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Acta Neuropathologica Feb 2022It is the centenary of the discovery of oligodendrocytes and we are increasingly aware of their importance in the functioning of the brain in development, adult... (Review)
Review
It is the centenary of the discovery of oligodendrocytes and we are increasingly aware of their importance in the functioning of the brain in development, adult learning, normal ageing and in disease across the life course, even in those diseases classically thought of as neuronal. This has sparked more interest in oligodendroglia for potential therapeutics for many neurodegenerative/neurodevelopmental diseases due to their more tractable nature as a renewable cell in the central nervous system. However, oligodendroglia are not all the same. Even from the first description, differences in morphology were described between the cells. With advancing techniques to describe these differences in human tissue, the complexity of oligodendroglia is being discovered, indicating apparent functional differences which may be of critical importance in determining vulnerability and response to disease, and targeting of potential therapeutics. It is timely to review the progress we have made in discovering and understanding oligodendroglial heterogeneity in health and neuropathology.
Topics: Central Nervous System; Humans; Oligodendroglia
PubMed: 34860266
DOI: 10.1007/s00401-021-02390-4 -
Advances in Experimental Medicine and... 2019Oligodendrocytes are the myelinating cells of the CNS, producing the insulating myelin sheath that facilitates rapid electrical conduction of axonal action potentials.... (Review)
Review
Oligodendrocytes are the myelinating cells of the CNS, producing the insulating myelin sheath that facilitates rapid electrical conduction of axonal action potentials. Oligodendrocytes arise from oligodendrocyte progenitor cells (OPCs) under the control of multiple factors, including neurotransmitters and other neuron-derived factors. A significant population of OPCs persists in the adult CNS, where they are often referred to as NG2-glia, because they are identified by their expression of the NG2 chondroitin sulphate proteoglycan (CSPG4). In the adult brain, the primary function of NG2-glia is the life-long generation of oligodendrocytes to replace myelin lost through natural 'wear and tear' and pathology, as well as to provide new oligodendrocytes to myelinate new connections formed in response to new life experiences. NG2-glia contact synapses and respond to neurotransmitters and potassium released during neuronal transmission; to this end, NG2-glia (OPCs) express multiple neurotransmitter receptors and ion channels, with prominent roles being identified for glutamatergic signalling and potassium channels in oligodendrocyte differentiation. Myelinating oligodendrocytes also express a wide range of neurotransmitter receptors and ion channels, together with transporters and gap junctions; together, these have critical functions in cellular ion and water homeostasis, as well as metabolism, which is essential for maintaining myelin and axon integrity. An overriding theme is that oligodendrocyte function and myelination is not only essential for rapid axonal conduction, but is essential for learning and the long-term integrity of axons and neurones. Hence, myelination underpins cognitive function and the massive computing power of the human brain and myelin loss has devastating effects on CNS function. This chapter focuses on normal oligodendrocyte physiology.
Topics: Axons; Humans; Myelin Sheath; Neural Stem Cells; Neurons; Oligodendroglia
PubMed: 31583586
DOI: 10.1007/978-981-13-9913-8_5 -
Neuropathology : Official Journal of... Oct 2017Oligodendroglia are cells responsible for creating myelin sheaths for axons in the CNS. However, pathologies of oligodendroglia other than demyelination are not well... (Review)
Review
Oligodendroglia are cells responsible for creating myelin sheaths for axons in the CNS. However, pathologies of oligodendroglia other than demyelination are not well understood due to the lack of adequate methods of characterizing pathological conditions affecting oligodendroglia in human tissue. This review discusses three major topics with the aim of clarifying some of the controversies in the study of oligodendroglia. The oligodendroglioma, a relatively indolent form of diffuse gliomas thought to originate in oligodendrocytes, has never demonstrated myelin formation on electron microscopy nor shown a constant expression of myelin-related proteins. Oligodendrogliomas instead share an immune phenotype with oligodendrocyte progenitor cells (OPCs). Another type of cell that resembles OPCs are oligodendroglia-like cells (OLCs), which occur in many types of low-grade tumors and focal cortical dysplasia. In neurodegenerative disorders, oligodendroglia can be a target of abnormal aggregations of proteins such as tau. Tau-positive oligodendroglial inclusions in progressive supranuclear palsy and corticobasal generation differ from each other morphologically, ultrastructurally and biochemically, suggesting disparate underlying pathological processes despite significant overlapping of the clinical manifestations. To promote the study of oligodendroglia, novel methods for detecting OLCs in situ are urgently required.
