Neuregulin and BDNF induce a switch to NMDA receptor dependent myelination by oligodendrocytes

Myelin, produced by oligodendrocytes, is essential for normal brain function, as it ensures fast neuronal communication. However, what determines whether an individual neuronal axon becomes myelinated remains unknown. Here we show that there are two distinct modes of myelination, one that is independent of neuronal activity and the release of the neurotransmitter glutamate, and another that depends on axons releasing glutamate to activate NMDA receptors on oligodendrocytes. Neuregulin switches oligodendrocytes from the activity-independent to the activity-dependent mode of myelination: by increasing oligodendrocyte lineage cells’ sensitivity to glutamate. Thus, a neuregulin-controlled switch enhances the myelination of active axons. Furthermore we demonstrate that remyelination after white matter damage (as occurs in diseases like spinal cord injury and multiple sclerosis) is NMDA receptor-dependent. These data help us understand the signalling regulating myelination, and suggest novel roles for neuregulin in schizophrenia and in remyelination after white matter damage.

 

Lundgaard I, Luzhynskaya A, Stockley JH, Wang Z, Evans KA, Swire M, Volbracht K, Gautier HO, Franklin RJ, Ffrench-Constant C, Attwell D, Káradóttir RT. Neuregulin and BDNF Induce a Switch to NMDA Receptor-Dependent Myelination by Oligodendrocytes. PLoS Biology. PMID: 24391468

Full article in PLoS Biology

Image

OPCs plated on DRG neuron axons (red) terminally differentiate into mature oligodendrocytes (green) that myelinate the neuronal axons.

Iben Lundgaard

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