Endothelin signalling mediates experience-dependent myelination in the CNS

Experience and changes in neuronal activity can alter CNS myelination, but the signalling pathways responsible remain poorly understood. Here we define a pathway in which endothelin, signalling through the G protein-coupled receptor endothelin receptor B and PKC epsilon, regulates the number of myel...

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Vydané v:	eLife Ročník 8
Hlavní autori:	Swire, Matthew, Kotelevtsev, Yuri, Webb, David J, Lyons, David A, ffrench-Constant, Charles
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	England eLife Science Publications, Ltd 28.10.2019 eLife Sciences Publications Ltd eLife Sciences Publications, Ltd
Predmet:	Animals Cellular signal transduction Containers Deoxyribonucleic acid DNA Endothelin Endothelins Endothelins - metabolism G proteins Hypotheses Kinases Medical research Membrane proteins Mice Myelin Sheath - metabolism Myelination Neural circuitry Neurons Neuroscience Neurosciences Novels Observations Oligodendrocytes Oligodendroglia - metabolism Phenotypes Physiological aspects Prefrontal cortex Prefrontal Cortex - physiology Protein kinase C Protein Kinase C-epsilon - metabolism Receptor, Endothelin B - metabolism Signal Transduction Social interactions Social isolation Software Zebrafish United States United Kingdom > UK endothelin mouse rat neuroscience myelination oligodendrocytes zebrafish
ISSN:	2050-084X, 2050-084X
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Popis
Shrnutí:	Experience and changes in neuronal activity can alter CNS myelination, but the signalling pathways responsible remain poorly understood. Here we define a pathway in which endothelin, signalling through the G protein-coupled receptor endothelin receptor B and PKC epsilon, regulates the number of myelin sheaths formed by individual oligodendrocytes in mouse and zebrafish. We show that this phenotype is also observed in the prefrontal cortex of mice following social isolation, and is associated with reduced expression of vascular endothelin. Additionally, we show that increasing endothelin signalling rescues this myelination defect caused by social isolation. Together, these results indicate that the vasculature responds to changes in neuronal activity associated with experience by regulating endothelin levels, which in turn affect the myelinating capacity of oligodendrocytes. This pathway may be employed to couple the metabolic support function of myelin to activity-dependent demand and also represents a novel mechanism for adaptive myelination.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2050-084X 2050-084X
DOI:	10.7554/eLife.49493