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- Title
Serotonin Depletion Hampers Survival and Proliferation in Neurospheres Derived from Adult Neural Stem Cells.
- 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
- Abstract
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.
- Subjects
SEROTONIN; DEVELOPMENTAL neurobiology; STEM cells; ENZYME inhibitors; CYTOKINES
- Publication
Neuropsychopharmacology, 2010, Vol 35, Issue 4, p893
- ISSN
0893-133X
- Publication type
Article
- DOI
10.1038/npp.2009.181