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 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.
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Paul M
PM
Kim
Xin
X
Duan
Alex S
AS
Huang
Cindy Y
CY
Liu
Guo-li
GL
Ming
Hongjun
H
Song
Solomon H
SH
Snyder
D000591:Amino Acid Isomerases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D003001:Cloning, Molecular; D026603:D-Aspartic Acid / Q000096:biosynthesis*; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D055029:Inverted Repeat Sequences / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D055495:Neurogenesis / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012190:Retroviridae; D013234:Stem Cells / Q000378:metabolism
D016194:Receptors, N-Methyl-D-Aspartate; D026603:D-Aspartic Acid; D000591:Amino Acid Isomerases; C019749:aspartate racemase