D-serine, an endogenous synaptic modulator: localization to astrocytes and glutamate-stimulated release.
Using an antibody highly specific for D-serine conjugated to glutaraldehyde, we have localized endogenous D-serine in rat brain. Highest levels of D-serine immunoreactivity occur in the gray matter of the cerebral cortex, hippocampus, anterior olfactory nucleus, olfactory tubercle, and amygdala. Localizations of D-serine immunoreactivity correlate closely with those of D-serine binding to the glycine modulatory site of the N-methyl-D-aspartate (NMDA) receptor as visualized by autoradiography and are inversely correlated to the presence of D-amino acid oxidase. D-Serine is enriched in process-bearing glial cells in neuropil with the morphology of protoplasmic astrocytes. In glial cultures of rat cerebral cortex, D-serine is enriched in type 2 astrocytes. The release of D-serine from these cultures is stimulated by agonists of non-NMDA glutamate receptors, suggesting a mechanism by which astrocyte-derived D-serine could modulate neurotransmission. D-Serine appears to be the endogenous ligand for the glycine site of NMDA receptors.
Schell
M J
MJ
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Molliver
M E
ME
Snyder
S H
SH
D000818:Animals; D000918:Antibody Specificity; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001345:Autoradiography; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D003605:D-Amino-Acid Oxidase / Q000032:analysis / Q000378:metabolism*; D018698:Glutamic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology; D008959:Models, Neurological; D009928:Organ Specificity; D051381:Rats; D012694:Serine / Q000032:analysis / Q000378:metabolism*; D013237:Stereoisomerism; D013569:Synapses / Q000502:physiology*; D013687:Telencephalon / Q000378:metabolism; D014316:Tritium
D014316:Tritium; D018698:Glutamic Acid; D012694:Serine; D003605:D-Amino-Acid Oxidase; D007608:Kainic Acid