Neuronal activity promotes myelination via a cAMP pathway

Malone, Misti; Gary, Devin S.; Yang, In Hong; Miglioretti, Anna; Houdayer, Thierry; Thakor, Nitish V.; McDonald, John W.

doi:10.1002/glia.22476

Cited by 55 publications

(58 citation statements)

References 83 publications

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“…In addition, elevating cAMP levels enhanced remyelination in a cuprizone demyelination model (Sun et al, 2012). Recently, cAMP was demonstrated to act as an activity-dependent pathway in neurons to promote myelination (Malone et al, 2013). …”

Section: Activity-dependent Remyelination and Oligodendrocyte Respmentioning

confidence: 99%

The axon–glia unit in white matter stroke: Mechanisms of damage and recovery

Rosenzweig

Carmichael

2015

Brain Research

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Approximately one quarter of all strokes in humans occur in white matter, and the progressive nature of white matter lesions often results in severe physical and mental disability. Unlike cortical grey matter stroke, the pathology of white matter stroke revolves around disrupted connectivity and injured axons and glial cells, rather than neuronal cell bodies. Consequently, the mechanisms behind ischemic damage to white matter elements, the regenerative responses of glial cells and their signaling pathways, all differ significantly from those in grey matter. Development of effective therapies for white matter stroke would require an enhanced understanding of the complex cellular and molecular interactions within the white matter, leading to the identification of new therapeutic targets. This review will address the unique properties of the axon-glia unit during white matter stroke, describe the challenging process of promoting effective white matter repair, and discuss recently-identified signaling pathways which may hold potential targets for repair in this disease.

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Section: Activity-dependent Remyelination and Oligodendrocyte Respmentioning

confidence: 99%

The axon–glia unit in white matter stroke: Mechanisms of damage and recovery

Rosenzweig

Carmichael

2015

Brain Research

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“…Contactin deficiency could thus limit the number of sodium channels on axon surfaces, and thereby decrease neuronal activity, which is crucial for myelination and oligodendrocyte differentiation in vitro and in vivo (56)(57)(58)(59). Indeed, Kazarinova-Noyes and Shrager recorded reduced compound action potential velocity in Cntn1-KO optic nerves (60).…”

Section: Contactin In Domain Organization Of Myelinated Central Nervesmentioning

confidence: 99%

Contactin-1 regulates myelination and nodal/paranodal domain organization in the central nervous system

Çolakoğlu

Bergstrom-Tyrberg

Berglund

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Myelin, a multilayered membrane sheath formed by oligodendrocytes around axons in the CNS, enables rapid nerve impulse conduction and sustains neuronal health. The signals exchanged between axons and oligodendrocytes in myelin remain to be fully elucidated. Here we provide genetic evidence for multiple and critical functions of Contactin-1 in central myelin. We document dynamic Contactin-1 expression on oligodendrocytes in vivo, and progressive accumulation at nodes of Ranvier and paranodes during postnatal mouse development. Nodal and paranodal expression stabilized in mature myelin, but overall membranous expression diminished. Contactin-1-deficiency disrupted paranodal junction formation as evidenced by loss of Caspr, mislocalized potassium K v 1.2 channels, and abnormal myelin terminal loops. Reduced numbers and impaired maturation of sodium channel clusters accompanied this phenotype. Histological, electron microscopic, and biochemical analyses uncovered significant hypomyelination in Contactin-1-deficient central nerves, with up to 60% myelin loss. Oligodendrocytes were present in normal numbers, albeit a minor population of neuronal/glial antigen 2-positive (NG2 + ) progenitors lagged in maturation by postnatal day 18, when the mouse null mutation was lethal. Major contributing factors to hypomyelination were defects in the generation and organization of myelin membranes, as judged by electron microscopy and quantitative analysis of oligodendrocyte processes labeled by GFP transgenically expressed from the proteolipid protein promoter. These data reveal that Contactin-1 regulates both myelin formation and organization of nodal and paranodal domains in the CNS. These multiple roles distinguish central Contactin-1 functions from its specific role at paranodes in the periphery, and emphasize mechanistic differences in central and peripheral myelination.

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“…Axons have nonneuronal synaptic connections with glial cells along their length [4,5]. Axonal glutamate release at these synapses drives electrical activity in oligodendrocyte precursor cells that may provide a signal for myelination [6,7 ▪ ,8]. Similarly, dorsal column axons have been shown to express both AMPA and kainate receptors [9] that modulate calcium signaling with axons by triggering calcium release from axonal nanocomplexes [10].…”

Section: New Insights On the Dynamic Function Of Axonsmentioning

confidence: 99%

The back and forth of axonal injury and repair after stroke

Hinman¹

2014

Current Opinion in Neurology

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Purpose of review The axon plays a central role in both the injury and repair phases after stroke. This review highlights emerging principles in the study of axonal injury in stroke and the role of the axon in neural repair after stroke. Recent findings Ischemic stroke produces a rapid and significant loss of axons in the acute phase. This early loss of axons results from a primary ischemic injury that triggers a wave of calcium signaling, activating proteolytic mechanisms and downstream signaling cascades. A second progressive phase of axonal injury occurs during the subacute period and damages axons that survive the initial ischemic insult but go on to experience a delayed axonal degeneration driven in part by changes in axoglial contact and axonal energy metabolism. Recovery from stroke is dependent on axonal sprouting and reconnection that occurs during a third degenerative/regenerative phase. Despite this central role played by the axon, comparatively little is understood about the molecular pathways that contribute to early and subacute axonal degeneration after stroke. Recent advances in axonal neurobiology and signaling suggest new targets that hold promise as potential molecular therapeutics including axonal calcium signaling, axoglial energy metabolism and cell adhesion as well as retrograde axonal mitogen-activated protein kinase pathways. These novel pathways must be modeled appropriately as the type and severity of axonal injury vary by stroke subtype. Summary Stroke-induced injury to axons occurs in three distinct phases each with a unique molecular underpinning. A wealth of new data about the molecular organization and molecular signaling within axons is available but not yet robustly applied to the study of axonal injury after stroke. Identifying the spatiotemporal patterning of molecular pathways within the axon that contribute to injury and repair may offer new therapeutic strategies for the treatment of stroke.

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Neuronal activity promotes myelination via a cAMP pathway

Cited by 55 publications

References 83 publications

The axon–glia unit in white matter stroke: Mechanisms of damage and recovery

The axon–glia unit in white matter stroke: Mechanisms of damage and recovery

Contactin-1 regulates myelination and nodal/paranodal domain organization in the central nervous system

The back and forth of axonal injury and repair after stroke

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