D-serine, an endogenous synaptic modulator: Localization to astrocytes and glutamate-stimulated release

Michael John Schell, Mark E. Molliver, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

704 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3948-3952
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number9
StatePublished - Apr 25 1995


  • D-amino acid oxidase
  • N-methyl-D-aspartate
  • colloidal gold
  • glycine site
  • kainate

ASJC Scopus subject areas

  • General


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