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Glia Aug 2015In the peripheral nervous system, Schwann cells are glial cells that are in intimate contact with axons throughout development. Schwann cells generate the insulating... (Review)
Review
In the peripheral nervous system, Schwann cells are glial cells that are in intimate contact with axons throughout development. Schwann cells generate the insulating myelin sheath and provide vital trophic support to the neurons that they ensheathe. Schwann cell precursors arise from neural crest progenitor cells, and a highly ordered developmental sequence controls the progression of these cells to become mature myelinating or nonmyelinating Schwann cells. Here, we discuss both seminal discoveries and recent advances in our understanding of the molecular mechanisms that drive Schwann cell development and myelination with a focus on cell-cell and cell-matrix signaling events.
Topics: Animals; Humans; Myelin Sheath; Neural Stem Cells; Schwann Cells
PubMed: 25921593
DOI: 10.1002/glia.22852 -
Journal of Neuroscience Research Nov 2009Myelin-associated glycoprotein (MAG) is expressed on the innermost myelin membrane wrap, directly apposed to the axon surface. Although it is not required for... (Review)
Review
Myelin-associated glycoprotein (MAG) is expressed on the innermost myelin membrane wrap, directly apposed to the axon surface. Although it is not required for myelination, MAG enhances long-term axon-myelin stability, helps to structure nodes of Ranvier, and regulates the axon cytoskeleton. In addition to its role in axon-myelin stabilization, MAG inhibits axon regeneration after injury; MAG and a discrete set of other molecules on residual myelin membranes at injury sites actively signal axons to halt elongation. Both the stabilizing and the axon outgrowth inhibitory effects of MAG are mediated by complementary MAG receptors on the axon surface. Two MAG receptor families have been described, sialoglycans (specifically gangliosides GD1a and GT1b) and Nogo receptors (NgRs). Controversies remain about which receptor(s) mediates which of MAG's biological effects. Here we review the findings and challenges in associating MAG's biological effects with specific receptors.
Topics: Animals; Gangliosides; Growth Cones; Growth Inhibitors; Humans; Myelin Proteins; Myelin Sheath; Myelin-Associated Glycoprotein; Nerve Fibers, Myelinated; Nogo Proteins; Receptors, Cell Surface; Signal Transduction
PubMed: 19156870
DOI: 10.1002/jnr.21992 -
Nature Reviews. Neurology May 2010The myelin sheath wraps large axons in both the CNS and the PNS, and is a key determinant of efficient axonal function and health. Myelin is targeted in a series of... (Review)
Review
The myelin sheath wraps large axons in both the CNS and the PNS, and is a key determinant of efficient axonal function and health. Myelin is targeted in a series of diseases, notably multiple sclerosis (MS). In MS, demyelination is associated with progressive axonal damage, which determines the level of patient disability. The few treatments that are available for combating myelin damage in MS and related disorders, which largely comprise anti-inflammatory drugs, only show limited efficacy in subsets of patients. More-effective treatment of myelin disorders will probably be accomplished by early intervention with combinatorial therapies that target inflammation and other processes-for example, signaling pathways that promote remyelination. Indeed, evidence suggests that such pathways might be impaired in pathology and, hence, contribute to the failure of remyelination in such diseases. In this article, we review the molecular basis of signaling pathways that regulate myelination in the CNS and PNS, with a focus on signals that affect differentiation of myelinating glia. We also discuss factors such as extracellular molecules that act as modulators of these pathways. Finally, we consider the few preclinical and clinical trials of agents that augment this signaling.
Topics: Animals; Anti-Inflammatory Agents; Humans; Models, Biological; Multiple Sclerosis; Myelin Sheath; Nerve Regeneration; Nerve Tissue Proteins; Nervous System Physiological Phenomena; Signal Transduction
PubMed: 20404842
DOI: 10.1038/nrneurol.2010.37 -
The Journal of Physiological Sciences :... Mar 2016Rapid action potential propagation along myelinated axons requires voltage-gated Na(+) channel clustering at the axon initial segments (AISs) and nodes of Ranvier. The... (Review)
Review
Rapid action potential propagation along myelinated axons requires voltage-gated Na(+) channel clustering at the axon initial segments (AISs) and nodes of Ranvier. The AIS is intrinsically defined by cytoskeletal proteins expressed in axons, whereas nodes of Ranvier are formed by interaction between neurons and myelinating glia. These axonal domains have long been considered stable structures, but recent studies revealed that they are plastic and contribute to fine adjustment of neuronal activities and circuit function. The AIS changes its distribution and maintains neural circuit activity at a constant level. Morphological changes in myelinated nerve structures presumably modulate the excitability of nodal regions and regulate the timing of activity, thereby optimizing signal processing in a neural circuit. This review highlights recent findings on the structural plasticity of these excitable axonal domains.
