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Current Opinion in Pharmacology Oct 2022Amino acids and their derivatives function as building blocks as well as signaling molecules to modulate various cellular processes in living organisms. In mice, amino... (Review)
Review
Amino acids and their derivatives function as building blocks as well as signaling molecules to modulate various cellular processes in living organisms. In mice, amino acids accumulate in demyelinated lesions and return to basal levels during remyelination. Studies have found that amino acids and their metabolites modulate immune activity in the central nervous system (CNS) and influence oligodendrocyte differentiation and remyelination efficiency. In this review, we discuss current studies on amino acid metabolism in the context of CNS remyelination. By understanding the mechanisms of amino acid signaling and metabolism in demyelinated lesions, we may deepen our understanding of compartmentalized CNS inflammation in demyelinating disease like multiple sclerosis (MS) and provide evidence to develop novel pharmacological therapies targeting amino acid metabolism to prevent disease worsening.
Topics: Amino Acids; Animals; Central Nervous System; Demyelinating Diseases; Mice; Microglia; Multiple Sclerosis; Oligodendroglia; Remyelination
PubMed: 36067684
DOI: 10.1016/j.coph.2022.102287 -
Neuroscience Bulletin Mar 2023Glial cells in the central nervous system (CNS) are composed of oligodendrocytes, astrocytes and microglia. They contribute more than half of the total cells of the CNS,... (Review)
Review
Glial cells in the central nervous system (CNS) are composed of oligodendrocytes, astrocytes and microglia. They contribute more than half of the total cells of the CNS, and are essential for neural development and functioning. Studies on the fate specification, differentiation, and functional diversification of glial cells mainly rely on the proper use of cell- or stage-specific molecular markers. However, as cellular markers often exhibit different specificity and sensitivity, careful consideration must be given prior to their application to avoid possible confusion. Here, we provide an updated overview of a list of well-established immunological markers for the labeling of central glia, and discuss the cell-type specificity and stage dependency of their expression.
Topics: Neuroglia; Central Nervous System; Oligodendroglia; Astrocytes; Microglia
PubMed: 36028641
DOI: 10.1007/s12264-022-00938-2 -
Molecular Neurobiology Apr 2013α-Synuclein (AS)-positive inclusions are the pathological hallmark of Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), all... (Review)
Review
α-Synuclein (AS)-positive inclusions are the pathological hallmark of Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), all belonging to the category of α-synucleinopathies. α-Synucleinopathies represent progressive neurodegenerative disorders characterised by increasing incidences in the population over the age of 65. The relevance of glial reactivity and dysfunction in α-synucleinopathies is highlighted by numerous experimental evidences. Glial AS inclusion pathology is prominent in oligodendroglia of MSA (glial cytoplasmic inclusions) and is a common finding in astroglial cells of PD and DLB, resulting in specific dysfunctional responses. Involvement of AS-dependent astroglial and microglial activation in neurodegenerative mechanisms, and therefore in disease initiation and progression, has been suggested. The aim of this review is to summarise and discuss the multifaceted responses of glial cells in α-synucleinopathies. The beneficial, as well as detrimental, effects of glial cells on neuronal viability are taken into consideration to draw an integrated picture of glial roles in α-synucleinopathies. Furthermore, an overview on therapeutic approaches outlines the difficulties of translating promising experimental studies into successful clinical trials targeting candidate glial pathomechanisms.
Topics: Animals; Humans; Neurodegenerative Diseases; Neuroglia; Neurons; Oligodendroglia; alpha-Synuclein
PubMed: 22941028
DOI: 10.1007/s12035-012-8340-3 -
Seminars in Cell & Developmental Biology Oct 2021During cortical development and throughout adulthood, oligodendrocytes add myelin internodes to glutamatergic projection neurons and GABAergic inhibitory neurons. In... (Review)
Review
During cortical development and throughout adulthood, oligodendrocytes add myelin internodes to glutamatergic projection neurons and GABAergic inhibitory neurons. In addition to directing node of Ranvier formation, to enable saltatory conduction and influence action potential transit time, oligodendrocytes support axon health by communicating with axons via the periaxonal space and providing metabolic support that is particularly critical for healthy ageing. In this review we outline the timing of oligodendrogenesis in the developing mouse and human cortex and describe the important role that oligodendrocytes play in sustaining and modulating neuronal function. We also provide insight into the known and speculative impact that myelination has on cortical axons and their associated circuits during the developmental critical periods and throughout life, particularly highlighting their life-long role in learning and remembering.
