Targeted disruption of serine racemase affects glutamatergic neurotransmission and behavior

A. C. Basu, G. E. Tsai, C. L. Ma, J. T. Ehmsen, A. K. Mustafa, L. Han, Z. I. Jiang, M. A. Benneyworth, M. P. Froimowitz, N. Lange, S. H. Snyder, R. Bergeron, J. T. Coyle

Research output: Contribution to journalArticle

Abstract

A subset of glutamate receptors that are specifically sensitive to the glutamate analog N-methyl-D-aspartate (NMDA) are molecular coincidence detectors, necessary for activity-dependent processes of neurodevelopment and in sensory and cognitive functions. The activity of these receptors is modulated by the endogenous amino acid D-serine, but the extent to which D-serine is necessary for the normal development and function of the mammalian nervous system was previously unknown. Decreased signaling at NMDA receptors has been implicated in the pathophysiology of schizophrenia based on pharmacological evidence, and several human genes related to D-serine metabolism and glutamatergic neurotransmission have been implicated in the etiology of schizophrenia. Here we show that genetically modified mice lacking the ability to produce D-serine endogenously have profoundly altered glutamatergic neurotransmission, and relatively subtle but significant behavioral abnormalities that reflect hyperactivity and impaired spatial memory, and that are consistent with elevated anxiety.

Original languageEnglish (US)
Pages (from-to)719-727
Number of pages9
JournalMolecular psychiatry
Volume14
Issue number7
DOIs
StatePublished - Jul 2009

Keywords

  • D-serine
  • Glutamate
  • NMDA receptor
  • Schizophrenia

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Basu, A. C., Tsai, G. E., Ma, C. L., Ehmsen, J. T., Mustafa, A. K., Han, L., Jiang, Z. I., Benneyworth, M. A., Froimowitz, M. P., Lange, N., Snyder, S. H., Bergeron, R., & Coyle, J. T. (2009). Targeted disruption of serine racemase affects glutamatergic neurotransmission and behavior. Molecular psychiatry, 14(7), 719-727. https://doi.org/10.1038/mp.2008.130