NEUROBIOLOGY NMDA Receptors on Oligodendrocytes

Although it had been reported that oligodendrocytes, the myelinating glial cells of the central nervous system, do not have N-methyl-D-aspartate (NMDA)-type glutamate receptors, two groups (Káradóttir et al. and Salter and Fern) challenge this dogma. They show that a pharmacologically distinct form of NMDA receptor is indeed present on the processes and soma of oligodendrocytes. Káradóttir et al. show that precursor, immature, and mature oligodendrocytes in rat brain slices of the cerebellum or corpus callosum all respond to glutamate with an inward current and that this current was maximally inhibited by the addition of both NMDA- and -amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-type antagonists. Unlike neuronal NMDA receptors, the oligodendrocyte NMDA receptors were less susceptible to Mg²⁺ block. Ifendopril, which specifically blocks NMDA receptors with the NR2B subunit, had no effect on the oligodendrocyte NMDA-evoked current. Labeling experiments indicated that the oligodendrocyte processes contained the NR1, NR2C, and NR3 subunits. Ischemia evoked an inward current that was partially attributable to released glutamate and was blocked by NMDA and AMPA antagonists. Salter and Fern focused on the response of mouse optic nerve to oxygen and glucose deprivation (OGD), using mice in which the oligodendrocytes were visualized through expression of an oligodendrocyte-specific promoter-driven green fluorescent protein (GFP). OGD caused the loss of oligodendrocyte processes and detachment of the processes from adjacent membrane regions or the soma. Process loss and detachment was prevented if OGD was applied under conditions of low extracellular calcium or if an NMDA receptor blocker and an AMPA receptor blocker were coapplied. Clusters of NMDA NR1 subunits were detected on the oligodendrocyte processes, and immunofluorescence analysis and reverse transcription polymerase chain reaction (RT-PCR) analysis indicated that the oligodendrocytes expressed the NR1, NR2A, NR2B, NR2C, NR2D, and NR3A subunits. Thus, oligodendrocytes appear to have NMDA receptors with localization in the processes where activation of these receptors at times of stress may contribute to neurological disorders that involve defective or loss of myelination.

R. Káradóttir, P. Cavelier, L. H. Bergersen, D. Attwell, NMDA receptors are expressed in oligodendrocytes and activated in ischaemia. Nature 438, 1162-1166 (2005). [PubMed]

M. G. Salter, R. Fern, NMDA receptors are expressed in developing oligodendrocyte processes and mediate injury. Nature 438, 1167-1171 (2005). [PubMed]