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Current Biology : CB Oct 2016Myelin is a key evolutionary acquisition that underlay the development of the large, complex nervous systems of all hinged-jaw vertebrates. By promoting rapid, efficient...
Myelin is a key evolutionary acquisition that underlay the development of the large, complex nervous systems of all hinged-jaw vertebrates. By promoting rapid, efficient nerve conduction, myelination also made possible the development of the large body size of these vertebrates. In addition to increasing the speed of nerve conduction, myelination has emerged as a source of plasticity in neural circuits that is crucial for proper timing and function. Here, we briefly describe the organization of myelin and of myelinated axons, as well as the functions of myelin in nerve conduction and neural circuits, and consider its potential evolutionary origins.
Topics: Animals; Axons; Biological Evolution; Myelin Sheath; Nerve Fibers, Myelinated; Neural Conduction; Vertebrates
PubMed: 27780071
DOI: 10.1016/j.cub.2016.07.074 -
Neuron Aug 2018To address the significance of enhancing myelination for functional recovery after white matter injury (WMI) in preterm infants, we characterized hypomyelination...
To address the significance of enhancing myelination for functional recovery after white matter injury (WMI) in preterm infants, we characterized hypomyelination associated with chronic hypoxia and identified structural and functional deficits of excitatory cortical synapses with a prolonged motor deficit. We demonstrate that genetically delaying myelination phenocopies the synaptic and functional deficits observed in mice after hypoxia, suggesting that myelination may possibly facilitate excitatory presynaptic innervation. As a gain-of-function experiment, we specifically ablated the muscarinic receptor 1 (M1R), a negative regulator of oligodendrocyte differentiation in oligodendrocyte precursor cells. Genetically enhancing oligodendrocyte differentiation and myelination rescued the synaptic loss after chronic hypoxia and promoted functional recovery. As a proof of concept, drug-based myelination therapies also resulted in accelerated differentiation and myelination with functional recovery after chronic hypoxia. Together, our data indicate that myelination-enhancing strategies in preterm infants may represent a promising therapeutic approach for structural/functional recovery after hypoxic WMI.
Topics: Animals; Animals, Newborn; Chronic Disease; Female; Hypoxia; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Myelin Sheath; Neurogenesis; Oligodendroglia; Receptor, Muscarinic M1; Recovery of Function; Synapses
PubMed: 30078577
DOI: 10.1016/j.neuron.2018.07.017 -
The Journal of Neuroscience : the... Jan 2020Autophagy is the cellular process involved in transportation and degradation of membrane, proteins, pathogens, and organelles. This fundamental cellular process is vital... (Review)
Review
Autophagy is the cellular process involved in transportation and degradation of membrane, proteins, pathogens, and organelles. This fundamental cellular process is vital in development, plasticity, and response to disease and injury. Compared with neurons, little information is available on autophagy in glia, but it is paramount for glia to perform their critical responses to nervous system disease and injury, including active tissue remodeling and phagocytosis. In myelinating glia, autophagy has expanded roles, particularly in phagocytosis of mature myelin and in generating the vast amounts of membrane proteins and lipids that must be transported to form new myelin. Notably, autophagy plays important roles in removing excess cytoplasm to promote myelin compaction and development of oligodendrocytes, as well as in remyelination by Schwann cells after nerve trauma. This review summarizes the cell biology of autophagy, detailing the major pathways and proteins involved, as well as the roles of autophagy in Schwann cells and oligodendrocytes in development, plasticity, and diseases in which myelin is affected. This includes traumatic brain injury, Alexander's disease, Alzheimer's disease, hypoxia, multiple sclerosis, hereditary spastic paraplegia, and others. Promising areas for future research are highlighted.
Topics: Animals; Autophagy; Humans; Myelin Sheath; Neuroglia
PubMed: 31744863
DOI: 10.1523/JNEUROSCI.1066-19.2019 -
Neuron Dec 2020Myelination facilitates rapid axonal conduction, enabling efficient communication across different parts of the nervous system. Here we examined mechanisms controlling...
Myelination facilitates rapid axonal conduction, enabling efficient communication across different parts of the nervous system. Here we examined mechanisms controlling myelination after injury and during axon regeneration in the central nervous system (CNS). Previously, we discovered multiple molecular pathways and strategies that could promote robust axon regrowth after optic nerve injury. However, regenerated axons remain unmyelinated, and the underlying mechanisms are elusive. In this study, we found that, in injured optic nerves, oligodendrocyte precursor cells (OPCs) undergo transient proliferation but fail to differentiate into mature myelination-competent oligodendrocytes, reminiscent of what is observed in human progressive multiple sclerosis. Mechanistically, we showed that OPC-intrinsic GPR17 signaling and sustained activation of microglia inhibit different stages of OPC differentiation. Importantly, co-manipulation of GPR17 and microglia led to extensive myelination of regenerated axons. The regulatory mechanisms of stage-dependent OPC differentiation uncovered here suggest a translatable strategy for efficient de novo myelination after CNS injury.
