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Archives of Pharmacal Research Sep 2020The central nervous system is simply divided into two distinct anatomical regions based on the color of tissues, i.e. the gray and white matter. The gray matter is... (Review)
Review
The central nervous system is simply divided into two distinct anatomical regions based on the color of tissues, i.e. the gray and white matter. The gray matter is composed of neuronal cell bodies, glial cells, dendrites, immune cells, and the vascular system, while the white matter is composed of concentrated myelinated axonal fibers extending from neuronal soma and glial cells, such as oligodendrocyte precursor cells (OPCs), oligodendrocytes, astrocytes, and microglia. As neuronal cell bodies are located in the gray matter, great attention has been focused mainly on the gray matter regarding the understanding of the functions of the brain throughout the neurophysiological areas, leading to a scenario in which the function of the white matter is relatively underestimated or has not received much attention. However, increasing evidence shows that the white matter plays highly significant and pivotal functions in the brain based on the fact that its abnormalities are associated with numerous neurological diseases. In this review, we will broadly discuss the pathways and functions of myelination, which is one of the main processes that modulate the functions of the white matter, as well as the manner in which its abnormalities are related to neurological disorders.
Topics: Animals; Astrocytes; Axons; Cell Differentiation; Disease Models, Animal; Humans; Microglia; Myelin Sheath; Nervous System Diseases; Neural Conduction; Neuronal Plasticity; Oligodendrocyte Precursor Cells; Oligodendroglia; White Matter
PubMed: 32975736
DOI: 10.1007/s12272-020-01270-x -
Developmental Neurobiology Nov 2021Oligodendrocytes, the myelinating cells of the central nervous system (CNS), develop from oligodendrocyte progenitor cells (OPCs) that must first migrate extensively... (Review)
Review
Oligodendrocytes, the myelinating cells of the central nervous system (CNS), develop from oligodendrocyte progenitor cells (OPCs) that must first migrate extensively throughout the developing brain and spinal cord. Specified at particular times from discrete regions in the developing CNS, OPCs are one of the most migratory of cell types and disperse rapidly. A variety of factors act on OPCs to trigger intracellular changes that regulate their migration. We will discuss factors that act as long-range guidance cues, those that act to regulate cellular motility, and those that are critical in determining the final positioning of OPCs. In addition, recent evidence has identified the vasculature as the physical substrate used by OPCs for their migration. Several new findings relating to this oligodendroglial-vascular signaling axis reveal new insight on the relationship between OPCs and blood vessels in the developing and adult brain.
Topics: Cell Differentiation; Central Nervous System; Oligodendrocyte Precursor Cells; Oligodendroglia; Spinal Cord
PubMed: 34643996
DOI: 10.1002/dneu.22856 -
Glia Nov 2019Myelination is an evolutionary recent differentiation program that has been independently acquired in vertebrates by Schwann cells in the peripheral nervous system and... (Review)
Review
Myelination is an evolutionary recent differentiation program that has been independently acquired in vertebrates by Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. Therefore, it is not surprising that regulating transcription factors differ substantially between both cell types. However, overall principles are similar as transcriptional control in Schwann cells and oligodendrocytes combines lineage determining and stage-specific factors in complex regulatory networks. Myelination does not only occur during development, but also as remyelination in the adult. In line with the different conditions during developmental myelination and remyelination and the distinctive properties of Schwann cells and oligodendrocytes, transcriptional regulation of remyelination exhibits unique features and differs between the two cell types. This review gives an overview of the current state in the field.