Topics: Action Potentials; Animals; Axons; Myelin Sheath; Neuroglia; Neuronal Plasticity
PubMed: 26464228
DOI: 10.1007/s12576-015-0413-4 -
Molecular Metabolism Mar 2023Oligodendrocyte progenitor cell differentiation is regulated by nutritional signals in the adult median eminence (ME), but the consequences on local myelination are...
OBJECTIVE
Oligodendrocyte progenitor cell differentiation is regulated by nutritional signals in the adult median eminence (ME), but the consequences on local myelination are unknown. The aim of this study was to characterize myelin plasticity in the ME of adult mice in health or in response to chronic nutritional challenge and determine its relevance to the regulation of energy balance.
METHODS
We assessed new oligodendrocyte (OL) and myelin generation and stability in the ME of healthy adult male mice using bromodeoxyuridine labelling and genetic fate mapping tools. We evaluated the contribution of microglia to ME myelin plasticity in PLX5622-treated C57BL/6J mice and in Pdgfra-Cre/ER;R26R-eYFP;Myrf mice, where adult oligodendrogenesis is blunted. Next, we investigated how high-fat feeding or caloric restriction impact ME OL lineage progression and myelination. Finally, we characterized the functional relevance of adult oligodendrogenesis on energy balance regulation.
RESULTS
We show that myelinating OLs are continuously and rapidly generated in the adult ME. Paradoxically, OL number and myelin amounts remain remarkably stable in the adult ME. In fact, the high rate of new OL and myelin generation in the ME is offset by continuous turnover of both. We show that microglia are required for continuous OL and myelin production, and that ME myelin plasticity regulates the recruitment of local immune cells. Finally, we provide evidence that ME myelination is regulated by the body's energetic status and demonstrate that ME OL and myelin plasticity are required for the regulation of energy balance and hypothalamic leptin sensitivity.
CONCLUSIONS
This study identifies a new mechanism modulating leptin sensitivity and the central control of energy balance and uncovers a previously unappreciated form of structural plasticity in the ME.
Topics: Mice; Male; Animals; Myelin Sheath; Leptin; Mice, Transgenic; Median Eminence; Mice, Inbred C57BL
PubMed: 36739968
DOI: 10.1016/j.molmet.2023.101690 -
Glia Dec 2022Peripheral nerves and Schwann cells have to sustain constant mechanical constraints, caused by developmental growth as well as stretches associated with movements of the...
Peripheral nerves and Schwann cells have to sustain constant mechanical constraints, caused by developmental growth as well as stretches associated with movements of the limbs and mechanical compressions from daily activities. In Schwann cells, signaling molecules sensitive to stiffness or stretch of the extracellular matrix, such as YAP/TAZ, have been shown to be critical for Schwann cell development and peripheral nerve regeneration. YAP/TAZ have also been suggested to contribute to tumorigenesis, neuropathic pain, and inherited disorders. Yet, the role of mechanosensitive ion channels in myelinating Schwann cells is vastly unexplored. Here we comprehensively assessed the expression of mechanosensitive ion channels in Schwann cells and identified that PIEZO1 and PIEZO2 are among the most abundant mechanosensitive ion channels expressed by Schwann cells. Using classic genetic ablation studies, we show that PIEZO1 is a transient inhibitor of radial and longitudinal myelination in Schwann cells. Contrastingly, we show that PIEZO2 may be required for myelin formation, as the absence of PIEZO2 in Schwann cells delays myelin formation. We found an epistatic relationship between PIEZO1 and PIEZO2, at both the morphological and molecular levels. Finally, we show that PIEZO1 channels affect the regulation of YAP/TAZ activation in Schwann cells. Overall, we present here the first demonstration that PIEZO1 and PIEZO2 contribute to mechanosensation in Schwann cells as well myelin development in the peripheral nervous system.