Topics: Animals; Axons; Cell Differentiation; Cell Proliferation; Female; Male; Mice; Mice, Transgenic; Microglia; Myelin Sheath; Nerve Fibers, Myelinated; Nerve Regeneration; Nerve Tissue Proteins; Oligodendrocyte Precursor Cells; Random Allocation; Receptors, G-Protein-Coupled
PubMed: 33108748
DOI: 10.1016/j.neuron.2020.09.016 -
Glia Apr 2018Myelinating cells surround axons to accelerate the propagation of action potentials, to support axonal health, and to refine neural circuits. Myelination is... (Review)
Review
Myelinating cells surround axons to accelerate the propagation of action potentials, to support axonal health, and to refine neural circuits. Myelination is metabolically demanding and, consistent with this notion, mTORC1-a signaling hub coordinating cell metabolism-has been implicated as a key signal for myelination. Here, we will discuss metabolic aspects of myelination, illustrate the main metabolic processes regulated by mTORC1, and review advances on the role of mTORC1 in myelination of the central nervous system and the peripheral nervous system. Recent progress has revealed a complex role of mTORC1 in myelinating cells that includes, besides positive regulation of myelin growth, additional critical functions in the stages preceding active myelination. Based on the available evidence, we will also highlight potential nonoverlapping roles between mTORC1 and its known main upstream pathways PI3K-Akt, Mek-Erk1/2, and AMPK in myelinating cells. Finally, we will discuss signals that are already known or hypothesized to be responsible for the regulation of mTORC1 activity in myelinating cells.
Topics: Animals; Humans; Myelin Sheath; TOR Serine-Threonine Kinases
PubMed: 29210103
DOI: 10.1002/glia.23273 -
Cell Sep 2019Microtubules are critical for the extension of oligodendrocyte processes and myelin deposition, yet our knowledge of their microtubule biogenesis is limited. In this...
Microtubules are critical for the extension of oligodendrocyte processes and myelin deposition, yet our knowledge of their microtubule biogenesis is limited. In this issue of Cell, Fu et al. (2019) identify an oligodendrocyte-enriched microtubule regulator that promotes microtubule growth from Golgi outposts and controls myelin sheath elongation, linking microtubule cytoarchitecture and myelination in the CNS.
Topics: Microtubules; Myelin Sheath; Oligodendroglia
PubMed: 31522889
DOI: 10.1016/j.cell.2019.08.046 -
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 -
Nature Neuroscience Oct 2022Myelin plasticity occurs when newly formed and pre-existing oligodendrocytes remodel existing patterns of myelination. Myelin remodeling occurs in response to changes in...
Myelin plasticity occurs when newly formed and pre-existing oligodendrocytes remodel existing patterns of myelination. Myelin remodeling occurs in response to changes in neuronal activity and is required for learning and memory. However, the link between behavior-induced neuronal activity and circuit-specific changes in myelination remains unclear. Using longitudinal in vivo two-photon imaging and targeted labeling of learning-activated neurons in mice, we explore how the pattern of intermittent myelination is altered on individual cortical axons during learning of a dexterous reach task. We show that behavior-induced myelin plasticity is targeted to learning-activated axons and occurs in a staged response across cortical layers in the mouse primary motor cortex. During learning, myelin sheaths retract, which results in lengthening of nodes of Ranvier. Following motor learning, addition of newly formed myelin sheaths increases the number of continuous stretches of myelination. Computational modeling suggests that motor learning-induced myelin plasticity initially slows and subsequently increases axonal conduction speed. Finally, we show that both the magnitude and timing of nodal and myelin dynamics correlate with improvement of behavioral performance during motor learning. Thus, learning-induced and circuit-specific myelination changes may contribute to information encoding in neural circuits during motor learning.
Topics: Animals; Axons; Learning; Mice; Myelin Sheath; Neurons; Oligodendroglia
PubMed: 36180791
DOI: 10.1038/s41593-022-01169-4 -
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 -
Frontiers in Neural Circuits 2019Histological studies of myelin-stained sectioned cadaver brain and myelin-weighted magnetic resonance imaging (MRI) show that the cerebral cortex is organized into... (Review)
Review
Histological studies of myelin-stained sectioned cadaver brain and myelin-weighted magnetic resonance imaging (MRI) show that the cerebral cortex is organized into cortical areas with generally well-defined boundaries, which have consistent internal patterns of myelination. The process of myelination is largely driven by neural experience, in which the axonal passage of action potentials stimulates neighboring oligodendrocytes to perform their task. This bootstrapping process, such that the traffic of action potentials facilitates increased traffic, suggests the hypothesis that the specific pattern of myelination (myeloarchitecture) in each cortical area reveals the principal cortical microcircuits required for the function of that area. If this idea is correct, the observable sequential maturation of specific brain areas can provide evidence for models of the stages of cognitive development.
Topics: Animals; Cerebral Cortex; Humans; Models, Neurological; Myelin Sheath; Nerve Fibers, Myelinated; Neural Pathways
PubMed: 31133821
DOI: 10.3389/fncir.2019.00034