Serotonin depletion hampers survival and proliferation in neurospheres derived from adult neural stem cells

Neuropsychopharmacology. 2010 Mar;35(4):893-903. doi: 10.1038/npp.2009.181. Epub 2009 Dec 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / drug effects
  • Adult Stem Cells / physiology*
  • Analysis of Variance
  • Animals
  • 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 / pharmacology
  • Fibroblast Growth Factor 2 / pharmacology
  • Gene Expression Regulation, Enzymologic / drug effects
  • Hydroxyindoleacetic Acid / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neurons / drug effects
  • Neurons / metabolism*
  • Serotonin / deficiency*
  • Serotonin / pharmacology
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Tryptophan Hydroxylase / metabolism


  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Fibroblast Growth Factor 2
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Epidermal Growth Factor
  • Tryptophan Hydroxylase