Topics: Ion Channels; Myelin Sheath; Neurogenesis; Schwann Cells
PubMed: 35903933
DOI: 10.1002/glia.24251 -
Neuroscience Sep 2014Myelination by oligodendrocytes is a highly specialized process that relies on intimate interactions between the axon and the oligodendrocytes. Astrocytes have an... (Review)
Review
Myelination by oligodendrocytes is a highly specialized process that relies on intimate interactions between the axon and the oligodendrocytes. Astrocytes have an important part in facilitating myelination in the CNS, however, comparatively less is known about how they affect myelination. This review therefore summarizes the literature and explores lingering questions surrounding differences between white matter and gray matter astrocytes, how astrocytes support myelination, how their dysfunction in pathological states contributes to myelin pathologies and how astrocytes may facilitate remyelination. We discuss how astrocytes in the white matter are specialized to promote myelination and myelin maintenance by clearance of extracellular ions and neurotransmitters and by secretion of pro-myelinating factors. Additionally, astrocyte-oligodendrocyte coupling via gap junctions is crucial for both myelin formation and maintenance, due to K(+) buffering and possibly metabolic support for oligodendrocytes via the panglial syncytium. Dysfunctional astrocytes aberrantly affect oligodendrocytes, as exemplified by a number of leukodystrophies in which astrocytic pathology is known as the direct cause of myelin pathology. Conversely, in primary demyelinating diseases, such as multiple sclerosis, astrocytes may facilitate remyelination. We suggest that specific manipulation of astrocytes could help prevent myelin pathologies and successfully restore myelin sheaths after demyelination.
Topics: Animals; Astrocytes; Gray Matter; Humans; Multiple Sclerosis; Myelin Sheath; Oligodendroglia; White Matter
PubMed: 24231735
DOI: 10.1016/j.neuroscience.2013.10.050 -
Journal of Neurochemistry Feb 2019Myelin, the multilayered membrane surrounding many axons in the nervous system, increases the speed by which electrical signals travel along axons and facilitates... (Review)
Review
Myelin, the multilayered membrane surrounding many axons in the nervous system, increases the speed by which electrical signals travel along axons and facilitates neuronal communication between distant regions of the nervous system. However, how neuronal signals influence the myelinating process in the CNS is still largely unclear. Recent studies have significantly advanced this understanding, identifying important roles for neuronal activity in controlling oligodendrocyte development and their capacity of producing myelin in both developing and mature CNS. Here, we review these recent advances, and discuss potential mechanisms underpinning activity-dependent myelination and how remyelination may be stimulated via manipulating axonal activity, raising new questions for future research.
Topics: Animals; Cell Differentiation; Central Nervous System; Humans; Myelin Sheath; Neurogenesis; Oligodendroglia
PubMed: 30225984
DOI: 10.1111/jnc.14592 -
Advances in Biological Regulation Jan 2019The myelin sheath, produced by oligodendrocytes in the central nervous system, provides essential electrical insulation to neurons, but also is critical for viability of... (Review)
Review
The myelin sheath, produced by oligodendrocytes in the central nervous system, provides essential electrical insulation to neurons, but also is critical for viability of neurons. Both the protein and lipid composition of this fascinating membrane is unique. Here the focus is on the sphingolipids that are highly abundant in myelin and, in particular, how they are produced. This review discusses how sphingolipid metabolism is regulated. In particular the subcellular localization of lipid metabolic enzymes is discussed and how inter-organelle transport can affect the metabolic routes that sphingolipid precursors take. Understanding the regulation of sphingolipid metabolism in formation of the myelin membrane will have a significant impact on strategies to treat demyelinating diseases.
Topics: Animals; Biological Transport, Active; Central Nervous System; Demyelinating Diseases; Humans; Myelin Sheath; Oligodendroglia; Sphingolipids
PubMed: 30497846
DOI: 10.1016/j.jbior.2018.11.002 -
The Neuroscientist : a Review Journal... Feb 2012Myelination of axons by oligodendrocytes and Schwann cells in the central and peripheral nervous system, respectively, is essential for normal neuronal functions, and... (Review)
Review
Myelination of axons by oligodendrocytes and Schwann cells in the central and peripheral nervous system, respectively, is essential for normal neuronal functions, and its failure results in devastating demyelinating diseases. During development, both oligodendrocyte and Schwann cell precursors undergo a temporally well-defined series of molecular and structural changes, ultimately culminating in the cessation of proliferation and the elaboration of a highly complex myelin sheath. Recent studies have demonstrated a critical role of microRNAs (miRNAs) in the progression of oligodendrocyte and Schwann cell precursors to the myelinating state-depletion of miRNAs from either cell type results in an arrest in differentiation and lack of myelination. Furthermore, these studies have begun to elucidate the dynamic regulation of miRNA expression and the complexity of miRNA-mediated gene regulation during differentiation of myelinating cells. In this review, the authors highlight the recent understanding of functional links of miRNAs to regulatory networks for central and peripheral myelination, as well as perspectives on the role of miRNAs in demyelinating diseases.
Topics: Animals; Astrocytes; Axons; Cell Differentiation; Demyelinating Diseases; Gene Expression Regulation; Humans; Mice; Mice, Knockout; MicroRNAs; Myelin Sheath; Neurons; Oligodendroglia; Schwann Cells
PubMed: 21536841
DOI: 10.1177/1073858410392382