Myelination by oligodendrocytes facilitates rapid nerve conduction. Loss of oligodendrocytes and failure of myelination lead to
nerve degeneration and numerous demyelinating
white matter diseases.
N-methyl-D-aspartate (
NMDA) receptors, which are key regulators on neuron survival and functions, have been recently identified to express in oligodendrocytes, especially in the myelin sheath.
NMDA receptor signaling in oligodendrocytes plays crucial roles in energy metabolism and myelination. In the present review, we highlight the subcellular location-specific impairment of excessive
NMDA receptor signaling on oligodendrocyte energy metabolism in
soma and myelin, and the mechanisms including Ca(2+) overload, acidotoxicity,
mitochondria dysfunction, and impairment of respiratory chains. Conversely, physiological
NMDA receptor signaling regulates differentiation and migration of oligodendrocytes. How can we use above knowledge to treat excitotoxic oligodendrocyte loss, congenital myelination deficiency, or postnatal
demyelination? A thorough understanding of
NMDA receptor signaling-mediated cellular events in oligodendrocytes at the pathophysiological level will no doubt aid in exploring effective therapeutic strategies for demyelinating
white matter diseases.