Neuronal activity regulates remyelination via glutamate signalling to oligodendrocyte progenitors

Hélène O. B. Gautier, Kimberley A. Evans, Katrin Volbracht, Rachel James, Sergey Sitnikov, Iben Lundgaard, Fiona James, Cristina Lao-Peregrin, Richard Reynolds, Robin J. M. Franklin and Ragnhildur T Káradóttir ()
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Hélène O. B. Gautier: University of Cambridge
Kimberley A. Evans: University of Cambridge
Katrin Volbracht: University of Cambridge
Rachel James: Faculty of Medicine, Imperial College London, Hammersmith Hospital
Sergey Sitnikov: University of Cambridge
Iben Lundgaard: University of Cambridge
Fiona James: University of Cambridge
Cristina Lao-Peregrin: University of Cambridge
Richard Reynolds: Faculty of Medicine, Imperial College London, Hammersmith Hospital
Robin J. M. Franklin: University of Cambridge
Ragnhildur T Káradóttir: University of Cambridge

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: 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: 2015
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DOI: 10.1038/ncomms9518

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