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Publication : Nitric oxide negatively regulates mammalian adult neurogenesis.

First Author  Packer MA Year  2003
Journal  Proc Natl Acad Sci U S A Volume  100
Issue  16 Pages  9566-71
PubMed ID  12886012 Mgi Jnum  J:99879
Mgi Id  MGI:3584095 Doi  10.1073/pnas.1633579100
Citation  Packer MA, et al. (2003) Nitric oxide negatively regulates mammalian adult neurogenesis. Proc Natl Acad Sci U S A 100(16):9566-71
abstractText  Neural progenitor cells are widespread throughout the adult central nervous system but only give rise to neurons in specific loci. Negative regulators of neurogenesis have therefore been postulated, but none have yet been identified as subserving a significant role in the adult brain. Here we report that nitric oxide (NO) acts as an important negative regulator of cell proliferation in the adult mammalian brain. We used two independent approaches to examine the function of NO in adult neurogenesis. In a pharmacological approach, we suppressed NO production in the rat brain by intraventricular infusion of an NO synthase inhibitor. In a genetic approach, we generated a null mutant neuronal NO synthase knockout mouse line by targeting the exon encoding active center of the enzyme. In both models, the number of new cells generated in neurogenic areas of the adult brain, the olfactory subependyma and the dentate gyrus, was strongly augmented, which indicates that division of neural stem cells in the adult brain is controlled by NO and suggests a strategy for enhancing neurogenesis in the adult central nervous system.
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