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3236724 
Journal Article 
Role of nitric oxide in the regulation of neuronal proliferation, survival and differentiation 
Contestabile, A; Ciani, E 
2004 
1 
Neurochemistry International
ISSN: 0197-0186
EISSN: 1872-9754 
45 
6 
903-914 
WOS:000223234600014 
Nitric oxide (NO), an important cellular messenger, has
been linked to both neurodegenerative and neuroprotective actions. In the present review, we
focus on recent data establishing a survival and differentiation role for NO in several neural in
vitro and in vivo models. Nitric oxide has been found to be essential for survival of neuronal
cell lines and primary neurons in culture under various death challenges. Furthermore, its lack
may aggravate some neuropathological conditions in experimental animals. Several cellular
pathways and signaling systems subserving this neuroprotective role of NO are considered in the
review. Survey of recent data related to the developmental role of NO mainly focus on its action
as a negative regulator of neuronal precursor cells proliferation and on its role of promotion of
neuronal differentiation. Discussion on discrepancies arising from the literature is focused on
the Janus-faced properties of the molecule and it is proposed that most controversial results are
related to the intrinsic property of NO to compensate among functionally opposed effects. As an
example, the increased proliferation of neural cell precursors under conditions of NO shortage
may be, later on in the development, compensated by increased elimination through programmed cell
death as a consequence of the lack of the survival-promoting action of the molecule. To elucidate
these complex, and possibly contrasting, effects of NO is indicated as an important task for
future researches. (C) 2004 Published by Elsevier Ltd. 
nitric oxide; neurogenesis; survival; apoptosis; neurodegeneration; neuroprotection