Neuronal activity regulates remyelination via glutamate signalling to oligodendrocyte progenitors
Author(s)
Type
Journal Article
Abstract
Myelin regeneration can occur spontaneously in demyelinating diseases such as multiple sclerosis (MS). However, the underlying mechanisms and causes of its frequent failure remain incompletely understood. Here we show, using an in-vivo remyelination model, that demyelinated axons are electrically active and generate de novo synapses with recruited oligodendrocyte progenitor cells (OPCs), which, early after lesion induction, sense neuronal activity by expressing AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)/kainate receptors. Blocking neuronal activity, axonal vesicular release or AMPA receptors in demyelinated lesions results in reduced remyelination. In the absence of neuronal activity there is a ~6-fold increase in OPC number within the lesions and a reduced proportion of differentiated oligodendrocytes. These findings reveal that neuronal activity and release of glutamate instruct OPCs to differentiate into new myelinating oligodendrocytes that recover lost function. Co-localization of OPCs with the presynaptic protein VGluT2 in MS lesions implies that this mechanism may provide novel targets to therapeutically enhance remyelination.
Date Issued
2015-10-06
Date Acceptance
2015-08-30
Citation
Nature Communications, 2015, 6
ISSN
2041-1723
Publisher
Nature Publishing Group: Nature Communications
Journal / Book Title
Nature Communications
Volume
6
Copyright Statement
© The Author(s) 2015. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise
in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material.
To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
article are included in the article’s Creative Commons license, unless indicated otherwise
in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material.
To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Sponsor
Parkinson's UK
Medical Research Council (MRC)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000364930800003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
J-1402
N/A
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CENTRAL-NERVOUS-SYSTEM
MULTIPLE-SCLEROSIS
PRECURSOR CELLS
WHITE-MATTER
AUTOIMMUNE ENCEPHALOMYELITIS
PROTEOLIPID PROTEIN
CNS DEMYELINATION
CORPUS-CALLOSUM
SODIUM-CHANNELS
NMDA RECEPTORS
Multidisciplinary
Publication Status
Published
Article Number
8518