Age‐dependent effect of nitric oxide on subventricular zone and olfactory bulb neural precursor proliferation

Abstract

Nitric oxide (NO) synthase (NOS) is developmentally regulated in the embryonic brain, where NO participates in cell proliferation, survival, and differentiation. In adults, NO inhibits neurogenesis under physiological conditions. This work investigates whether the NO action is preserved all along development up to adulthood or whether its effects in adults are a new feature acquired during brain maturation. The relationship between nitrergic neurons and precursors, as well as the functional consequences of pharmacological NOS inhibition, were comparatively analyzed in the subventricular zone (SVZ) and olfactory bulb (OB) of postnatal (P7) and adult (>P60) mouse brains. The SVZ was markedly reduced between P7 and adults, and, at both ages, neurons expressing neuronal NOS (nNOS) were found in its striatal limits. In postnatal mice, these nitrergic neurons contained PSA-NCAM, and their projections were scarce, whereas, in adults, mature nitrergic neurons, devoid of PSA-NCAM, presented abundant neuropil. In the OB, local proliferation almost disappeared in the transition to adulthood, and periglomerular nitrergic neurons, some of which were PSA-NCAM positive, were found in postnatal and adult mice. Administration of the NOS inhibitor L-NAME did not affect cell proliferation in the SVZ or in the OB of postnatal mice, whereas it significantly enhanced the number of mitotic cells in both regions in adults. Thus, the NO action on SVZ neurogenesis is a phenomenon that appears after the postnatal age, which is probably due to the germinal layer size reduction, allowing exposure of the NO-sensitive neural precursors to the NO produced in the SVZ-striatum limits.

Interaction of Atoms with Grain Surfaces in Steel: Periodic Dependence of Binding Energy on Atomic Number and Influence on Wear Resistance

“…The process of neurogenesis is composed of three main steps, which include precursor proliferation, migration; differentiation, integration and survival. It has been demonstrated, that SVZ of mammals is surrounded by nNOS positive neurons [16], and cells expressing nNOS also have been identified in neuronal precursors in DG [17]. These findings suggest nNOS might take part in neurogenesis regulation.…”

From progenitors to integrated neurons: Role of neurotransmitters in adult olfactory neurogenesis

“…Although NO cannot be strictly categorized as a classical neurotransmitter, it is considered in this review based on release by presynaptic terminals in an activity-dependent manner. Close proximity between nitrergic neurons and neuronal progenitors has been described in the SVZ of both postnatal (P7) and adult mice (Moreno-Lopez et al, 2000;Romero-Grimaldi et al, 2008) suggesting an action of NO on SVZ niche. Interestingly, expression of nNOS differs in postnatal development and adult age (Romero-Grimaldi et al, 2008).…”

“…Close proximity between nitrergic neurons and neuronal progenitors has been described in the SVZ of both postnatal (P7) and adult mice (Moreno-Lopez et al, 2000;Romero-Grimaldi et al, 2008) suggesting an action of NO on SVZ niche. Interestingly, expression of nNOS differs in postnatal development and adult age (Romero-Grimaldi et al, 2008). Neuroblasts, identified by PSA-NCAM immunolabeling, never express nNOS in the adult SVZ whereas PSA-NCAM partially overlaps with nNOS in postnatal SVZ (Romero-Grimaldi et al, 2008).…”

“…Interestingly, expression of nNOS differs in postnatal development and adult age (Romero-Grimaldi et al, 2008). Neuroblasts, identified by PSA-NCAM immunolabeling, never express nNOS in the adult SVZ whereas PSA-NCAM partially overlaps with nNOS in postnatal SVZ (Romero-Grimaldi et al, 2008). In the OB, where new neurons finally integrate, colocalization of nNOS and PSA-NCAM is found in both postnatal and adult mice (Romero-Grimaldi et al, 2008), suggesting that while NO could have a paracrine effect in the adult SVZ, it may work in an autocrine manner in the OB.…”

“…NO action in the SVZ is also developmentally regulated. While prevention of NO synthesis does not affect postnatal SVZ cell proliferation, adult neuronal precursors in the SVZ are highly sensitive to nNOS inhibition (Romero-Grimaldi et al, 2008). In physiological conditions, endogenous NO negatively regulates adult SVZ cell proliferation and pharmacological inhibition of nNOS synthesis by L-NAME, 7-NI (7-nitroindazole) or its genetic inactivation, results in increased proliferation in the SVZ and consequently higher newborn cell density in the OB (Cheng et al, 2003;MorenoLopez et al, 2004;Packer et al, 2003;Romero-Grimaldi et al, 2006).…”