Nitric oxide negatively regulates proliferation and promotes neuronal differentiation through N-Myc downregulation

Ciani, Elisabetta; Severi, S; Contestabile, Andrea; Bartesaghi, Renata; Contestabile, Antonio

doi:10.1242/jcs.01348

Cited by 61 publications

(68 citation statements)

References 77 publications

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“…In embryos, NO inhibits neural precursor cell division and promotes neuronal differentiation in developing Drosophila imaginal disks (Kuzin et al, 1996) and Xenopus tadpole optic tectum (Peunova et al, 2001). A similar antiproliferative effect of NO has been reported in vitro in mammalian tumoral cell lines of neural origin (MurilloCarretero et al, 2002;Obregon et al, 1997;Peunova and Enikolopov, 1995;Phung et al, 1999) and in neuronal precursors isolated from the embryonic (Cheng et al, 2003) and neonatal (Ciani et al, 2004) brain. Additionally, several groups have shown that NO is a negative regulator of neurogenesis in the adult SVZ.…”

Section: Indexing Terms: Egf Receptor; Neural Stem Cells; Neurogenesisupporting

confidence: 58%

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

Romero‐Grimaldi

Moreno‐López

Estrada

2007

J of Comparative Neurology

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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.

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Section: Indexing Terms: Egf Receptor; Neural Stem Cells; Neurogenesisupporting

confidence: 58%

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

Romero‐Grimaldi

Moreno‐López

Estrada

2007

J of Comparative Neurology

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“…It has been previously demonstrated that NO acts as an important negative regulator of cell proliferation in the adult mammalian brain [41,42]. A similar anti-proliferative effect of NO has been reported in neuronal precursors isolated from the embryonic [43] and neonatal [44] brain. The observed early appearance of nitrergic cells in the RMS indicates an association between NO production and decreased proliferation induced by maternal deprivation.…”

Section: Discussionsupporting

confidence: 66%

Early stress affects neurogenesis in the rat rostral migratory stream

et al. 2010

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Early stress affects neurogenesis in the rat rostral migratory stream Abstract: Stressful experience during the early postnatal period may influence processes associated with neurogenesis (i.e. proliferation, cell death, appearance of astrocytes or cell differentiation) in the neonatal rat rostral migratory stream (RMS). To induce stress, pups were subjected to maternal deprivation daily for three hours, starting from the first postnatal day till the seventh postnatal day. Immunohistochemical methods were used to visualize proliferating cells and astrocytes; dying cells and nitrergic cells were visualizedusinghistochemicalstaining.Quantitativeanalysisshowedthatmaternaldeprivationdecreasedthenumberofproliferating cells and significantly increased the number of dying cells in the RMS. Maternal deprivation did not influence the appearance of astrocytes in the RMS, but caused premature differentiation of nitrergic cells. In control rats, nitrergic cells can be observed in the RMS as early as the tenth postnatal day. In maternally deprived pups, these cells were detected as early as the seventh postnatalday. TheobservedearlierappearanceofnitrergiccellsintheRMSwasassociatedwithalteredproliferationandincreased cell dying and this observation supports the hypothesis that nitric oxide has an anti-proliferative role in the RMS. Our study demonstrates that maternal deprivation represents a stressful condition with a profound impact on early postnatal neurogenesis.

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“…In addition, the proneural basic helix-loop-helix (bHLH) transcription factor neurogenin 1 (Ngn1) promotes neuronal differentiation and suppresses formation of astrocytes (Sauvageot and Stiles, 2002). NO regulates synaptic remodeling and neuronal differentiation in the adult mammal CNS (Bicker, 2001;Ciani et al, 2004;Seidel and Bicker, 2000;Sunico et al, 2005;Truman et al, 1996). We, therefore, hypothesize, DETA-NONOate upregulates the Ncadherin/β-catenin pathway and Ngn1 expression and thereby promotes neurogenesis in both young and older rats.…”

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confidence: 99%

N-cadherin mediates nitric oxide-induced neurogenesis in young and retired breeder neurospheres

Chen

Zacharek

et al. 2006

Neuroscience

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Neurogenesis may contribute to functional recovery after neural injury. Nitric oxide donors such as DETA-NONOate promote functional recovery after stroke. However, the mechanisms underlying functional improvement have not been ascertained. We therefore investigated the effects of DETANONOate on neural progenitor/stem cell neurospheres derived from the subventricular zone from young and retired breeder rat brain. Subventricular zone cells were dissociated from normal young adult male Wistar rats (2-3 months old) and retired breeder rats (14 months old), treated with or without DETA-NONOate. Subventricular zone neurosphere formation, proliferation, telomerase activity, and Neurogenin 1 mRNA expression were significantly decreased and glial fibrillary acidic protein expression was significantly increased in subventricular zone neurospheres from retired breeder rats compared with young rats. Treatment of neurospheres with DETA-NONOate significantly decreased neurosphere formation and telomerase activity, and promoted neuronal differentiation and neurite outgrowth concomitantly with increased N-cadherin and β-catenin mRNA expression in both young and old neurospheres. DETA-NONOate selectively increased Neurogenin 1 and decreased glial fibrillary acidic protein mRNA expression in retired breeder neurospheres. Ncadherin significantly increased Neurogenin 1 mRNA expression in young and old neurospheres. Anti-N-cadherin reversed DETA-NONOate-induced neurosphere adhesion, neuronal differentiation, neurite outgrowth, and β-catenin mRNA expression. Our data indicate that age has a potent effect on the characteristics of subventricular zone neurospheres; neurospheres from young rats show significantly higher formation, proliferation and telomerase activity than older neurospheres. In contrast, older neurospheres exhibit significantly increased glial differentiation than young neurospheres. DETA-NONOate promotes neuronal differentiation and neurite outgrowth in both young and older neurospheres. The molecular mechanisms associated with the DETANONOate modulation of neurospheres from young and older animals as well age dependent effects of neurospheres appear to be controlled by N-cadherin and β-catenin gene expression, which subsequently regulates the neuronal differentiating factor Neurogenin expression in both young and old neural progenitor cells. Neural precursor cells contribute to adult neurogenesis and to the limited attempt of brain repair after injury. Induction of self-renewal or differentiation of neural progenitor cells depends on the interaction of intrinsic and environmental cues. Age is an intrinsic factor, which may influence neurogenesis. However, neurogenesis, which contributes to the ability of the adult brain to function normally and adapt to disease, declines with advancing age (Cameron and McKay, 1999;Kuhn et al., 1996). In addition, accelerated glial reactivity in aged rats also correlates with reduced functional recovery after stroke (Badan et al., 2003a). Glial reactivity increases with age, w...

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Nitric oxide negatively regulates proliferation and promotes neuronal differentiation through N-Myc downregulation

Cited by 61 publications

References 77 publications

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

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

Early stress affects neurogenesis in the rat rostral migratory stream

N-cadherin mediates nitric oxide-induced neurogenesis in young and retired breeder neurospheres

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