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Journal of Neurochemistry Aug 2022Oligodendrocytes are the glial cells responsible for the formation of myelin around axons of the central nervous system (CNS). Myelin is an insulating layer that allows... (Review)
Review
Oligodendrocytes are the glial cells responsible for the formation of myelin around axons of the central nervous system (CNS). Myelin is an insulating layer that allows electrical impulses to transmit quickly and efficiently along neurons. If myelin is damaged, as in chronic demyelinating disorders such as multiple sclerosis (MS), these impulses slow down. Remyelination by oligodendrocytes is often ineffective in MS, in part because of the failure of oligodendrocyte precursor cells (OPCs) to differentiate into mature, myelinating oligodendrocytes. The process of oligodendrocyte differentiation is tightly controlled by several regulatory networks involving transcription factors, intracellular signaling pathways, and extrinsic cues. Understanding the factors that regulate oligodendrocyte development is essential for the discovery of new therapeutic strategies capable of enhancing remyelination. Over the past decade, microRNAs (miRNAs) have emerged as key regulators of oligodendrocyte development, exerting effects on cell specification, proliferation, differentiation, and myelination. This article will review the role of miRNAs on oligodendrocyte biology and discuss their potential as promising therapeutic tools for remyelination.
Topics: Cell Differentiation; Humans; MicroRNAs; Multiple Sclerosis; Myelin Sheath; Oligodendrocyte Precursor Cells; Oligodendroglia; Remyelination
PubMed: 35536759
DOI: 10.1111/jnc.15618 -
ASN Neuro 2023Myelination contributes not only to the rapid nerve conduction but also to axonal insulation and protection. In the central nervous system (CNS), the initial myelination... (Review)
Review
Myelination contributes not only to the rapid nerve conduction but also to axonal insulation and protection. In the central nervous system (CNS), the initial myelination features a multistep process where oligodendrocyte precursor cells undergo proliferation and migration before differentiating into mature oligodendrocytes. Mature oligodendrocytes then extend processes and wrap around axons to form the multilayered myelin sheath. These steps are tightly regulated by various cellular and molecular mechanisms, such as transcription factors (Olig family, Sox family), growth factors (PDGF, BDNF, FGF-2, IGF), chemokines/cytokines (TGF-β, IL-1β, TNFα, IL-6, IFN-γ), hormones (T3), axonal signals (PSA-NCAM, L1-CAM, LINGO-1, neural activity), and intracellular signaling pathways (Wnt/β-catenin, PI3 K/AKT/mTOR, ERK/MAPK). However, the fundamental mechanisms for initial myelination are yet to be fully elucidated. Identifying pivotal mechanisms for myelination onset, development, and repair will become the focus of future studies. This review focuses on the current understanding of how CNS myelination is initiated and also the regulatory mechanisms underlying the process.
Topics: Central Nervous System; Myelin Sheath; Axons; Oligodendroglia; Signal Transduction
PubMed: 36974372
DOI: 10.1177/17590914231163039 -
Progress in Neurobiology Jul 2023Oligodendrocytes are responsible for myelinating central nervous system (CNS) axons and rapid electrical transmission through saltatory conduction of action potentials.... (Review)
Review
Oligodendrocytes are responsible for myelinating central nervous system (CNS) axons and rapid electrical transmission through saltatory conduction of action potentials. Myelination and myelin repair rely partially on oligodendrogenesis, which comprises oligodendrocyte precursor cell (OPC) migration, maturation, and differentiation into oligodendrocytes (OL). In multiple sclerosis (MS), demyelination occurs due to an inflammatory cascade with auto-reactive T-cells. When oligodendrogenesis fails, remyelination becomes aberrant and conduction impairments are no longer restored. Although current disease modifying therapies have achieved results in modulating the faulty immune response, disease progression continues because of chronic inflammation, neurodegeneration, and failure of remyelination. Therapies have been tried to promote remyelination. Modulation of neuronal activity seems to be a very promising strategy in preclinical studies. Additionally, studies in people with MS (pwMS) have shown symptom improvement following non-invasive brain stimulation. (NIBS) techniques. The aforementioned mechanisms are yet unknown and probably involve both the activation of neurons and glial cells. Noting neuronal activity contributes to myelin plasticity and that NIBS modulates neuronal activity; we argue that NIBS is a promising research horizon for demyelinating diseases. We review the hypothesized pathways through which NIBS may affect both neuronal activity in the CNS and how the resulting activity can affect oligodendrogenesis and myelination.