Topics: Animals; Humans; Oligodendroglia
PubMed: 28548216
DOI: 10.1111/neup.12389 -
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 -
Molecular Psychiatry Jan 2021Depression is a common mental illness, affecting more than 300 million people worldwide. Decades of investigation have yielded symptomatic therapies for this disabling... (Review)
Review
Depression is a common mental illness, affecting more than 300 million people worldwide. Decades of investigation have yielded symptomatic therapies for this disabling condition but have not led to a consensus about its pathogenesis. There are data to support several different theories of causation, including the monoamine hypothesis, hypothalamic-pituitary-adrenal axis changes, inflammation and immune system alterations, abnormalities of neurogenesis and a conducive environmental milieu. Research in these areas and others has greatly advanced the current understanding of depression; however, there are other, less widely known theories of pathogenesis. Oligodendrocyte lineage cells, including oligodendrocyte progenitor cells and mature oligodendrocytes, have numerous important functions, which include forming myelin sheaths that enwrap central nervous system axons, supporting axons metabolically, and mediating certain forms of neuroplasticity. These specialized glial cells have been implicated in psychiatric disorders such as depression. In this review, we summarize recent findings that shed light on how oligodendrocyte lineage cells might participate in the pathogenesis of depression, and we discuss new approaches for targeting these cells as a novel strategy to treat depression.
Topics: Cell Lineage; Depression; Humans; Myelin Sheath; Oligodendroglia
PubMed: 33144710
DOI: 10.1038/s41380-020-00930-0 -
Neuron Apr 2021Myelin, multilayered lipid-rich membrane extensions formed by oligodendrocytes around neuronal axons, is essential for fast and efficient action potential propagation in... (Review)
Review
Myelin, multilayered lipid-rich membrane extensions formed by oligodendrocytes around neuronal axons, is essential for fast and efficient action potential propagation in the central nervous system. Initially thought to be a static and immutable process, myelination is now appreciated to be a dynamic process capable of responding to and modulating neuronal function throughout life. While the importance of this type of plasticity, called adaptive myelination, is now well accepted, we are only beginning to understand the underlying cellular and molecular mechanisms by which neurons communicate experience-driven circuit activation to oligodendroglia and precisely how changes in oligodendrocytes and their myelin refine neuronal function. Here, we review recent findings addressing this reciprocal relationship in which neurons alter oligodendroglial form and oligodendrocytes conversely modulate neuronal function.
Topics: Animals; Brain; Humans; Myelin Sheath; Neuronal Plasticity; Neurons; Oligodendroglia
PubMed: 33621477
DOI: 10.1016/j.neuron.2021.02.003 -
Current Pharmaceutical Design 2016Oligodendrocytes are the myelinating cells of the central nervous system that constitute about 5 to 10% of the total glial population. These cells are responsible for... (Review)
Review
Oligodendrocytes are the myelinating cells of the central nervous system that constitute about 5 to 10% of the total glial population. These cells are responsible for myelin sheath production, which is essential not only for the rapid and efficient conduction of the electrical impulses along the axons, but also for preserving axonal integrity. Oligodendrocytes arise from oligodendrocyte progenitor cells that proliferate and differentiate just before and after birth, under a highly-regulated program. Both oligodendrocytes and their precursors are very susceptible to injury by several mechanisms, including excitotoxic damage, oxidative stress and inflammatory events. In this review, we will cover not only several important aspects of oligodendrocyte development and regulatory mechanisms involved in this process, but also some of the most important pathways of injury associated to oligodendrogenesis. Moreover, we will also address some neurological disorders along life journey that present impairment in oligodendrocyte function and in myelination during neurodevelopment, such as periventricular leukomalacia, hypoxia/ischemia and hyperbilirubinemia that in turn can potentiate the emergence of neurological and neurodegenerative diseases like schizophrenia, multiple sclerosis and Alzheimer's disease.