Topics: Animals; Cerebellar Cortex; Humans; Mice; Myelin Sheath; Neuronal Plasticity; Oligodendroglia
PubMed: 33863642
DOI: 10.1016/j.semcdb.2021.03.017 -
Cells Oct 2019Microglia originate from yolk sac-primitive macrophages and auto-proliferate into adulthood without replacement by bone marrow-derived circulating cells. In... (Review)
Review
Microglia originate from yolk sac-primitive macrophages and auto-proliferate into adulthood without replacement by bone marrow-derived circulating cells. In inflammation, stroke, aging, or infection, microglia have been shown to contribute to brain pathology in both deleterious and beneficial ways, which have been studied extensively. However, less is known about their role in the healthy adult brain. Astrocytes and oligodendrocytes are widely accepted to strongly contribute to the maintenance of brain homeostasis and to modulate neuronal function. On the other hand, contribution of microglia to cognition and behavior is only beginning to be understood. The ability to probe their function has become possible using microglial depletion assays and conditional mutants. Studies have shown that the absence of microglia results in cognitive and learning deficits in rodents during development, but this effect is less pronounced in adults. However, evidence suggests that microglia play a role in cognition and learning in adulthood and, at a cellular level, may modulate adult neurogenesis. This review presents the case for repositioning microglia as key contributors to the maintenance of homeostasis and cognitive processes in the healthy adult brain, in addition to their classical role as sentinels coordinating the neuroinflammatory response to tissue damage and disease.
Topics: Adult; Animals; Astrocytes; Brain; Cognition; Humans; Learning; Microglia; Oligodendroglia
PubMed: 31652490
DOI: 10.3390/cells8101293 -
Acta Neuropathologica Jan 2010Oligodendrocytes are the myelinating cells of the central nervous system (CNS). They are the end product of a cell lineage which has to undergo a complex and precisely... (Review)
Review
Oligodendrocytes are the myelinating cells of the central nervous system (CNS). They are the end product of a cell lineage which has to undergo a complex and precisely timed program of proliferation, migration, differentiation, and myelination to finally produce the insulating sheath of axons. Due to this complex differentiation program, and due to their unique metabolism/physiology, oligodendrocytes count among the most vulnerable cells of the CNS. In this review, we first describe the different steps eventually culminating in the formation of mature oligodendrocytes and myelin sheaths, as they were revealed by studies in rodents. We will then show differences and similarities of human oligodendrocyte development. Finally, we will lay out the different pathways leading to oligodendrocyte and myelin loss in human CNS diseases, and we will reveal the different principles leading to the restoration of myelin sheaths or to a failure to do so.
Topics: Animals; Cell Death; Central Nervous System; Central Nervous System Diseases; Humans; Myelin Sheath; Nerve Fibers, Myelinated; Oligodendroglia; Species Specificity
PubMed: 19847447
DOI: 10.1007/s00401-009-0601-5 -
Neuron Oct 2021Oligodendrocyte (OL) maturation arrest in human white matter injury contributes significantly to the failure of endogenous remyelination in multiple sclerosis (MS) and...
Oligodendrocyte (OL) maturation arrest in human white matter injury contributes significantly to the failure of endogenous remyelination in multiple sclerosis (MS) and newborn brain injuries such as hypoxic ischemic encephalopathy (HIE) that cause cerebral palsy. In this study, we identify an oligodendroglial-intrinsic factor that controls OL maturation specifically in the setting of injury. We find a requirement for the ring finger protein Rnf43 not in normal development but in neonatal hypoxic injury and remyelination in the adult mammalian CNS. Rnf43, but not the related Znrf3, is potently activated by Wnt signaling in OL progenitor cells (OPCs) and marks activated OPCs in human MS and HIE. Rnf43 is required in an injury-specific context, and it promotes OPC differentiation through negative regulation of Wnt signal strength in OPCs at the level of Fzd1 receptor presentation on the cell surface. Inhibition of Fzd1 using UM206 promotes remyelination following ex vivo and in vivo demyelinating injury.
