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PMID: 7732010 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 9 ·1995-04-25 ·Pages 3948-52

Schell MJ, Molliver ME, Snyder SH

Abstract

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.

MeSH Terms
Animals Antibody Specificity Astrocytes/drug effects,physiology Autoradiography Brain/cytology,metabolism,physiology Cells, Cultured D-Amino-Acid Oxidase/analysis,metabolism Glutamic Acid/pharmacology Hippocampus/metabolism Immunohistochemistry Kainic Acid/pharmacology Models, Neurological Organ Specificity Rats Serine/analysis,metabolism Stereoisomerism Synapses/physiology Telencephalon/metabolism Tritium
Chemicals
Tritium Glutamic Acid Serine D-Amino-Acid Oxidase Kainic Acid
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Schell M J
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Molliver M E
Snyder S H
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.9.3948
Published
1995-04-25
Pages
3948-52
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC42079
Subset
IM
Grants
NIDA NIH HHS · DA00074 · United States
NIDA NIH HHS · DA00266 · United States
NIMH NIH HHS · MH18501 · United States
External Links
PubMed source DOI: 10.1073/pnas.92.9.3948 PMC Full Text View journal details
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