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Trends in Neurosciences Apr 2019Myelin is a multilayer lipid membrane structure that wraps and insulates axons, allowing for the efficient propagation of action potentials. During developmental... (Review)
Review
Myelin is a multilayer lipid membrane structure that wraps and insulates axons, allowing for the efficient propagation of action potentials. During developmental myelination of the central nervous system (CNS), oligodendrocyte progenitor cells (OPCs) proliferate and migrate to their final destination, where they terminally differentiate into mature oligodendrocytes and myelinate axons. Lineage progression and terminal differentiation of oligodendrocyte lineage cells are under tight transcriptional and post-transcriptional control. The characterization of several recently identified regulatory factors that govern these processes, which are the focus of this review, has greatly increased our understanding of oligodendrocyte development and function. These insights are critical to facilitate efforts to enhance OPC differentiation in neurological disorders that disrupt CNS myelin.
Topics: Animals; Cell Differentiation; Humans; Oligodendroglia
PubMed: 30770136
DOI: 10.1016/j.tins.2019.01.002 -
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 -
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 -
Nature Reviews. Neuroscience Dec 2020Throughout our lifespan, new sensory experiences and learning continually shape our neuronal circuits to form new memories. Plasticity at the level of synapses has been... (Review)
Review
Throughout our lifespan, new sensory experiences and learning continually shape our neuronal circuits to form new memories. Plasticity at the level of synapses has been recognized and studied for decades, but recent work has revealed an additional form of plasticity - affecting oligodendrocytes and the myelin sheaths they produce - that plays a crucial role in learning and memory. In this Review, we summarize recent work characterizing plasticity in the oligodendrocyte lineage following sensory experience and learning, the physiological and behavioural consequences of manipulating that plasticity, and the evidence for oligodendrocyte and myelin dysfunction in neurodevelopmental disorders with cognitive symptoms. We also discuss the limitations of existing approaches and the conceptual and technical advances that are needed to move forward this rapidly developing field.
Topics: Animals; Demyelinating Diseases; Humans; Learning; Memory; Myelin Sheath; Neuronal Plasticity; Oligodendroglia; Synapses
PubMed: 33046886
DOI: 10.1038/s41583-020-00379-8 -
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 -
Trends in Neurosciences Jul 2023Adult oligodendrocyte precursor cells (aOPCs), transformed from fetal OPCs, are idiosyncratic neuroglia of the central nervous system (CNS) that are distinct in many... (Review)
Review
Adult oligodendrocyte precursor cells (aOPCs), transformed from fetal OPCs, are idiosyncratic neuroglia of the central nervous system (CNS) that are distinct in many ways from other glial cells. OPCs have been classically studied in the context of their remyelinating capacity. Recent studies, however, revealed that aOPCs not only contribute to post-lesional remyelination but also play diverse crucial roles in multiple neurological diseases. In this review we briefly present the physiology of aOPCs and summarize current knowledge of the beneficial and detrimental roles of aOPCs in different CNS diseases. We discuss unique features of aOPC death, reactivity, and changes during senescence, as well as aOPC interactions with other glial cells and pathological remodeling during disease. Finally, we outline future perspectives for the study of aOPCs in brain pathologies which may instigate the development of aOPC-targeting therapeutic strategies.
Topics: Oligodendrocyte Precursor Cells; Central Nervous System; Neuroglia; Remyelination; Oligodendroglia; Cell Differentiation; Myelin Sheath
PubMed: 37183154
DOI: 10.1016/j.tins.2023.04.003 -
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 -
Nature Reviews. Neuroscience Nov 2017Although the core concept of remyelination - based on the activation, migration, proliferation and differentiation of CNS progenitors - has not changed over the past 20... (Review)
Review
Although the core concept of remyelination - based on the activation, migration, proliferation and differentiation of CNS progenitors - has not changed over the past 20 years, our understanding of the detailed mechanisms that underlie this process has developed considerably. We can now decorate the central events of remyelination with a host of pathways, molecules, mediators and cells, revealing a complex and precisely orchestrated process. These advances have led to recent drug-based and cell-based clinical trials for myelin diseases and have opened up hitherto unrecognized opportunities for drug-based approaches to therapeutically enhance remyelination.
Topics: Animals; Cell Differentiation; Central Nervous System; Demyelinating Diseases; Humans; Myelin Sheath; Nerve Regeneration; Oligodendroglia
PubMed: 29142295
DOI: 10.1038/nrn.2017.136 -
Nature Reviews. Neuroscience Dec 2023Experience sculpts brain structure and function. Activity-dependent modulation of the myelinated infrastructure of the nervous system has emerged as a dimension of... (Review)
Review
Experience sculpts brain structure and function. Activity-dependent modulation of the myelinated infrastructure of the nervous system has emerged as a dimension of adaptive change during childhood development and in adulthood. Myelination is a richly dynamic process, with neuronal activity regulating oligodendrocyte precursor cell proliferation, oligodendrogenesis and myelin structural changes in some axonal subtypes and in some regions of the nervous system. This myelin plasticity and consequent changes to conduction velocity and circuit dynamics can powerfully influence neurological functions, including learning and memory. Conversely, disruption of the mechanisms mediating adaptive myelination can contribute to cognitive impairment. The robust effects of neuronal activity on normal oligodendroglial precursor cells, a putative cellular origin for many forms of glioma, indicates that dysregulated or 'hijacked' mechanisms of myelin plasticity could similarly promote growth in this devastating group of brain cancers. Indeed, neuronal activity promotes the pathogenesis of many forms of glioma in preclinical models through activity-regulated paracrine factors and direct neuron-to-glioma synapses. This synaptic integration of glioma into neural circuits is central to tumour growth and invasion. Thus, not only do neuron-oligodendroglial interactions modulate neural circuit structure and function in the healthy brain, but neuron-glioma interactions also have important roles in the pathogenesis of glial malignancies.
Topics: Humans; Neurons; Oligodendroglia; Myelin Sheath; Neuroglia; Glioma
PubMed: 37857838
DOI: 10.1038/s41583-023-00744-3 -
Nature Neuroscience Mar 2019Investigating human oligodendrogenesis and the interaction of oligodendrocytes with neurons and astrocytes would accelerate our understanding of the mechanisms...
Investigating human oligodendrogenesis and the interaction of oligodendrocytes with neurons and astrocytes would accelerate our understanding of the mechanisms underlying white matter disorders. However, this is challenging because of the limited accessibility of functional human brain tissue. Here, we developed a new differentiation method of human induced pluripotent stem cells to generate three-dimensional brain organoids that contain oligodendrocytes as well as neurons and astrocytes, called human oligodendrocyte spheroids. We found that oligodendrocyte lineage cells derived in human oligodendrocyte spheroids transitioned through developmental stages similar to primary human oligodendrocytes and that the migration of oligodendrocyte lineage cells and their susceptibility to lysolecithin exposure could be captured by live imaging. Moreover, their morphology changed as they matured over time in vitro and started myelinating neurons. We anticipate that this method can be used to study oligodendrocyte development, myelination, and interactions with other major cell types in the CNS.
Topics: Astrocytes; Cell Culture Techniques; Cell Differentiation; Cell Line; Cell Lineage; Humans; Induced Pluripotent Stem Cells; Neurons; Oligodendroglia; Spheroids, Cellular; Transcriptome
PubMed: 30692691
DOI: 10.1038/s41593-018-0316-9