title: Nitric oxide is a physiological inhibitor of neurogenesis in the adult mouse subventricular zone and olfactory bulb.
abstract: The subventricular zone of the rodent brain retains the capacity of generating new neurons in adulthood. The newly formed neuroblasts migrate rostrally toward the olfactory bulb, where they differentiate as granular and periglomerular interneurons. The reported presence of differentiated neurons expressing the neuronal isoform of nitric oxide synthase (NOS) in the periphery of the neurogenic region and the organization of their varicose axons as a network in which the precursors are immersed raised the hypothesis that endogenous nitric oxide (NO) may participate in the control of neurogenesis in the subventricular zone. Systemic administration of the NOS inhibitors N(omega)-nitro-L-arginine methyl ester or 7-nitroindazole to adult mice produced a dose- and time-dependent increase in the number of mitotic cells in the subventricular zone, rostral migratory stream, and olfactory bulb, but not in the dentate gyrus of the hippocampus, without affecting apoptosis. In the subventricular zone, this effect was exerted selectively on a precursor subpopulation expressing nestin but not neuronal or glial cell-specific proteins. In addition, in the olfactory bulb, analysis of maturation markers in the newly generated neurons indicated that chronic NOS inhibition caused a delay in neuronal differentiation. Postmitotic cell survival and migration were not affected when NO production was impaired. Our results suggest that NO, produced by nitrergic neurons in the adult mouse subventricular zone and olfactory bulb, exerts a negative control on the size of the undifferentiated precursor pool and promotes neuronal differentiation.
authors.affiliation: Area de Fisiología, Facultad de Medicina, Universidad de Cádiz, 11003 Cádiz, Spain.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Moreno-López
authors.forename: Carmen
authors.initials: C
authors.lastname: Romero-Grimaldi
authors.forename: José Angel
authors.initials: JA
authors.lastname: Noval
authors.forename: Maribel
authors.initials: M
authors.lastname: Murillo-Carretero
authors.forename: Esperanza R
authors.initials: ER
authors.lastname: Matarredona
authors.forename: Carmen
authors.initials: C
authors.lastname: Estrada
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement; D002470:Cell Survival; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D020547:Lateral Ventricles / Q000166:cytology*; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000166:cytology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009830:Olfactory Bulb / Q000166:cytology*; D013234:Stem Cells / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester