Serotonin Depletion Hampers Survival and Proliferation in Neurospheres Derived from Adult Neural Stem Cells

• Published in: Neuropsychopharmacology (New York, N.Y.) N.Y.), 2010-03, Vol.35 (4), p.893-903
• Main Authors: Benninghoff, Jens, Gritti, Angela, Rizzi, Matteo, LaMorte, Giuseppe, Schloesser, Robert J, Schmitt, Angelika, Robel, Stefanie, Genius, Just, Moessner, Rainald, Riederer, Peter, Manji, Husseini K, Grunze, Heinz, Rujescu, Dan, Moeller, Hans-Juergen, Lesch, Klaus-Peter, Vescovi, Angelo Luigi
• Format: Article
• Language: English
• Subjects: Adult Stem Cells - drug effects; Adult Stem Cells - physiology; Analysis of Variance; Animals; Antidepressants; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Brain research; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Movement - drug effects; Cell Movement - physiology; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell Survival - physiology; Cells, Cultured; Chromatography, High Pressure Liquid - methods; Epidermal growth factor; Epidermal Growth Factor - pharmacology; Experiments; Fibroblast Growth Factor 2 - pharmacology; Fibroblasts; Gene Expression Regulation, Enzymologic - drug effects; Hydroxyindoleacetic Acid - metabolism; Medical research; Medical sciences; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Neurogenesis; Neurons - drug effects; Neurons - metabolism; Neurosciences; Original; original-article; Pharmacotherapy; Psychiatry; Serotonin; Serotonin - deficiency; Serotonin - pharmacology; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology; Stem cells; Tryptophan Hydroxylase - metabolism
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/npp.2009.181

Serotonin (5-HT) and the serotonergic system have recently been indicated as modulators of adult hippocampal neurogenesis. In this study, we evaluated the role of 5-HT on the functional features in neurospheres derived from adult neural stem cells (ANSC). We cultured neurospheres derived from mouse hippocampus in serum-free medium containing epidermal (EGF) and type-2 fibroblast growth factor (FGF2). Under these conditions ANSC expressed both isoforms of tryptophane-hydroxylase (TPH) and produced 5-HT. Blocking TPH function by para-chlorophenylalanine (PCPA) reduced ANSC proliferation, which was rescued by exogenous 5-HT. 5-HT action on ANSC was mediated predominantly by the serotonin receptor subtype 5-HT1A and, to a lesser extent, through the 5-HT2C (receptor) subtype, as shown by selectively antagonizing these receptors. Finally, we documented a 5-HT-induced increase of ANSC migration activity. In summary, we demonstrated a powerful serotonergic impact on ANSC functional features, which was mainly mediated by 5-HT1A receptors.