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

Jens Benninghoff, Angela Gritti, Matteo Rizzi, Giuseppe Lamorte, Robert J. Schloesser, Angelika Schmitt, Stefanie Robel, Just Genius, Rainald Moessner, Peter Riederer, Husseini K. Manji, Heinz Grunze, Dan Rujescu, Hans Juergen Moeller, Klaus Peter Lesch, Angelo Luigi Vescovi

Research output: Contribution to journalArticle

33 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)893-903
Number of pages11
JournalNeuropsychopharmacology
Volume35
Issue number4
DOIs
StatePublished - Mar 2010

Keywords

  • Brain
  • Hippocampus
  • Neural progenitors
  • Neurogenesis
  • Serotonin
  • TPH

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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