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

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2010-02, Vol.107 (7), p.3175-3179
Main Authors: Kim, Paul M, Duan, Xin, Huang, Alex S, Liu, Cindy Y, Ming, Guo-li, Song, Hongjun, Snyder, Solomon H
Format: Article
Language:English
Subjects:
Adults
Amino Acid Isomerases - genetics
Amino Acid Isomerases - metabolism
Animals
Biological Sciences
Blotting, Western
Brain
Cell lines
Cloning, Molecular
D-Aspartic Acid - biosynthesis
Dentate gyrus
Enzymes
Female
Gene expression
Genetic Vectors - genetics
Genotype & phenotype
Hippocampus
Hippocampus - metabolism
Immunohistochemistry
Inverted Repeat Sequences - genetics
Mice
Mice, Inbred C57BL
Molecular Structure
N methyl D aspartate receptors
Neurogenesis
Neurogenesis - physiology
Neurons
PC12 cells
Receptors, N-Methyl-D-Aspartate - metabolism
Retroviridae
Ribonucleic acid
RNA
Stem Cells - metabolism
Tissues
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Description
Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0914706107