Review Dual role of nitric oxide in adult neurogenesis Antonio Ca ´rdenas * , Marı ´a A. Moro, Olivia Hurtado, Juan C. Leza, Ignacio Lizasoain Instituto de Farmacologı ´a y Toxicologı ´a del CSIC, Departamento de Farmacologı ´a, Facultad de Medicina, Universidad Complutense de Madrid, Av. Complutense s/n, 28040 Madrid, Spain Accepted 23 March 2005 Available online 20 April 2005 Abstract In the last decade, it has been demonstrated that neurogenesis persists in the adult mammalian brain and that it is induced after insults, where newborn neurons migrate to damaged areas, differentiate and contribute to the recovery. The understanding of the cellular and molecular events involved in this phenomenon could provide effective therapies not only to promote brain repair in stroke or seizures, but also to facilitate functional improvement in depression or Alzheimer. In this context, many advances have been made, such as the implication of different growth factors, membrane receptors, and most importantly diffusible messengers like nitric oxide (NO). We review here studies in both normal and pathophysiological conditions that suggest a dual role for NO in adult neurogenesis and its relation to different pharmacological strategies stimulating neurogenesis. D 2005 Elsevier B.V. All rights reserved. Theme: Development and regeneration Topic: Genesis of neurons and glia Keywords: Neurogenesis; NO; Stroke; Seizure; Depression; Alzheimer Contents 1. Introduction ............................................................ 1 2. Neurogenesis ........................................................... 2 2.1. Tissue localization ..................................................... 2 2.2. Regulation of neurogenesis ................................................ 2 2.3. Phases ........................................................... 2 3. NO and neurogenesis ....................................................... 3 4. Conclusion ............................................................ 3 Acknowledgments ........................................................... 4 References ............................................................... 4 1. Introduction The formation of new neurons or neurogenesis is an important phenomenon implicated in the development of the nervous system; in the last years, it has been demonstrated that neurogenesis also occurs in the adult nervous system [17], and that it can be induced after brain injuries such as seizures or stroke [36,51]. The discovery of the adult neurogenesis has been considered as a possible new facet of recovery that may translate into new treatments for stroke [48]; in addition, its inhibition has been recently suggested to be involved in the pathogenesis of depression and Alzheimer [57,62], and different studies exist about its 0165-0173/$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.brainresrev.2005.03.006 * Corresponding author. Fax: +34 91 3941463. E-mail address: acardenas@ift.csic.es (A. Ca ´rdenas). Brain Research Reviews 50 (2005) 1 – 6 www.elsevier.com/locate/brainresrev