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Cold Spring Harbor Perspectives in... Jun 2015Myelinated nerve fibers have evolved to enable fast and efficient transduction of electrical signals in the nervous system. To act as an electric insulator, the myelin... (Review)
Review
Myelinated nerve fibers have evolved to enable fast and efficient transduction of electrical signals in the nervous system. To act as an electric insulator, the myelin sheath is formed as a multilamellar membrane structure by the spiral wrapping and subsequent compaction of the oligodendroglial plasma membrane around central nervous system (CNS) axons. Current evidence indicates that the myelin sheath is more than an inert insulating membrane structure. Oligodendrocytes are metabolically active and functionally connected to the subjacent axon via cytoplasmic-rich myelinic channels for movement of macromolecules to and from the internodal periaxonal space under the myelin sheath. This review summarizes our current understanding of how myelin is generated and also the role of oligodendrocytes in supporting the long-term integrity of myelinated axons.
Topics: Axons; Glycolysis; Models, Biological; Myelin Sheath; Oligodendroglia; Synaptic Transmission
PubMed: 26101081
DOI: 10.1101/cshperspect.a020479 -
Physiological Reviews Jul 2019Oligodendrocytes generate multiple layers of myelin membrane around axons of the central nervous system to enable fast and efficient nerve conduction. Until recently,... (Review)
Review
Oligodendrocytes generate multiple layers of myelin membrane around axons of the central nervous system to enable fast and efficient nerve conduction. Until recently, saltatory nerve conduction was considered the only purpose of myelin, but it is now clear that myelin has more functions. In fact, myelinating oligodendrocytes are embedded in a vast network of interconnected glial and neuronal cells, and increasing evidence supports an active role of oligodendrocytes within this assembly, for example, by providing metabolic support to neurons, by regulating ion and water homeostasis, and by adapting to activity-dependent neuronal signals. The molecular complexity governing these interactions requires an in-depth molecular understanding of how oligodendrocytes and axons interact and how they generate, maintain, and remodel their myelin sheaths. This review deals with the biology of myelin, the expanded relationship of myelin with its underlying axons and the neighboring cells, and its disturbances in various diseases such as multiple sclerosis, acute disseminated encephalomyelitis, and neuromyelitis optica spectrum disorders. Furthermore, we will highlight how specific interactions between astrocytes, oligodendrocytes, and microglia contribute to demyelination in hereditary white matter pathologies.
Topics: Aging; Animals; Central Nervous System; Demyelinating Diseases; Humans; Myelin Sheath
PubMed: 31066630
DOI: 10.1152/physrev.00031.2018 -
Cold Spring Harbor Perspectives in... Jun 2015Myelinated nerve fibers are essential for the rapid propagation of action potentials by saltatory conduction. They form as the result of reciprocal interactions between... (Review)
Review
Myelinated nerve fibers are essential for the rapid propagation of action potentials by saltatory conduction. They form as the result of reciprocal interactions between axons and Schwann cells. Extrinsic signals from the axon, and the extracellular matrix, drive Schwann cells to adopt a myelinating fate, whereas myelination reorganizes the axon for its role in conduction and is essential for its integrity. Here, we review our current understanding of the development, molecular organization, and function of myelinating Schwann cells. Recent findings into the extrinsic signals that drive Schwann cell myelination, their cognate receptors, and the downstream intracellular signaling pathways they activate will be described. Together, these studies provide important new insights into how these pathways converge to activate the transcriptional cascade of myelination and remodel the actin cytoskeleton that is critical for morphogenesis of the myelin sheath.
Topics: Action Potentials; Epigenesis, Genetic; Humans; Myelin Sheath; Nerve Fibers, Myelinated; Schwann Cells; Signal Transduction; Transcription, Genetic
PubMed: 26054742
DOI: 10.1101/cshperspect.a020529 -
Proceedings of the National Academy of... Oct 2019Observing the structure and regeneration of the myelin sheath in peripheral nerves following injury and during repair would help in understanding the pathogenesis and...
