1. D-Serine regulates proliferation and neuronal differentiation of neural stem cells from postnatal mouse forebrain.
- Author
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Huang X, Kong H, Tang M, Lu M, Ding JH, and Hu G
- Subjects
- Analysis of Variance, Animals, Animals, Newborn, Bromodeoxyuridine metabolism, CREB-Binding Protein metabolism, Calcium metabolism, Cell Differentiation drug effects, Cell Movement physiology, Cells, Cultured, Chromatography, High Pressure Liquid, Culture Media, Conditioned chemistry, Dizocilpine Maleate pharmacology, Dose-Response Relationship, Drug, Enzyme Inhibitors pharmacology, Excitatory Amino Acid Antagonists pharmacology, MAP Kinase Kinase Kinases metabolism, Male, Mice, Serine pharmacology, Signal Transduction drug effects, Signal Transduction physiology, Sodium Benzoate pharmacology, Cell Differentiation physiology, Cell Proliferation drug effects, Neural Stem Cells metabolism, Prosencephalon cytology, Serine metabolism
- Abstract
Background and Purpose: 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)., Methods and Results: 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)., Conclusions: 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., (© 2012 Blackwell Publishing Ltd.)
- Published
- 2012
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