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.