D-Serine as a putative glial neurotransmitter

Solomon H. Snyder, Asif K. Mustafa, Paul M. Kim

Research output: Contribution to journalArticle

Abstract

Abundant recent evidence favors a neurotransmitter/neuromodulator role for D-serine. D-serine is synthesized from L-serine by serine racemase in astrocytic glia that synapses, especially in regions of the brain that are enriched in NMDA-glutamate receptors. D-serine is more potent than glycine at activating the ‘glycine’ site of these receptors. Moreover, selective degradation of D-serine but not glycine by D-amino acid oxidase markedly reduces NMDA neurotransmission. D-serine appears to be released physiologically in response to activation by glutamate of AMPA-glutamate receptors on D-serine-containing glia. This causes glutamate-receptor-interacting protein, which binds serine racemase, to stimulate enzyme activity and D-serine release. Thus, glutamate triggers the release of D-serine so that the two amino acids can act together on postsynaptic NMDA receptors. D-serine also plays a role in neural development, being released from Bergmann glia to chemokinetically enhance the migration of granule cell cerebellar neurons from the external to the internal granular layer.

Original languageEnglish (US)
Pages (from-to)275-281
Number of pages7
JournalNeuron Glia Biology
Volume1
Issue number3
DOIs
Publication statusPublished - 2004

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Keywords

  • cx-amino-3-hydroxy1-5-methy1-4-isoxazolepropionate receptor
  • D-serine N-methyl-D-aspartate receptor
  • serine racemase

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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