TY - JOUR
T1 - Serotonin depletion hampers survival and proliferation in neurospheres derived from adult neural stem cells
AU - Benninghoff, Jens
AU - Gritti, Angela
AU - Rizzi, Matteo
AU - Lamorte, Giuseppe
AU - Schloesser, Robert J.
AU - Schmitt, Angelika
AU - Robel, Stefanie
AU - Genius, Just
AU - Moessner, Rainald
AU - Riederer, Peter
AU - Manji, Husseini K.
AU - Grunze, Heinz
AU - Rujescu, Dan
AU - Moeller, Hans Juergen
AU - Lesch, Klaus Peter
AU - Vescovi, Angelo Luigi
PY - 2010/3
Y1 - 2010/3
N2 - 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.
AB - 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.
KW - Brain
KW - Hippocampus
KW - Neural progenitors
KW - Neurogenesis
KW - Serotonin
KW - TPH
UR - http://www.scopus.com/inward/record.url?scp=76749112910&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=76749112910&partnerID=8YFLogxK
U2 - 10.1038/npp.2009.181
DO - 10.1038/npp.2009.181
M3 - Article
C2 - 20010549
AN - SCOPUS:76749112910
SN - 0893-133X
VL - 35
SP - 893
EP - 903
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 4
ER -