Nitric oxide exposure diverts neural stem cell fate from neurogenesis towards astrogliogenesis.
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 beta-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.
Covacu
Ruxandra
R
Department of Clinical Neuroscience, Division of Neurology, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden.
Danilov
Alexandre I
AI
Rasmussen
Bo Sonnich
BS
Hallén
Katarina
K
Moe
Morten C
MC
Lobell
Anna
A
Johansson
Clas B
CB
Svensson
Mikael A
MA
Olsson
Tomas
T
Brundin
Lou
L
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage / Q000187:drug effects*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects
D005904:Glial Fibrillary Acidic Protein; D009603:Nitroso Compounds; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D009569:Nitric Oxide; D010100:Oxygen