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D-Serine regulates proliferation and neuronal differentiation of neural stem cells from postnatal mouse forebrain.

CNS neuroscience & therapeutics (2012-01-28)
Xu Huang, Hui Kong, Mi Tang, Ming Lu, Jian-Hua Ding, Gang Hu

D-Serine, the endogenous co-agonist of N-methyl-D-aspartate (NMDA) receptors, has been recognized as an important gliotransmitter in the mammalian brain. D-serine has been shown to prevent psychostimulant-induced decrease in hippocampal neurogenesis. However, the mechanism whereby D-serine regulates neurogenesis has not been fully characterized. Therefore, this study was designed to investigate the impacts of D-serine on the proliferation, migration, and differentiation of primary cultured neural stem cells (NSCs). Immunohistochemistry analysis revealed NSCs expressed D-serine as well as serine racemase (SR). Degradation of endogenous D-serine with D-amino acid oxidase (DAAO) significantly inhibited the proliferation and neuronal differentiation of NSCs, but failed to affect their radial migration. Reversely, addition of exogenous D-serine did not affect the proliferation and migration of NSCs, but promoted NSC differentiation into neurons. Furthermore, DAAO could suppress the amplitude of glutamate-induced Ca(2+) transient, and thereby, inhibited the phosphorylation of glycogen synthase kinase3β (GSK3β), extracellular signal-regulated kinases1/2 (ERK1/2), and cAMP-responsive element-binding protein (CREB). Our findings demonstrate for the first time that NSCs can synthesize D-serine and, thereby, promote themselves proliferation and neuronal differentiation, which may afford a novel therapeutic strategy for the neurological disorders that require nerve cell replenishment, such as neurodegenerative diseases and stroke.

Product Number
Product Description

Anti-Nestin Antibody, clone rat-401, clone rat-401, Chemicon®, from mouse
Sodium benzoate, BioXtra, ≥99.5%
Sodium benzoate, ReagentPlus®, 99%
Sodium benzoate, purum p.a., ≥99.0% (NT)
Anti-BrdU Antibody, clone BU-1, culture supernatant, clone BU-1, Chemicon®
Sodium benzoate, Pharmaceutical Secondary Standard; Certified Reference Material
Sodium benzoate, puriss., meets analytical specification of Ph. Eur., BP, FCC, E211, 99.0-100.5% (calc. to the dried substance), powder