Topics: Animals; Brain Injuries; Demyelinating Diseases; Frizzled Receptors; Humans; Mice; Myelin Sheath; Oligodendroglia; Remyelination; Stem Cells; Ubiquitin-Protein Ligases; White Matter; Wnt Signaling Pathway
PubMed: 34390652
DOI: 10.1016/j.neuron.2021.07.018 -
Current Opinion in Pharmacology Apr 2022Chronically demyelinated axons are rendered susceptible to degeneration through loss of trophic support from oligodendrocytes and myelin, and this process underlies... (Review)
Review
Chronically demyelinated axons are rendered susceptible to degeneration through loss of trophic support from oligodendrocytes and myelin, and this process underlies disability progression in multiple sclerosis. Promoting remyelination is a promising neuroprotective therapeutic strategy, but to date, has not been achieved through simply promoting oligodendrocyte precursor cell differentiation, and it is clear that a detailed understanding of the molecular mechanisms underlying failed remyelination is required to guide future therapeutic approaches. In multiple sclerosis, remyelination is impaired by extrinsic inhibitory cues in the lesion microenvironment including secreted effector molecules released from compartmentalized immune cells and reactive glia, as well as by intrinsic defects in oligodendrocyte lineage cells, most notably increased metabolic demands causing oxidative stress and accelerated cellular senescence. Promising advances in our understanding of the cellular and molecular mechanisms underlying these processes offers hope for strategically designed interventions to facilitate remyelination thereby resulting in robust clinical benefits.
Topics: Cell Differentiation; Humans; Multiple Sclerosis; Myelin Sheath; Oligodendroglia; Remyelination
PubMed: 35255453
DOI: 10.1016/j.coph.2022.102194 -
Communications Biology Nov 2022Myelin, the membrane surrounding neuronal axons, is critical for central nervous system (CNS) function. Injury to myelin-forming oligodendrocytes (OL) in chronic... (Review)
Review
Myelin, the membrane surrounding neuronal axons, is critical for central nervous system (CNS) function. Injury to myelin-forming oligodendrocytes (OL) in chronic neurological diseases (e.g. multiple sclerosis) ranges from sublethal to lethal, leading to OL dysfunction and myelin pathology, and consequent deleterious impacts on axonal health that drive clinical impairments. This is regulated by intrinsic factors such as heterogeneity and age, and extrinsic cellular and molecular interactions. Here, we discuss the responses of OLs to injury, and perspectives for therapeutic targeting. We put forward that targeting mature OL health in neurological disease is a promising therapeutic strategy to support CNS function.
Topics: Humans; Oligodendroglia; Myelin Sheath; Central Nervous System; Axons; Multiple Sclerosis
PubMed: 36402839
DOI: 10.1038/s42003-022-04248-1 -
Journal of Neurochemistry Apr 2018Myelin, an insulating membrane that enables rapid action potential propagation, is an essential component of an efficient, functional vertebrate nervous system.... (Review)
Review
Myelin, an insulating membrane that enables rapid action potential propagation, is an essential component of an efficient, functional vertebrate nervous system. Oligodendrocytes, the myelinating glia of the central nervous system (CNS), produce myelin throughout the CNS, which requires continuous proliferation, migration, and differentiation of oligodendrocyte progenitor cells. Because myelination is essential for efficient neurotransmission, researchers hypothesize that neuronal signals may regulate the cascade of events necessary for this process. The ability of oligodendrocytes and oligodendrocyte progenitor cells to detect and respond to neuronal activity is becoming increasingly appreciated, although the specific signals involved are still a matter of debate. Recent evidence from multiple studies points to purinergic signaling as a potential regulator of oligodendrocyte development and differentiation. Adenosine triphosphate (ATP) and its derivatives are potent signaling ligands with receptors expressed on many populations of cells in the nervous system, including cells of the oligodendrocyte lineage. Release of ATP into the extracellular space can initiate a multitude of signaling events, and these downstream signals are specific to the particular purinergic receptor (or receptors) expressed, and whether enzymes are present to hydrolyze ATP to its derivatives adenosine diphosphate and adenosine, each of which can activate their own unique downstream signaling cascades. This review will introduce purinergic signaling in the CNS and discuss evidence for its effects on oligodendrocyte proliferation, differentiation, and myelination. We will review sources of extracellular purines in the nervous system and how changes in purinergic receptor expression may be coupled to oligodendrocyte differentiation. We will also briefly discuss purinergic signaling in injury and diseases of the CNS.
Topics: Animals; Cell Differentiation; Central Nervous System; Humans; Neural Stem Cells; Neurogenesis; Oligodendroglia; Receptors, Purinergic; Signal Transduction
PubMed: 29377124
DOI: 10.1111/jnc.14315