Ragnhildur Þóra Káradóttir
Remyelination requires neuronal activity, however the mechanisms underlying the interplay between remyelination and activity are poorly understood. Using a model of focal demyelination, we show that loss of myelin leads to a transient decline in neuronal activity and that preventing changes in activity following demyelination decreases the efficiency of remyelination. This transient decline in activity coincides with the peak of oligodendrocyte precursor cell (OPC) proliferation in the remyelinating white matter and increasing activity during this period reduces the number of proliferating OPCs. Investigating on the mechanisms underlying changes in neuronal activity, we found that following demyelination, microglia numbers increase in the grey matter and that synaptic terminals are engulfed by activated microglia, resulting in grey matter synaptic loss. These changes are likely to be required for myelin regeneration, as remyelination levels are decreased when microglia are depleted in the grey matter. Taken together our data suggest that microglia activation in the grey matter followed by a transient decrease in neuronal activity play a relevant role in the regeneration of myelin in the white matter.
