Journal
CNS NEUROSCIENCE & THERAPEUTICS
Volume 18, Issue 1, Pages 4-13Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1755-5949.2011.00276.x
Keywords
Differentiation; d-Serine; Neural stem cell; N-methyl-d-aspartate; Proliferation
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Funding
- National Key Basic Research Program of China [2009CB521906, 2011CB504100]
- National Natural Science Foundation of China [81030060, 30973517]
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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 Ca2+ transient, and thereby, inhibited the phosphorylation of glycogen synthase kinase3 beta (GSK3 beta), 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.
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