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d-Serine Regulates Proliferation and Neuronal Differentiation of Neural Stem Cells from Postnatal Mouse Forebrain.
- Source :
-
CNS Neuroscience & Therapeutics . Jan2012, Vol. 18 Issue 1, p4-13. 10p. - Publication Year :
- 2012
-
Abstract
- SUMMARY Background and purpose: d-Serine, the endogenous co-agonist of N-methyl- d-aspartate (NM dA) 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 Ca2+ 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17555930
- Volume :
- 18
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- CNS Neuroscience & Therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 70607124
- Full Text :
- https://doi.org/10.1111/j.1755-5949.2011.00276.x