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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 -
Developmental Cell Jul 2021Developmental myelination is a protracted process that extends well into postnatal life. Cell-intrinsic mechanisms operate in myelin-forming oligodendrocytes, as well as... (Review)
Review
Developmental myelination is a protracted process that extends well into postnatal life. Cell-intrinsic mechanisms operate in myelin-forming oligodendrocytes, as well as microenvironmental interactions that guide and modulate every aspect of myelination, from oligodendrocyte precursor cell migration to oligodendrocyte differentiation and the formation of stable myelin internodes. During development and throughout adult life, neuron-oligodendroglial interactions shape activity and experience-dependent myelin adaptations to fine-tune neural circuit dynamics and promote healthy neurological function.
Topics: Cell Differentiation; Cell Movement; Cellular Microenvironment; Humans; Myelin Sheath; Neurons; Oligodendroglia
PubMed: 34192527
DOI: 10.1016/j.devcel.2021.06.006 -
Current Opinion in Neurobiology Dec 2017Myelin increases the speed and efficiency of action potential propagation. Yet, not all axons are myelinated and some axons are discontinuously myelinated, prompting the... (Review)
Review
Myelin increases the speed and efficiency of action potential propagation. Yet, not all axons are myelinated and some axons are discontinuously myelinated, prompting the question of how myelinating glia select axons for myelination. Whereas myelination by Schwann cells depends on axonal induction, oligodendrocytes can form myelin membrane in the absence of axons. However, oligodendrocytes alone cannot architect the complex myelination patterns of the central nervous system and recent advances have implicated axonal signaling in this process. This review considers how oligodendrocytes and their precursors could be influenced by inductive, attractive, permissive, repulsive, and preventative cues, and discusses recent evidence identifying synaptic activity and membrane-bound adhesion molecules as such cues directing axon selection.
Topics: Animals; Axons; Central Nervous System; Humans; Myelin Sheath; Neural Stem Cells; Oligodendroglia
PubMed: 28709021
DOI: 10.1016/j.conb.2017.06.005 -
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 -
Molecular Metabolism Mar 2023Oligodendrocyte progenitor cell differentiation is regulated by nutritional signals in the adult median eminence (ME), but the consequences on local myelination are...
OBJECTIVE
Oligodendrocyte progenitor cell differentiation is regulated by nutritional signals in the adult median eminence (ME), but the consequences on local myelination are unknown. The aim of this study was to characterize myelin plasticity in the ME of adult mice in health or in response to chronic nutritional challenge and determine its relevance to the regulation of energy balance.
METHODS
We assessed new oligodendrocyte (OL) and myelin generation and stability in the ME of healthy adult male mice using bromodeoxyuridine labelling and genetic fate mapping tools. We evaluated the contribution of microglia to ME myelin plasticity in PLX5622-treated C57BL/6J mice and in Pdgfra-Cre/ER;R26R-eYFP;Myrf mice, where adult oligodendrogenesis is blunted. Next, we investigated how high-fat feeding or caloric restriction impact ME OL lineage progression and myelination. Finally, we characterized the functional relevance of adult oligodendrogenesis on energy balance regulation.
RESULTS
We show that myelinating OLs are continuously and rapidly generated in the adult ME. Paradoxically, OL number and myelin amounts remain remarkably stable in the adult ME. In fact, the high rate of new OL and myelin generation in the ME is offset by continuous turnover of both. We show that microglia are required for continuous OL and myelin production, and that ME myelin plasticity regulates the recruitment of local immune cells. Finally, we provide evidence that ME myelination is regulated by the body's energetic status and demonstrate that ME OL and myelin plasticity are required for the regulation of energy balance and hypothalamic leptin sensitivity.
CONCLUSIONS
This study identifies a new mechanism modulating leptin sensitivity and the central control of energy balance and uncovers a previously unappreciated form of structural plasticity in the ME.
Topics: Mice; Male; Animals; Myelin Sheath; Leptin; Mice, Transgenic; Median Eminence; Mice, Inbred C57BL
PubMed: 36739968
DOI: 10.1016/j.molmet.2023.101690 -
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 -
Acta Neuropathologica Communications Mar 2023Alzheimer's disease (AD) is a neurodegenerative disorder with neuronal and synaptic losses due to the accumulation of toxic amyloid β (Αβ) peptide oligomers, plaques,... (Review)
Review
Alzheimer's disease (AD) is a neurodegenerative disorder with neuronal and synaptic losses due to the accumulation of toxic amyloid β (Αβ) peptide oligomers, plaques, and tangles containing tau (tubulin-associated unit) protein. While familial AD is caused by specific mutations, the sporadic disease is more common and appears to result from a complex chronic brain neuroinflammation with mitochondriopathies, inducing free radicals' accumulation. In aged brain, mutations in DNA and several unfolded proteins participate in a chronic amyloidosis response with a toxic effect on myelin sheath and axons, leading to cognitive deficits and dementia. Αβ peptides are the most frequent form of toxic amyloid oligomers. Accumulations of misfolded proteins during several years alters different metabolic mechanisms, induce chronic inflammatory and immune responses with toxic consequences on neuronal cells. Myelin composition and architecture may appear to be an early target for the toxic activity of Aβ peptides and others hydrophobic misfolded proteins. In this work, we describe the possible role of early myelin alterations in the genesis of neuronal alterations and the onset of symptomatology. We propose that some pathophysiological and clinical forms of the disease may arise from structural and metabolic disorders in the processes of myelination/demyelination of brain regions where the accumulation of non-functional toxic proteins is important. In these forms, the primacy of the deleterious role of amyloid peptides would be a matter of questioning and the initiating role of neuropathology would be primarily the fact of dysmyelination.
