Submitted on December 20, 2005
Accepted on August 8, 2006
Tissue-Specific Stem Cells
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Nitric Oxide Exposure Diverts Neural Stem Cell Fate from Neurogenesis towards Astrogliogenesis
Ruxandra Covacu 1,
Alexandre I. Danilov 1,
Bo Sonnich Rasmussen 1,
Katarina Hallén 2,
Morten C. Moe 3,
Anna Lobell 1,
Clas B. Johansson 4,
Mikael A. Svensson 3,
Tomas Olsson 1,
Lou Brundin 1*
1 Department of Clinical Neuroscience, Division of Neuroimmunology, Karolinska Institutet, Stockholm, Sweden
2 Department of Molecular Medicine and Surgery, Division of Urology, Karolinska Institutet, Stockholm, Sweden
3 Department of Neurosurgery, Karolinska Institutet, Stockhom, Sweden
4 Baxter Laboratory in Genetic Pharmacology, Stanford, California
* To whom correspondence should be addressed. E-mail: Lou.Brundin{at}karolinska.se.
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Abstract |
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Regeneration of cells in the central nervous system (CNS) is a process that might be affected during neurological disease and trauma. Since 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 pro-neural genes in primary adult neural stem cell cultures. After exposure to NO, neurogenesis was downregulated and this corresponded to decreased expression of the pro-neural gene neurogenin-2, and 
-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 JAK/STAT-1 signal transduction pathway. Our findings reveal a new role for NO during neuroinflammatory conditions whereby its pro-astroglial fatedetermining effect on neural stem cells might directly influence the neuroregenerative process.