Topics: Animals; Cell Differentiation; Demyelinating Diseases; Humans; Myelin Sheath; Oligodendroglia; Remyelination; Schwann Cells
PubMed: 31038810
DOI: 10.1002/glia.23636 -
Seminars in Cell & Developmental Biology Aug 2021The past decade has seen an important revision of the traditional concept of the role and function of glial cells. From "passive support" for neurons, oligodendrocyte... (Review)
Review
The past decade has seen an important revision of the traditional concept of the role and function of glial cells. From "passive support" for neurons, oligodendrocyte lineage cells are now recognized as metabolic exchangers with neurons, a cellular interface with blood vessels and responders to gut-derived metabolites or changes in the social environment. In the developing brain, the differentiation of neonatal oligodendrocyte progenitors (nOPCs) is required for normal brain function. In adulthood, the differentiation of adult OPCs (aOPCs) serves an important role in learning, behavioral adaptation and response to myelin injury. Here, we propose the concept of OPCs as environmental biosensors, which "sense" chemical and physical stimuli over time and adjust to the new challenges by modifying their epigenome and consequent transcriptome. Because epigenetics defines the ability of the cell to "adapt" gene expression to changes in the environment, we propose a model of OPC differentiation resulting from time-dependent changes of the epigenomic landscape in response to declining mitogens, raising hormone levels, neuronal activity, changes in space constraints or stiffness of the extracellular matrix. We propose that the intrinsically different functional properties of aOPCs compared to nOPCs result from the accrual of "epigenetic memories" of distinct events, which are "recorded" in the nuclei of OPCs as histone and DNA marks, defining a "unique epigenomic landscape" over time.
Topics: Biosensing Techniques; Epigenesis, Genetic; Humans; Oligodendroglia; Stem Cells
PubMed: 33092959
DOI: 10.1016/j.semcdb.2020.09.012 -
Trends in Neurosciences Aug 2020Remyelination is the regeneration of myelin sheaths following demyelination. This regenerative process is critical for the re-establishment of axonal conduction velocity... (Review)
Review
Remyelination is the regeneration of myelin sheaths following demyelination. This regenerative process is critical for the re-establishment of axonal conduction velocity and metabolic support to the axons. Successful remyelination in the CNS generally depends on the activation, proliferation, and differentiation of oligodendrocyte progenitor cells (OPCs). However, other cell types play critical roles in establishing where a lesion is conducive for regeneration. In the last few years, several studies have described beneficial and detrimental roles played by astrocytes in remyelination. This review will discuss recent developments in the concept of astrocyte reactivity, what is known about the astrocytic contribution to remyelination, and highlight future avenues of investigation.
Topics: Astrocytes; Cell Differentiation; Demyelinating Diseases; Humans; Myelin Sheath; Oligodendroglia; Remyelination
PubMed: 32620289
DOI: 10.1016/j.tins.2020.05.006 -
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 -
The Neuroscientist : a Review Journal... Feb 2020Oligodendrocytes generate myelin sheaths to promote rapid neurotransmission in the central nervous system (CNS). During brain development, oligodendrocyte precursor... (Review)
Review
Oligodendrocytes generate myelin sheaths to promote rapid neurotransmission in the central nervous system (CNS). During brain development, oligodendrocyte precursor cells (OPCs) are generated in the medial ganglionic eminence, lateral ganglionic eminence, and dorsal pallium. OPCs proliferate and migrate throughout the CNS at the embryonic stage. After birth, OPCs differentiate into mature oligodendrocytes, which then insulate axons. Oligodendrocyte development is regulated by the extrinsic environment including neurons, astrocytes, and immune cells. During brain development, B lymphocytes are present in the meningeal space, and are involved in oligodendrocyte development by promoting OPC proliferation. T lymphocytes mediate oligodendrocyte development during the remyelination process. Moreover, a subset of microglia contributes to oligodendrocyte development during the neonatal periods. Therefore, the immune system, especially lymphocytes and microglia, contribute to oligodendrocyte development during brain development and remyelination.
Topics: Animals; Axons; Cell Differentiation; Humans; Lymphocytes; Myelin Sheath; Neurons; Oligodendroglia
PubMed: 30845892
DOI: 10.1177/1073858419834221 -
International Journal of Molecular... Oct 2021Autism spectrum disorder (ASD) is an umbrella term encompassing several neurodevelopmental disorders such as Asperger syndrome or autism. It is characterised by the... (Review)
Review
Autism spectrum disorder (ASD) is an umbrella term encompassing several neurodevelopmental disorders such as Asperger syndrome or autism. It is characterised by the occurrence of distinct deficits in social behaviour and communication and repetitive patterns of behaviour. The symptoms may be of different intensity and may vary in types. Risk factors for ASD include disturbed brain homeostasis, genetic predispositions, or inflammation during the prenatal period caused by viruses or bacteria. The number of diagnosed cases is growing, but the main cause and mechanism leading to ASD is still uncertain. Recent findings from animal models and human cases highlight the contribution of glia to the ASD pathophysiology. It is known that glia cells are not only "gluing" neurons together but are key players participating in different processes crucial for proper brain functioning, including neurogenesis, synaptogenesis, inflammation, myelination, proper glutamate processing and many others. Despite the prerequisites for the involvement of glia in the processes related to the onset of autism, there are far too little data regarding the engagement of these cells in the development of ASD.
