D-Aspartate regulates melanocortin formation and function: Behavioral alterations in D-aspartate oxidase-deficient mice

Alex S. Huang, Anne Beigneux, Zachary M. Weil, Paul M. Kim, Mark E. Molliver, Seth Blackshaw, Randy J. Nelson, Stephen G. Young, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

Abstract

D-Aspartate, an abundant D-amino acid enriched in neuroendocrine tissues, can be degraded by D-aspartate oxidase (Ddo). To elucidate the function of D-aspartate, we generated mice with targeted deletion of Ddo (Ddo -/-) and observe massive but selective augmentations of D-aspartate in various tissues. The pituitary intermediate lobe, normally devoid of D-aspartate from endogenous Ddo expression, manifests pronounced increases of immunoreactive D-aspartate in Ddo -/- mice. Ddo -/- mice show markedly diminished synthesis and levels of pituitary proopiomelanocortin/α-MSH, associated with decreased melanocortin-dependent behaviors. Therefore, Ddo is the endogenous enzyme that degrades D-aspartate, and Ddo-enriched organs, low in D-aspartate, may represent areas of high turnover where D-aspartate may be physiologically important.

Original languageEnglish (US)
Pages (from-to)2814-2819
Number of pages6
JournalJournal of Neuroscience
Volume26
Issue number10
DOIs
StatePublished - Mar 8 2006

Keywords

  • Amino acid
  • Aspartate
  • Behavior
  • Knock-out mice
  • Neuroendocrine
  • Proopiomelanocortin (POMC)
  • Turnover

ASJC Scopus subject areas

  • Neuroscience(all)

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