Topics: Animals; Cell Communication; Cell Differentiation; Cell Lineage; Central Nervous System Diseases; Humans; Myelin Sheath; Nervous System; Neurons; Oligodendroglia
PubMed: 26635271
DOI: 10.2174/1381612822666151204000636 -
Science (New York, N.Y.) Oct 2014Myelin-forming oligodendrocytes (OLs) are formed continuously in the healthy adult brain. In this work, we study the function of these late-forming cells and the myelin...
Myelin-forming oligodendrocytes (OLs) are formed continuously in the healthy adult brain. In this work, we study the function of these late-forming cells and the myelin they produce. Learning a new motor skill (such as juggling) alters the structure of the brain's white matter, which contains many OLs, suggesting that late-born OLs might contribute to motor learning. Consistent with this idea, we show that production of newly formed OLs is briefly accelerated in mice that learn a new skill (running on a "complex wheel" with irregularly spaced rungs). By genetically manipulating the transcription factor myelin regulatory factor in OL precursors, we blocked production of new OLs during adulthood without affecting preexisting OLs or myelin. This prevented the mice from mastering the complex wheel. Thus, generation of new OLs and myelin is important for learning motor skills.
Topics: Animals; Brain; Cell Proliferation; Gene Deletion; Humans; Learning; Male; Mental Recall; Mice; Mice, Transgenic; Motor Skills; Myelin Sheath; Oligodendroglia; Synaptic Transmission; Transcription Factors
PubMed: 25324381
DOI: 10.1126/science.1254960 -
Journal of the Neurological Sciences Feb 1986During postnatal development of the higher vertebrate CNS, large populations of oligodendroglia are generated from precursor cells in a very dependable way. In adult... (Review)
Review
During postnatal development of the higher vertebrate CNS, large populations of oligodendroglia are generated from precursor cells in a very dependable way. In adult lesioned CNS tissues, local populations of oligodendroglia are replenished by proliferation of this replenishment varies from one species to another and also from one lesion type another. Studies on the developmental generation of oligodendroglia are reviewed here, delineating what is known of the early relationships between the CNS glial lineages and of what regulates this development. Contributions from recent cell biological work are considered against the background of morphological and radioautographic results. The quiescent condition of extremely slow turnover in the normal adult CNS is noted, and the dramatic effects of lesions on the neural cell environment are considered. Lesions can trigger proliferation at a much greater rate in the mature oligodendroglial population, as observed both in situ and in tissue culture; in addition to persisting stem cells, the mature cells participate in replenishing the local oligodendroglial population. This regeneration from cells already committed to the oligodendroglial lineage may minimise such disturbing effects of the lesion environment as might distort replenishment of the population from precursor cells.
Topics: Animals; Blood-Brain Barrier; Cell Differentiation; Cell Separation; Cell Survival; Cells, Cultured; Central Nervous System; Demyelinating Diseases; Galactosylceramides; Glial Fibrillary Acidic Protein; Glucose; Humans; Insulin; Mice; Mice, Neurologic Mutants; Mitosis; Myelin Basic Protein; Myelin Proteins; Myelin Sheath; Neuroglia; Oligodendroglia; Rats
PubMed: 2423650
DOI: 10.1016/0022-510x(86)90019-5 -
Neuroscience Letters Jun 2009Cell therapy appears as an exciting strategy for myelin repair in pathologies where oligodendrocytes are deficient or impaired, such as leucodystrophies and multiple... (Review)
Review
Cell therapy appears as an exciting strategy for myelin repair in pathologies where oligodendrocytes are deficient or impaired, such as leucodystrophies and multiple sclerosis. Many studies indicate that several types of rodent cells, including neural stem and progenitor cells, play a beneficial role after grafting and induce functional recovery in animal models of myelin disorders. However, the difficulties to commit human neural stem cells towards the oligodendroglial lineage have long hampered human cell-based therapy for these diseases. In this review, we present recent advances in the field and discuss the various strategies that helped overcome the challenge of human oligodendroglial differentiation.
Topics: Animals; Cell Differentiation; Demyelinating Diseases; Humans; Immunohistochemistry; Mice; Myelin Sheath; Oligodendroglia; Rats; Stem Cells
PubMed: 19429145
DOI: 10.1016/j.neulet.2008.09.086