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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Vydáno v:eLife Ročník 8
Hlavní autoři: Swire, Matthew, Kotelevtsev, Yuri, Webb, David J, Lyons, David A, ffrench-Constant, Charles
Médium: Journal Article
Jazyk:angličtina
Vydáno: England eLife Science Publications, Ltd 28.10.2019
eLife Sciences Publications Ltd
eLife Sciences Publications, Ltd
Témata:
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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Abstract 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.
AbstractList 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.
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.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.
Audience Academic
Author Webb, David J
Kotelevtsev, Yuri
ffrench-Constant, Charles
Swire, Matthew
Lyons, David A
Author_xml – sequence: 1
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  orcidid: 0000-0003-4294-4926
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  organization: MRC Centre for Regenerative Medicine, MS Society Edinburgh Centre, University of Edinburgh, Edinburgh, United Kingdom, Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
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  surname: Kotelevtsev
  fullname: Kotelevtsev, Yuri
  organization: Centre for Neurobiology and Brain Restoration, Skoltech Institute for Science and Technology, Moscow, Russian Federation
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  fullname: Webb, David J
  organization: British Heart Foundation Centre of Research Excellence, Centre of Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
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  orcidid: 0000-0003-1166-4454
  surname: Lyons
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  organization: Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
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  surname: ffrench-Constant
  fullname: ffrench-Constant, Charles
  organization: MRC Centre for Regenerative Medicine, MS Society Edinburgh Centre, University of Edinburgh, Edinburgh, United Kingdom
BackLink https://www.ncbi.nlm.nih.gov/pubmed/31657718$$D View this record in MEDLINE/PubMed
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Keywords endothelin
mouse
rat
neuroscience
myelination
oligodendrocytes
zebrafish
Language English
License http://creativecommons.org/licenses/by/4.0
2019, Swire et al.
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Snippet Experience and changes in neuronal activity can alter CNS myelination, but the signalling pathways responsible remain poorly understood. Here we define a...
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SourceType Open Website
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SubjectTerms 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
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