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This Article Free via Open Access: OA OA Full Text Full Text (PDF) Supplemental Data OA All Versions of this Article: 2005-0640v1 24/12/2792    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Covacu, R. Articles by Brundin, L. Search for Related Content PubMed PubMed Citation Articles by Covacu, R. Articles by Brundin, L.

TISSUE-SPECIFIC STEM CELLS

Nitric Oxide Exposure Diverts Neural Stem Cell Fate from Neurogenesis Towards Astrogliogenesis

^aDepartment of Clinical Neuroscience, Division of Neurology, Neuroimmunology Unit,
^bDepartment of Molecular Medicine and Surgery, Division of Urology,
^cDepartment of Neurosurgery, Karolinska Institutet, Stockholm, Sweden;
^dBaxter Laboratory in Genetic Pharmacology, Stanford University School of Medicine, Stanford, California, USA

Key Words. Autoimmune disease • Nitric oxide • Neural stem cell • Neural differentiation • Glial differentiation

Correspondence: Lou Brundin, M.D., Ph.D., Department of Clinical Neuroscience, Division of Neurology, Karolinska Institutet, 171 76 Stockholm, Sweden. Telephone: +46-8-51775412; Fax: +46-8-51773757; e-mail: Lou.Brundin{at}karolinska.se

Received December 20, 2005; accepted for publication August 8, 2006.
First published online in STEM CELLS EXPRESS   August 17, 2006.



Regeneration of cells in the central nervous system is a process that might be affected during neurological disease and trauma. Because nitric oxide (NO) and its derivatives are powerful mediators in the inflammatory cascade, we have investigated the effects of pathophysiological concentrations of NO on neurogenesis, gliogenesis, and the expression of proneural genes in primary adult neural stem cell cultures. After exposure to NO, neurogenesis was downregulated, and this corresponded to decreased expression of the proneural gene neurogenin-2 and ß-III-tubulin. The decreased ability to generate neurons was also found to be transmitted to the progeny of the cells. NO exposure was instead beneficial for astroglial differentiation, which was confirmed by increased activation of the Janus tyrosine kinase/signal transducer and activator of transcription transduction pathway. Our findings reveal a new role for NO during neuroinflammatory conditions, whereby its proastroglial fate-determining effect on neural stem cells might directly influence the neuroregenerative process.