Send to

Choose Destination
Nat Commun. 2015 Oct 6;6:8518. doi: 10.1038/ncomms9518.

Neuronal activity regulates remyelination via glutamate signalling to oligodendrocyte progenitors.

Author information

Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Veterinary Medicine, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
Faculty of Medicine, Division of Brain Sciences, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.
Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AH, UK.


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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center