highly heterogeneous population characterised by distinct developmental origins and regional differences, as well as variation in cellular states, as evidenced by recent analysis at single-nuclei resolution. Increasingly, there is evidence to suggest that the highly heterogeneous nature of oligodendroglia might underpin their role in a range of CNS disorders, including those with neuropsychiatric symptoms. Understanding the role of oligodendroglial heterogeneity in this group of disorders might pave the way for novel approaches to identify biomarkers and develop treatments. Full article

(This article belongs to the Special Issue Myelin and Oligodendrocyte-Neuron Interactions)

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34 pages, 2151 KiB

Open AccessReview

Oligodendroglial Epigenetics, from Lineage Specification to Activity-Dependent Myelination

by Mathilde Pruvost and Sarah Moyon

Life 2021, 11(1), 62; https://0-doi-org.brum.beds.ac.uk/10.3390/life11010062 - 15 Jan 2021

Cited by 8 | Viewed by 3926

Abstract

Oligodendroglial cells are the myelinating cells of the central nervous system. While myelination is crucial to axonal activity and conduction, oligodendrocyte progenitor cells and oligodendrocytes have also been shown to be essential for neuronal support and metabolism. Thus, a tight regulation of oligodendroglial [...] Read more.

Oligodendroglial cells are the myelinating cells of the central nervous system. While myelination is crucial to axonal activity and conduction, oligodendrocyte progenitor cells and oligodendrocytes have also been shown to be essential for neuronal support and metabolism. Thus, a tight regulation of oligodendroglial cell specification, proliferation, and myelination is required for correct neuronal connectivity and function. Here, we review the role of epigenetic modifications in oligodendroglial lineage cells. First, we briefly describe the epigenetic modalities of gene regulation, which are known to have a role in oligodendroglial cells. We then address how epigenetic enzymes and/or marks have been associated with oligodendrocyte progenitor specification, survival and proliferation, differentiation, and finally, myelination. We finally mention how environmental cues, in particular, neuronal signals, are translated into epigenetic modifications, which can directly influence oligodendroglial biology. Full article

(This article belongs to the Special Issue Myelin and Oligodendrocyte-Neuron Interactions)

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17 pages, 6237 KiB

Open AccessReview

Implication of Contactins in Demyelinating Pathologies

by Ilias Kalafatakis, Maria Savvaki, Theodora Velona and Domna Karagogeos

Life 2021, 11(1), 51; https://0-doi-org.brum.beds.ac.uk/10.3390/life11010051 - 13 Jan 2021

Cited by 8 | Viewed by 2978

Abstract

Demyelinating pathologies comprise of a variety of conditions where either central or peripheral myelin is attacked, resulting in white matter lesions and neurodegeneration. Myelinated axons are organized into molecularly distinct domains, and this segregation is crucial for their proper function. These defined domains [...] Read more.

Demyelinating pathologies comprise of a variety of conditions where either central or peripheral myelin is attacked, resulting in white matter lesions and neurodegeneration. Myelinated axons are organized into molecularly distinct domains, and this segregation is crucial for their proper function. These defined domains are differentially affected at the different stages of demyelination as well as at the lesion and perilesion sites. Among the main players in myelinated axon organization are proteins of the contactin (CNTN) group of the immunoglobulin superfamily (IgSF) of cell adhesion molecules, namely Contactin-1 and Contactin-2 (CNTN1, CNTN2). The two contactins perform their functions through intermolecular interactions, which are crucial for myelinated axon integrity and functionality. In this review, we focus on the implication of these two molecules as well as their interactors in demyelinating pathologies in humans. At first, we describe the organization and function of myelinated axons in the central (CNS) and the peripheral (PNS) nervous system, further analyzing the role of CNTN1 and CNTN2 as well as their interactors in myelination. In the last section, studies showing the correlation of the two contactins with demyelinating pathologies are reviewed, highlighting the importance of these recognition molecules in shaping the function of the nervous system in multiple ways. Full article

(This article belongs to the Special Issue Myelin and Oligodendrocyte-Neuron Interactions)

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22 pages, 1705 KiB

Open AccessReview

Assembly and Function of the Juxtaparanodal Kv1 Complex in Health and Disease

by Delphine Pinatel and Catherine Faivre-Sarrailh

Life 2021, 11(1), 8; https://0-doi-org.brum.beds.ac.uk/10.3390/life11010008 - 24 Dec 2020

Cited by 8 | Viewed by 4726

Abstract

The precise axonal distribution of specific potassium channels is known to secure the shape and frequency of action potentials in myelinated fibers. The low-threshold voltage-gated Kv1 channels located at the axon initial segment have a significant influence on spike initiation and waveform. Their [...] Read more.

The precise axonal distribution of specific potassium channels is known to secure the shape and frequency of action potentials in myelinated fibers. The low-threshold voltage-gated Kv1 channels located at the axon initial segment have a significant influence on spike initiation and waveform. Their role remains partially understood at the juxtaparanodes where they are trapped under the compact myelin bordering the nodes of Ranvier in physiological conditions. However, the exposure of Kv1 channels in de- or dys-myelinating neuropathy results in alteration of saltatory conduction. Moreover, cell adhesion molecules associated with the Kv1 complex, including Caspr2, Contactin2, and LGI1, are target antigens in autoimmune diseases associated with hyperexcitability such as encephalitis, neuromyotonia, or neuropathic pain. The clustering of Kv1.1/Kv1.2 channels at the axon initial segment and juxtaparanodes is based on interactions with cell adhesion molecules and cytoskeletal linkers. This review will focus on the trafficking and assembly of the axonal Kv1 complex in the peripheral and central nervous system (PNS and CNS), during development, and in health and disease. Full article

(This article belongs to the Special Issue Myelin and Oligodendrocyte-Neuron Interactions)

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