Observing the structure and regeneration of the myelin sheath in peripheral nerves following injury and during repair would help in understanding the pathogenesis and treatment of neurological diseases caused by an abnormal myelin sheath. In the present study, transmission electron microscopy, immunofluorescence staining, and transcriptome analyses were used to investigate the structure and regeneration of the myelin sheath after end-to-end anastomosis, autologous nerve transplantation, and nerve tube transplantation in a rat model of sciatic nerve injury, with normal optic nerve, oculomotor nerve, sciatic nerve, and Schwann cells used as controls. The results suggested that the double-bilayer was the structural unit that constituted the myelin sheath. The major feature during regeneration was the compaction of the myelin sheath, wherein the distance between the 2 layers of cell membrane in the double-bilayer became shorter and the adjacent double-bilayers tightly closed together and formed the major dense line. The expression level of myelin basic protein was positively correlated with the formation of the major dense line, and the compacted myelin sheath could not be formed without the anchoring of the lipophilin particles to the myelin sheath.
Topics: Animals; Axons; Myelin Sheath; Nerve Regeneration; Peripheral Nerve Injuries; Rats
PubMed: 31611410
DOI: 10.1073/pnas.1910292116 -
Cells Mar 2020Myelin 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... (Review)
Review
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.
Topics: Animals; Fatty Acids; Humans; Lipid Metabolism; Models, Biological; Myelin Sheath; Oxidation-Reduction
PubMed: 32230947
DOI: 10.3390/cells9040812 -
The Journal of Physiology Jul 2016Nerve injury triggers the conversion of myelin and non-myelin (Remak) Schwann cells to a cell phenotype specialized to promote repair. Distal to damage, these repair... (Review)
Review
Nerve injury triggers the conversion of myelin and non-myelin (Remak) Schwann cells to a cell phenotype specialized to promote repair. Distal to damage, these repair Schwann cells provide the necessary signals and spatial cues for the survival of injured neurons, axonal regeneration and target reinnervation. The conversion to repair Schwann cells involves de-differentiation together with alternative differentiation, or activation, a combination that is typical of cell type conversions often referred to as (direct or lineage) reprogramming. Thus, injury-induced Schwann cell reprogramming involves down-regulation of myelin genes combined with activation of a set of repair-supportive features, including up-regulation of trophic factors, elevation of cytokines as part of the innate immune response, myelin clearance by activation of myelin autophagy in Schwann cells and macrophage recruitment, and the formation of regeneration tracks, Bungner's bands, for directing axons to their targets. This repair programme is controlled transcriptionally by mechanisms involving the transcription factor c-Jun, which is rapidly up-regulated in Schwann cells after injury. In the absence of c-Jun, damage results in the formation of a dysfunctional repair cell, neuronal death and failure of functional recovery. c-Jun, although not required for Schwann cell development, is therefore central to the reprogramming of myelin and non-myelin (Remak) Schwann cells to repair cells after injury. In future, the signalling that specifies this cell requires further analysis so that pharmacological tools that boost and maintain the repair Schwann cell phenotype can be developed.
Topics: Animals; Humans; Myelin Sheath; Nerve Regeneration; Nervous System Diseases; Schwann Cells
PubMed: 26864683
DOI: 10.1113/JP270874 -
Neuron Nov 2022Remyelination, the myelin regenerative response that follows demyelination, restores saltatory conduction and function and sustains axon health. Its declining efficiency... (Review)
Review
Remyelination, the myelin regenerative response that follows demyelination, restores saltatory conduction and function and sustains axon health. Its declining efficiency with disease progression in the chronic autoimmune disease multiple sclerosis (MS) contributes to the currently untreatable progressive phase of the disease. Although some of the bona fide myelin regenerative medicine clinical trials have succeeded in demonstrating proof-of-principle, none of these compounds have yet proceeded toward approval. There therefore remains a need to increase our understanding of the fundamental biology of remyelination so that existing targets can be refined and new ones discovered. Here, we review the role of inflammation, in particular innate immunity, in remyelination, describing its many and complex facets and discussing how our evolving understanding can be harnessed to translational goals.