Topics: Animals; Astrocytes; Autism Spectrum Disorder; Behavior, Animal; Calcium Signaling; Cell Shape; Disease Models, Animal; Female; Humans; Male; Microglia; Models, Neurological; Oligodendroglia; Sex Factors; Social Skills
PubMed: 34768975
DOI: 10.3390/ijms222111544 -
Journal of Neuroendocrinology Jul 2022Demyelination results from the pathological loss of myelin and is a hallmark of many neurodegenerative diseases. Despite the prevalence of demyelinating diseases, there... (Review)
Review
Demyelination results from the pathological loss of myelin and is a hallmark of many neurodegenerative diseases. Despite the prevalence of demyelinating diseases, there are no disease modifying therapies that prevent the loss of myelin or promote remyelination. This review aims to summarize studies in the field that highlight the importance of nuclear hormone receptors in the promotion and maintenance of myelination and the relevance of nuclear hormone receptors as potential therapeutic targets for demyelinating diseases. These nuclear hormone receptors include the estrogen receptor, progesterone receptor, androgen receptor, vitamin D receptor, thyroid hormone receptor, peroxisome proliferator-activated receptor, liver X receptor, and retinoid X receptor. Pre-clinical studies in well-established animal models of demyelination have shown a prominent role of these nuclear hormone receptors in myelination through their promotion of oligodendrocyte maturation and development. The activation of the nuclear hormone receptors by their ligands also promotes the synthesis of myelin proteins and lipids in mouse models of demyelination. There are limited clinical studies that focus on how the activation of these nuclear hormone receptors could alleviate demyelination in patients with diseases such as multiple sclerosis (MS). However, the completed clinical trials have reported improved clinical outcome in MS patients treated with the ligands of some of these nuclear hormone receptors. Together, the positive results from both clinical and pre-clinical studies point to nuclear hormone receptors as promising therapeutic targets to counter demyelination.
Topics: Animals; Demyelinating Diseases; Humans; Mice; Multiple Sclerosis; Myelin Sheath; Oligodendroglia; Receptors, Cytoplasmic and Nuclear; Remyelination
PubMed: 35734821
DOI: 10.1111/jne.13171 -
Glia Nov 2019In the central nervous system (CNS), myelin sheaths around axons are formed by glial cells named oligodendrocytes (OLs). In turn, OLs are generated by oligodendrocyte... (Review)
Review
In the central nervous system (CNS), myelin sheaths around axons are formed by glial cells named oligodendrocytes (OLs). In turn, OLs are generated by oligodendrocyte precursor cells (OPCs) during postnatal development and in adults, according to a process that depends on the proliferation and differentiation of these progenitors. The maturation of OL lineage cells as well as myelination by OLs are complex and highly regulated processes in the CNS. OPCs and OLs express an array of receptors for neurotransmitters, in particular for the two main CNS neurotransmitters glutamate and GABA, and are therefore endowed with the capacity to respond to neuronal activity. Initial studies in cell cultures demonstrated that both glutamate and GABA signaling mechanisms play important roles in OL lineage cell development and function. However, much remains to be learned about the communication of glutamatergic and GABAergic neurons with oligodendroglia in vivo. This review focuses on recent major advances in our understanding of the neuron-oligodendroglia communication mediated by glutamate and GABA in the CNS, and highlights the present controversies in the field. We discuss the expression, activation modes and potential roles of synaptic and extrasynaptic receptors along OL lineage progression. We review the properties of OPC synaptic connectivity with presynaptic glutamatergic and GABAergic neurons in the brain and consider the implication of glutamate and GABA signaling in activity-driven adaptive myelination.
Topics: Animals; Axons; Cell Differentiation; Humans; Myelin Sheath; Neurons; Oligodendrocyte Precursor Cells; Oligodendroglia
PubMed: 30957306
DOI: 10.1002/glia.23618