Topics: Humans; Remyelination; Myelin Sheath; Oligodendroglia; Multiple Sclerosis; Cell Differentiation
PubMed: 37127087
DOI: 10.1016/j.pneurobio.2023.102459 -
Current Opinion in Neurobiology Dec 2017Myelin increases the speed and efficiency of action potential propagation. Yet, not all axons are myelinated and some axons are discontinuously myelinated, prompting the... (Review)
Review
Myelin increases the speed and efficiency of action potential propagation. Yet, not all axons are myelinated and some axons are discontinuously myelinated, prompting the question of how myelinating glia select axons for myelination. Whereas myelination by Schwann cells depends on axonal induction, oligodendrocytes can form myelin membrane in the absence of axons. However, oligodendrocytes alone cannot architect the complex myelination patterns of the central nervous system and recent advances have implicated axonal signaling in this process. This review considers how oligodendrocytes and their precursors could be influenced by inductive, attractive, permissive, repulsive, and preventative cues, and discusses recent evidence identifying synaptic activity and membrane-bound adhesion molecules as such cues directing axon selection.
Topics: Animals; Axons; Central Nervous System; Humans; Myelin Sheath; Neural Stem Cells; Oligodendroglia
PubMed: 28709021
DOI: 10.1016/j.conb.2017.06.005 -
Current Opinion in Neurobiology Dec 2017Myelin sheaths in the vertebrate nervous system enable faster impulse propagation, while myelinating glia provide vital support to axons. Once considered a static... (Review)
Review
Myelin sheaths in the vertebrate nervous system enable faster impulse propagation, while myelinating glia provide vital support to axons. Once considered a static insulator, converging evidence now suggests that myelin in the central nervous system can be dynamically regulated by neuronal activity and continues to participate in nervous system plasticity beyond development. While the link between experience and myelination gains increased recognition, it is still unclear what role such adaptive myelination plays in facilitating and shaping behaviour. Additionally, fundamental mechanisms and principles underlying myelin remodelling remain poorly understood. In this review, we will discuss new insights into the link between myelin plasticity and behaviour, as well as mechanistic aspects of myelin remodelling that may help to elucidate this intriguing process.
Topics: Animals; Brain; Humans; Learning; Myelin Sheath; Neuronal Plasticity; White Matter
PubMed: 29054040
DOI: 10.1016/j.conb.2017.09.014 -
Neuroscience Letters Jan 2020The central nervous system maintains the potential for molecular and cellular plasticity throughout life. This flexibility underlies fundamental features of neural... (Review)
Review
The central nervous system maintains the potential for molecular and cellular plasticity throughout life. This flexibility underlies fundamental features of neural circuitry including the brain's ability to sense, store, and properly adapt to everchanging external stimuli on time scales from seconds to years. Evidence for most forms of plasticity are centered around changes in neuronal structure and synaptic strength, however recent data suggests that myelinating oligodendrocytes exhibit certain forms of plasticity in the adult. This plasticity ranges from the generation of entirely new myelinating cells to more subtle changes in myelin sheath length, thickness, and distribution along axons. The extent to which these changes dynamically modify axonal function and neural circuitry and whether they are directly related to mechanisms of learning and memory remains an open question. Here we describe different forms of myelin plasticity, highlight some recent evidence for changes in myelination throughout life, and discuss how defects in these forms of plasticity could be associated with cognitive decline in aging.