Topics: Humans; Remyelination; Oligodendroglia; Myelin Sheath; Multiple Sclerosis; Inflammation
PubMed: 36228613
DOI: 10.1016/j.neuron.2022.09.023 -
Sleep Medicine Clinics Sep 2015Restless leg syndrome/Willis-Ekbom disease has brain iron deficiency that produces excessive dopamine and known genetic risks, some of which contribute to the brain iron... (Review)
Review
Restless leg syndrome/Willis-Ekbom disease has brain iron deficiency that produces excessive dopamine and known genetic risks, some of which contribute to the brain iron deficiency. Dopamine treatments work temporarily but may eventually produce further postsynaptic down-regulation and worse restless leg syndrome. This article includes sections focused on pathophysiologic findings from each of these areas: genetics, cortical-spinal excitability, and iron and dopamine.
Topics: Brain; Dopamine; Humans; Iron; Myelin Sheath; Restless Legs Syndrome
PubMed: 26329430
DOI: 10.1016/j.jsmc.2015.05.022 -
Physiological Reviews Apr 2001Oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), and astrocytes constitute macroglia. This review deals with the recent progress related... (Review)
Review
Oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), and astrocytes constitute macroglia. This review deals with the recent progress related to the origin and differentiation of the oligodendrocytes, their relationships to other neural cells, and functional neuroglial interactions under physiological conditions and in demyelinating diseases. One of the problems in studies of the CNS is to find components, i.e., markers, for the identification of the different cells, in intact tissues or cultures. In recent years, specific biochemical, immunological, and molecular markers have been identified. Many components specific to differentiating oligodendrocytes and to myelin are now available to aid their study. Transgenic mice and spontaneous mutants have led to a better understanding of the targets of specific dys- or demyelinating diseases. The best examples are the studies concerning the effects of the mutations affecting the most abundant protein in the central nervous myelin, the proteolipid protein, which lead to dysmyelinating diseases in animals and human (jimpy mutation and Pelizaeus-Merzbacher disease or spastic paraplegia, respectively). Oligodendrocytes, as astrocytes, are able to respond to changes in the cellular and extracellular environment, possibly in relation to a glial network. There is also a remarkable plasticity of the oligodendrocyte lineage, even in the adult with a certain potentiality for myelin repair after experimental demyelination or human diseases.
Topics: Animals; Brain Neoplasms; Central Nervous System; Demyelinating Diseases; Humans; Mammals; Myelin Proteins; Myelin Sheath; Neuroglia; Oligodendroglia; Oligodendroglioma
PubMed: 11274346
DOI: 10.1152/physrev.2001.81.2.871 -
Acta Neuropathologica Communications Mar 2018Alzheimer's disease (AD) is conceptualized as a progressive consequence of two hallmark pathological changes in grey matter: extracellular amyloid plaques and... (Review)
Review
Alzheimer's disease (AD) is conceptualized as a progressive consequence of two hallmark pathological changes in grey matter: extracellular amyloid plaques and neurofibrillary tangles. However, over the past several years, neuroimaging studies have implicated micro- and macrostructural abnormalities in white matter in the risk and progression of AD, suggesting that in addition to the neuronal pathology characteristic of the disease, white matter degeneration and demyelination may be also important pathophysiological features. Here we review the evidence for white matter abnormalities in AD with a focus on myelin and oligodendrocytes, the only source of myelination in the central nervous system, and discuss the relationship between white matter changes and the hallmarks of Alzheimer's disease. We review several mechanisms such as ischemia, oxidative stress, excitotoxicity, iron overload, Aβ toxicity and tauopathy, which could affect oligodendrocytes. We conclude that white matter abnormalities, and in particular myelin and oligodendrocytes, could be mechanistically important in AD pathology and could be potential treatment targets.
Topics: Alzheimer Disease; Animals; Humans; Myelin Sheath; White Matter
PubMed: 29499767
DOI: 10.1186/s40478-018-0515-3