Serotonin depletion hampers survival and proliferation in neurospheres derived from adult neural stem cells.
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.
Benninghoff
Jens
J
S. Raffaele Scientific Institute, Stem Cell Research Institute (HSR-SCRI), Milan, Italy. jens.benninghoff@med.uni-muenchen.de
Gritti
Angela
A
Rizzi
Matteo
M
Lamorte
Giuseppe
G
Schloesser
Robert J
RJ
Schmitt
Angelika
A
Robel
Stefanie
S
Genius
Just
J
Moessner
Rainald
R
Riederer
Peter
P
Manji
Husseini K
HK
Grunze
Heinz
H
Rujescu
Dan
D
Moeller
Hans-Juergen
HJ
Lesch
Klaus-Peter
KP
Vescovi
Angelo Luigi
AL
D053687:Adult Stem Cells / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000172:deficiency* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D016222:Fibroblast Growth Factor 2; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D004815:Epidermal Growth Factor; D014365:Tryptophan Hydroxylase