Topics: Aging; Animals; Cognitive Dysfunction; Humans; Myelin Sheath; Neuronal Plasticity; Oligodendroglia
PubMed: 31765728
DOI: 10.1016/j.neulet.2019.134645 -
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 -
Glia Jan 2018In the central nervous system, oligodendrocyte precursor cells are exclusive in their potential to differentiate into myelinating oligodendrocytes. Oligodendrocyte... (Review)
Review
In the central nervous system, oligodendrocyte precursor cells are exclusive in their potential to differentiate into myelinating oligodendrocytes. Oligodendrocyte precursor cells migrate within the parenchyma and extend cell membrane protrusions that ultimately evolve into myelinating sheaths able to wrap neuronal axons and significantly increase their electrical conductivity. The subcellular force generating mechanisms driving morphological and functional transformations during oligodendrocyte differentiation and myelination remain elusive. In this review, we highlight the mechanical processes governing oligodendrocyte plasticity in a dynamic interaction with the extracellular matrix.
Topics: Animals; Cell Differentiation; Cell Plasticity; Central Nervous System; Extracellular Matrix; Humans; Myelin Sheath; Oligodendroglia
PubMed: 28940651
DOI: 10.1002/glia.23206 -
Glia Dec 2022Myelin is essential to nervous system function, playing roles in saltatory conduction and trophic support. Oligodendrocytes (OLs) and Schwann cells (SCs) form myelin in... (Review)
Review
Myelin is essential to nervous system function, playing roles in saltatory conduction and trophic support. Oligodendrocytes (OLs) and Schwann cells (SCs) form myelin in the central and peripheral nervous systems respectively and follow different developmental paths. OLs are neural stem-cell derived and follow an intrinsic developmental program resulting in a largely irreversible differentiation state. During embryonic development, OL precursor cells (OPCs) are produced in distinct waves originating from different locations in the central nervous system, with a subset developing into myelinating OLs. OPCs remain evenly distributed throughout life, providing a population of responsive, multifunctional cells with the capacity to remyelinate after injury. SCs derive from the neural crest, are highly dependent on extrinsic signals, and have plastic differentiation states. SC precursors (SCPs) are produced in early embryonic nerve structures and differentiate into multipotent immature SCs (iSCs), which initiate radial sorting and differentiate into myelinating and non-myelinating SCs. Differentiated SCs retain the capacity to radically change phenotypes in response to external signals, including becoming repair SCs, which drive peripheral regeneration. While several transcription factors and myelin components are common between OLs and SCs, their differentiation mechanisms are highly distinct, owing to their unique lineages and their respective environments. In addition, both OLs and SCs respond to neuronal activity and regulate nervous system output in reciprocal manners, possibly through different pathways. Here, we outline their basic developmental programs, mechanisms regulating their differentiation, and recent advances in the field.
Topics: Female; Humans; Myelin Sheath; Neuroglia; Peripheral Nervous System; Pregnancy; Schwann Cells; Transcription Factors
PubMed: 35785432
DOI: 10.1002/glia.24238 -
Yakugaku Zasshi : Journal of the... 2022Myelin is a multilamellar membrane structure formed by oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS). It... (Review)
Review
Myelin is a multilamellar membrane structure formed by oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS). It has been recognized as an insulator that is essential for the rapid and efficient propagation of action potentials by saltatory conduction. However, recently many studies have shown that myelin and myelin-forming cells interact with axons and regulate the nervous system far more actively than previously thought. For example, myelination changes axons dynamically and divides them into four distinct functional domains: node of Ranvier, paranode, juxtaparanode, and internode. Voltage-gated Na channels are clustered at the node, while K channels are at the juxtaparanode, and segregation of these channels by paranodal axoglial junction is necessary for proper axonal function. My research experience began at the neurology ward of the Niigata University Medical Hospital, where I saw a patient with peripheral neuropathy of unknown etiology more than 37 years ago. In the patient's serum, we found an autoantibody against a glycolipid enriched in the PNS. Since then, I have been interested in myelin because of its beautiful structure and unique roles in the nervous system. In this review, our recent studies related to CNS and PNS myelin are presented.
Topics: Autoantibodies; Axons; Central Nervous System; Humans; Myelin Sheath; Ranvier's Nodes; Schwann Cells
PubMed: 35908945
DOI: 10.1248/yakushi.21-00224