Aspartate racemase, generating neuronal D-aspartate, regulates adult neurogenesis

Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3175-9. doi: 10.1073/pnas.0914706107. Epub 2010 Jan 26.

Abstract

D-aspartic acid is abundant in the developing brain. We have identified and cloned mammalian aspartate racemase (DR), which converts L-aspartate to D-aspartate and colocalizes with D-aspartate in the brain and neuroendocrine tissues. Depletion of DR by retrovirus-mediated expression of short-hairpin RNA in newborn neurons of the adult hippocampus elicits profound defects in the dendritic development and survival of newborn neurons and survival. Because D-aspartate is a potential endogenous ligand for NMDA receptors, the loss of which elicits a phenotype resembling DR depletion, D-aspartate may function as a modulator of adult neurogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Isomerases / genetics
  • Amino Acid Isomerases / metabolism*
  • Animals
  • Blotting, Western
  • Cloning, Molecular
  • D-Aspartic Acid / biosynthesis*
  • Female
  • Genetic Vectors / genetics
  • Hippocampus / metabolism*
  • Immunohistochemistry
  • Inverted Repeat Sequences / genetics
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Neurogenesis / physiology*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Retroviridae
  • Stem Cells / metabolism

Substances

  • Receptors, N-Methyl-D-Aspartate
  • D-Aspartic Acid
  • Amino Acid Isomerases
  • aspartate racemase