title: D-Serine regulates proliferation and neuronal differentiation of neural stem cells from postnatal mouse forebrain.
abstract: OBJECTIVE
  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).
  
  
  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.
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Jiangsu, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Huang
authors.forename: Hui
authors.initials: H
authors.lastname: Kong
authors.forename: Mi
authors.initials: M
authors.lastname: Tang
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Ding
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D017077:Culture Media, Conditioned / Q000737:chemistry; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008297:Male; D051379:Mice; D058953:Neural Stem Cells / Q000378:metabolism*; D016548:Prosencephalon / Q000166:cytology*; D012694:Serine / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020160:Sodium Benzoate / Q000494:pharmacology
chemical_list: D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D012694:Serine; D016291:Dizocilpine Maleate; D050882:CREB-Binding Protein; D020930:MAP Kinase Kinase Kinases; D001973:Bromodeoxyuridine; D020160:Sodium Benzoate; D002118:Calcium