NMDA receptors are expressed in oligodendrocytes and activated in ischaemia
By R. Káradóttir, P. Cavelier, L. Bergersen, David Attwell. Nature, 2005
760 citations recorded by the source corpus.
Glutamate-mediated damage to oligodendrocytes contributes to mental or physical impairment in periventricular leukomalacia (pre- or perinatal white matter injury leading to cerebral palsy), spinal cord injury, multiple sclerosis and stroke. Unlike neurons, white matter oligodendrocytes reportedly lack NMDA (N-methyl-d-aspartate) receptors. It is believed that glutamate damages oligodendrocytes, especially their precursor cells, by acting on calcium-permeable AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)/kainate receptors alone or by reversing cystine–glutamate exchange and depriving cells of antioxidant protection. Here we show that precursor, immature and mature oligodendrocytes in the white matter of the cerebellum and corpus callosum exhibit NMDA-evoked currents, mediated by receptors that are blocked only weakly by Mg2+ and that may contain NR1, NR2C and NR3 NMDA receptor subunits. NMDA receptors are present in the myelinating processes of oligodendrocytes, where the small intracellular space could lead to a large rise in intracellular ion concentration in response to NMDA receptor activation. Simulating ischaemia led to development of an inward current in oligodendrocytes, which was partly mediated by NMDA receptors. These results point to NMDA receptors of unusual subunit composition as a potential therapeutic target for preventing white matter damage in a variety of diseases.
Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Pediatrics, Perinatology and Child Health
View Paper: https://www.semanticscholar.org/paper/17f4fd34700a00d7cf127da313f0d2a299e5b646
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In Cellular and Molecular Neuroscience
In Developmental Neuroscience
Citations in the corpus
- Neurotransmitter-Triggered Transfer of Exosomes Mediates Oligodendrocyte–Neuron Communication (2013, background): “Mg block [31], which in neurons is released by AMPA receptor activation.”
- Neuronal activity-dependent control of postnatal neurogenesis and gliogenesis (2018, neutral): “OPCs receive synaptic inputs from axons in both gray (Bergles et al. 2000, Jabs et al. 2005, Lin & Bergles 2004) and white matter (Káradóttir et al. 2005, 2008; Kukley et al. 2007; Ziskin et al. 2007).”
- The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. (2006, background): “Recent work shows NMDA receptor (NMDAR) expression and function in oligodendrocytes (Salter and Fern, 2005; Karadottir et al., 2005).”
- Myelination and support of axonal integrity by glia (2010, background): “, much recent work has been devoted to the role of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) and NMDA ( N -methyl- D -aspartate) type glutamate receptors on NG2 cells and myelinating oligodendrocyte”
- Electrical and synaptic integration of glioma into neural circuits (2019, neutral): “2c), the only glial cell type that normally functions as a post-synaptic cell 3,4 .”
- Glutamate Receptor Ion Channels: Structure, Regulation, and Function (2010, background): “Unique NMDA receptors have been identified on oligodendrocytes (Káradóttir et al., 2005; Salter and Fern, 2005; Micu et al., 2006; Stys and Lipton, 2007), and it is unclear whether inhibition of these receptors is sufficient to prevent ischemia-induced white matter loss (Baltan et al.”