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Neuregulin and BDNF Induce a Switch to NMDA Receptor-Dependent Myelination by Oligodendrocytes

Lundgaard, Iben LU ; Luzhynskaya, Aryna ; Stockley, John H. ; Wang, Zhen ; Evans, Kimberley A. ; Swire, Matthew ; Volbracht, Katrin ; Gautier, Hélène O.B. ; Franklin, Robin J.M. and ffrench-Constant, Charles , et al. (2013) In PLoS Biology 11(12).
Abstract

Myelination is essential for rapid impulse conduction in the CNS, but what determines whether an individual axon becomes myelinated remains unknown. Here we show, using a myelinating coculture system, that there are two distinct modes of myelination, one that is independent of neuronal activity and glutamate release and another that depends on neuronal action potentials releasing glutamate to activate NMDA receptors on oligodendrocyte lineage cells. Neuregulin switches oligodendrocytes from the activity-independent to the activity-dependent mode of myelination by increasing NMDA receptor currents in oligodendrocyte lineage cells 6-fold. With neuregulin present myelination is accelerated and increased, and NMDA receptor block reduces... (More)

Myelination is essential for rapid impulse conduction in the CNS, but what determines whether an individual axon becomes myelinated remains unknown. Here we show, using a myelinating coculture system, that there are two distinct modes of myelination, one that is independent of neuronal activity and glutamate release and another that depends on neuronal action potentials releasing glutamate to activate NMDA receptors on oligodendrocyte lineage cells. Neuregulin switches oligodendrocytes from the activity-independent to the activity-dependent mode of myelination by increasing NMDA receptor currents in oligodendrocyte lineage cells 6-fold. With neuregulin present myelination is accelerated and increased, and NMDA receptor block reduces myelination to far below its level without neuregulin. Thus, a neuregulin-controlled switch enhances the myelination of active axons. In vivo, we demonstrate that remyelination after white matter damage is NMDA receptor-dependent. These data resolve controversies over the signalling regulating myelination and suggest novel roles for neuregulin in schizophrenia and in remyelination after white matter damage.

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publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS Biology
volume
11
issue
12
article number
e1001743
publisher
Public Library of Science (PLoS)
external identifiers
  • scopus:84892689677
  • pmid:24391468
ISSN
1545-7885
DOI
10.1371/journal.pbio.1001743
language
English
LU publication?
no
id
4d69830a-4f82-40a3-ae01-8549a6561447
date added to LUP
2019-05-16 16:50:16
date last changed
2024-06-11 11:55:26
@article{4d69830a-4f82-40a3-ae01-8549a6561447,
  abstract     = {{<p>Myelination is essential for rapid impulse conduction in the CNS, but what determines whether an individual axon becomes myelinated remains unknown. Here we show, using a myelinating coculture system, that there are two distinct modes of myelination, one that is independent of neuronal activity and glutamate release and another that depends on neuronal action potentials releasing glutamate to activate NMDA receptors on oligodendrocyte lineage cells. Neuregulin switches oligodendrocytes from the activity-independent to the activity-dependent mode of myelination by increasing NMDA receptor currents in oligodendrocyte lineage cells 6-fold. With neuregulin present myelination is accelerated and increased, and NMDA receptor block reduces myelination to far below its level without neuregulin. Thus, a neuregulin-controlled switch enhances the myelination of active axons. In vivo, we demonstrate that remyelination after white matter damage is NMDA receptor-dependent. These data resolve controversies over the signalling regulating myelination and suggest novel roles for neuregulin in schizophrenia and in remyelination after white matter damage.</p>}},
  author       = {{Lundgaard, Iben and Luzhynskaya, Aryna and Stockley, John H. and Wang, Zhen and Evans, Kimberley A. and Swire, Matthew and Volbracht, Katrin and Gautier, Hélène O.B. and Franklin, Robin J.M. and ffrench-Constant, Charles and Attwell, David and Káradóttir, Ragnhildur T.}},
  issn         = {{1545-7885}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{12}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS Biology}},
  title        = {{Neuregulin and BDNF Induce a Switch to NMDA Receptor-Dependent Myelination by Oligodendrocytes}},
  url          = {{http://dx.doi.org/10.1371/journal.pbio.1001743}},
  doi          = {{10.1371/journal.pbio.1001743}},
  volume       = {{11}},
  year         = {{2013}},
}