Myelination of the Nervous System: Mechanisms and Functions

Nave, Klaus‐Armin; Werner, Hauke

doi:10.1146/annurev-cellbio-100913-013101

Cited by 757 publications

(700 citation statements)

References 306 publications

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“…It is an open question whether the process of axonal dystrophy is directly caused by the astrocytes through, for example, lack of energy supply or secretion of a toxic factor, or mediated through the impact of astrocytes on oligodendrocytes and their ability to provide metabolic support to axons 34, 35. The effect of astrocytes on axonal density may be related to immaturity of VWM astrocytes, which better promote axonal growth or regeneration than mature astrocytes, while having no differential effect on dendrite growth 36, 37, 38, 39.…”

Section: Discussionmentioning

confidence: 99%

Axonal abnormalities in vanishing white matter

Klok

Bugiani

Vries

et al. 2018

Ann Clin Transl Neurol

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ObjectiveWe aimed to study the occurrence and development of axonal pathology and the influence of astrocytes in vanishing white matter.MethodsAxons and myelin were analyzed using electron microscopy and immunohistochemistry on Eif2b4 and Eif2b5 single‐ and double‐mutant mice and patient brain tissue. In addition, astrocyte‐forebrain co‐culture studies were performed.ResultsIn the corpus callosum of Eif2b5‐mutant mice, myelin sheath thickness, axonal diameter, and G‐ratio developed normally up to 4 months. At 7 months, however, axons had become thinner, while in control mice axonal diameters had increased further. Myelin sheath thickness remained close to normal, resulting in an abnormally low G‐ratio in Eif2b5‐mutant mice. In more severely affected Eif2b4‐Eif2b5 double‐mutants, similar abnormalities were already present at 4 months, while in milder affected Eif2b4 mutants, few abnormalities were observed at 7 months. Additionally, from 2 months onward an increased percentage of thin, unmyelinated axons and increased axonal density were present in Eif2b5‐mutant mice. Co‐cultures showed that Eif2b5 mutant astrocytes induced increased axonal density, also in control forebrain tissue, and that control astrocytes induced normal axonal density, also in mutant forebrain tissue. In vanishing white matter patient brains, axons and myelin sheaths were thinner than normal in moderately and severely affected white matter. In mutant mice and patients, signs of axonal transport defects and cytoskeletal abnormalities were minimal.InterpretationIn vanishing white matter, axons are initially normal and atrophy later. Astrocytes are central in this process. If therapy becomes available, axonal pathology may be prevented with early intervention.

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Section: Discussionmentioning

confidence: 99%

Axonal abnormalities in vanishing white matter

Klok

Bugiani

Vries

et al. 2018

Ann Clin Transl Neurol

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“…Initially, differentiating oligodendrocyte precursor cells will extend their processes and will either retract them or form stable contacts with axonal targets (Nave and Werner, 2014). These axon-glial contacts will further progress into complex three-dimensional radial and lateral ensheathing or wrapping structures, and will finally rest after a certain thickness of the growing myelin sheath has been established (Snaidero et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Oligodendroglial maturation and myelination are complex cell biological processes requiring tightly regulated control mechanisms. Several signaling pathways have been described that are required for forming myelin membranes in vitro and in vivo (Nave and Werner, 2014;White and Krämer-Albers, 2014). Among those, the activation of the oligodendroglial non-receptor tyrosine kinase Fyn has been proposed to be of central importance (Krämer-Albers and White, 2011).…”

Section: Introductionmentioning

confidence: 99%

MOBP levels are regulated by Fyn kinase and affect the morphological differentiation of oligodendrocytes

Schäfer

Müller

Luhmann

et al. 2016

Journal of Cell Science

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Oligodendrocytes are the myelinating glial cells of the central nervous system (CNS). Myelin is formed by extensive wrapping of oligodendroglial processes around axonal segments, which ultimately allows a rapid saltatory conduction of action potentials within the CNS and sustains neuronal health. The non-receptor tyrosine kinase Fyn is an important signaling molecule in oligodendrocytes. It controls the morphological differentiation of oligodendrocytes and is an integrator of axon-glial signaling cascades leading to localized synthesis of myelin basic protein (MBP), which is essential for myelin formation. The abundant myelinassociated oligodendrocytic basic protein (MOBP) resembles MBP in several aspects and has also been reported to be localized as mRNA and translated in the peripheral myelin compartment. The signals initiating local MOBP synthesis are so far unknown and the cellular function of MOBP remains elusive. Here, we show, by several approaches in cultured primary oligodendrocytes, that MOBP synthesis is stimulated by Fyn activity. Moreover, we reveal a new function for MOBP in oligodendroglial morphological differentiation.

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“…The rapid transmission of sensory and motor information in the peripheral nervous system is permitted by the myelin sheath, which is formed by myelinating Schwann cells (SCs) 1 . Insulation of axons by the myelin sheath enables saltatory conduction, which increases the speed of nerve impulses.…”

Section: Introductionmentioning

confidence: 99%

<em>In Vivo</em> Gene Transfer to Schwann Cells in the Rodent Sciatic Nerve by Electroporation

Ino

Iino

2016

JoVE

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The formation of the myelin sheath by Schwann cells (SCs) is essential for rapid conduction of nerve impulses along axons in the peripheral nervous system. SC-selective genetic manipulation in living animals is a powerful technique for studying the molecular and cellular mechanisms of SC myelination and demyelination in vivo. While knockout/knockin and transgenic mice are powerful tools for studying SC biology, these methods are costly and time consuming. Viral vector-mediated transgene introduction into the sciatic nerve is a simpler and less laborious method. However, viral methods have limitations, such as toxicity, transgene size constraints, and infectivity restricted to certain developmental stages. Here, we describe a new method that allows selective transfection of myelinating SCs in the rodent sciatic nerve using electroporation. By applying electric pulses to the sciatic nerve at the site of plasmid DNA injection, genes of interest can be easily silenced or overexpressed in SCs in both neonatal and more mature animals. Furthermore, this in vivo electroporation method allows for highly efficient simultaneous expression of multiple transgenes. Our novel technique should enable researchers to efficiently manipulate SC gene expression, and facilitate studies on SC development and function.

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Myelination of the Nervous System: Mechanisms and Functions

Cited by 757 publications

References 306 publications

Axonal abnormalities in vanishing white matter

Axonal abnormalities in vanishing white matter

MOBP levels are regulated by Fyn kinase and affect the morphological differentiation of oligodendrocytes

<em>In Vivo</em> Gene Transfer to Schwann Cells in the Rodent Sciatic Nerve by Electroporation

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