Topics: Humans; Aged; Alzheimer Disease; Amyloid beta-Peptides; Myelin Sheath; Axons; Neurons
PubMed: 37004127
DOI: 10.1186/s40478-023-01554-5 -
Yakugaku Zasshi : Journal of the... 2022Myelin is a multilamellar membrane structure formed by oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS). It... (Review)
Review
Myelin is a multilamellar membrane structure formed by oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS). It has been recognized as an insulator that is essential for the rapid and efficient propagation of action potentials by saltatory conduction. However, recently many studies have shown that myelin and myelin-forming cells interact with axons and regulate the nervous system far more actively than previously thought. For example, myelination changes axons dynamically and divides them into four distinct functional domains: node of Ranvier, paranode, juxtaparanode, and internode. Voltage-gated Na channels are clustered at the node, while K channels are at the juxtaparanode, and segregation of these channels by paranodal axoglial junction is necessary for proper axonal function. My research experience began at the neurology ward of the Niigata University Medical Hospital, where I saw a patient with peripheral neuropathy of unknown etiology more than 37 years ago. In the patient's serum, we found an autoantibody against a glycolipid enriched in the PNS. Since then, I have been interested in myelin because of its beautiful structure and unique roles in the nervous system. In this review, our recent studies related to CNS and PNS myelin are presented.
Topics: Autoantibodies; Axons; Central Nervous System; Humans; Myelin Sheath; Ranvier's Nodes; Schwann Cells
PubMed: 35908945
DOI: 10.1248/yakushi.21-00224 -
Progress in Neurobiology Jul 2023Oligodendrocytes are responsible for myelinating central nervous system (CNS) axons and rapid electrical transmission through saltatory conduction of action potentials.... (Review)
Review
Oligodendrocytes are responsible for myelinating central nervous system (CNS) axons and rapid electrical transmission through saltatory conduction of action potentials. Myelination and myelin repair rely partially on oligodendrogenesis, which comprises oligodendrocyte precursor cell (OPC) migration, maturation, and differentiation into oligodendrocytes (OL). In multiple sclerosis (MS), demyelination occurs due to an inflammatory cascade with auto-reactive T-cells. When oligodendrogenesis fails, remyelination becomes aberrant and conduction impairments are no longer restored. Although current disease modifying therapies have achieved results in modulating the faulty immune response, disease progression continues because of chronic inflammation, neurodegeneration, and failure of remyelination. Therapies have been tried to promote remyelination. Modulation of neuronal activity seems to be a very promising strategy in preclinical studies. Additionally, studies in people with MS (pwMS) have shown symptom improvement following non-invasive brain stimulation. (NIBS) techniques. The aforementioned mechanisms are yet unknown and probably involve both the activation of neurons and glial cells. Noting neuronal activity contributes to myelin plasticity and that NIBS modulates neuronal activity; we argue that NIBS is a promising research horizon for demyelinating diseases. We review the hypothesized pathways through which NIBS may affect both neuronal activity in the CNS and how the resulting activity can affect oligodendrogenesis and myelination.
Topics: Humans; Remyelination; Myelin Sheath; Oligodendroglia; Multiple Sclerosis; Cell Differentiation
PubMed: 37127087
DOI: 10.1016/j.pneurobio.2023.102459 -
The Journal of Endocrinology Aug 2023Myelination allows fast and synchronized nerve influxes and is provided by Schwann cells (SCs) in the peripheral nervous system. Glucocorticoid hormones are major...
Myelination allows fast and synchronized nerve influxes and is provided by Schwann cells (SCs) in the peripheral nervous system. Glucocorticoid hormones are major regulators of stress, metabolism and immunity affecting all tissues. They act by binding to two receptors, the low-affinity glucocorticoid receptor (GR) and the high-affinity mineralocorticoid receptor (MR). Little is known about the effect of glucocorticoid hormones on the PNS, and this study focuses on deciphering the role of MR in peripheral myelination. In this work, the presence of a functional MR in SCs is demonstrated and the expression of MR protein in mouse sciatic nerve SC is evidenced. Besides, knockout of MR in SC (SCMRKO using Cre-lox system with DesertHedgeHog (Dhh) Cre promoter) was undertaken in mice. SCMRKO was not associated with alterations of performance in motor behavioral tests on 2- to 6-month-old male mice compared to their controls. No obvious modifications of myelin gene expression or MR signaling gene expression were observed in the SCMRKO sciatic nerves. Nevertheless, Gr transcript and GR protein amounts were significantly increased in SCMRKO nerves compared to controls, suggesting a possible compensatory effect. Besides, an increase in myelin sheath thickness was noted for axons with perimeters larger than 15 µm in SCMRKO illustrated by a significant 4.5% reduction in g-ratio (axon perimeter/myelin sheath perimeter). Thus, we defined MR as a new player in peripheral system myelination and in SC homeostasis.
Topics: Male; Mice; Animals; Myelin Sheath; Receptors, Mineralocorticoid; Glucocorticoids; Mice, Knockout; Schwann Cells; Sciatic Nerve
PubMed: 37195271
DOI: 10.1530/JOE-22-0334