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

doi:10.1038/npp.2009.181

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

Academic Institute

Research output: Contribution to journal › Article › peer-review

41 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 language	English (US)
Pages (from-to)	893-903
Number of pages	11
Journal	Neuropsychopharmacology
Volume	35
Issue number	4
DOIs	https://doi.org/10.1038/npp.2009.181
State	Published - Mar 2010

Keywords

Brain
Hippocampus
Neural progenitors
Neurogenesis
Serotonin
TPH

ASJC Scopus subject areas

Pharmacology
Psychiatry and Mental health

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10.1038/npp.2009.181

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Benninghoff, J., Gritti, A., Rizzi, M., Lamorte, G., Schloesser, R. J., Schmitt, A., Robel, S., Genius, J., Moessner, R., Riederer, P., Manji, H. K., Grunze, H., Rujescu, D., Moeller, H. J., Lesch, K. P., & Vescovi, A. L. (2010). Serotonin depletion hampers survival and proliferation in neurospheres derived from adult neural stem cells. Neuropsychopharmacology, 35(4), 893-903. https://doi.org/10.1038/npp.2009.181

Benninghoff, J, Gritti, A, Rizzi, M, Lamorte, G, Schloesser, RJ, Schmitt, A, Robel, S, Genius, J, Moessner, R, Riederer, P, Manji, HK, Grunze, H, Rujescu, D, Moeller, HJ, Lesch, KP & Vescovi, AL 2010, 'Serotonin depletion hampers survival and proliferation in neurospheres derived from adult neural stem cells', Neuropsychopharmacology, vol. 35, no. 4, pp. 893-903. https://doi.org/10.1038/npp.2009.181

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title = "Serotonin depletion hampers survival and proliferation in neurospheres derived from adult neural stem cells",

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.",

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

note = "Funding Information: This work was supported by Deutsche Forschungsge-meinschaft (DFG) Be2530 to JB, F{\"o}rderprogramm For-schung und Lehre (F{\"o}FoLe) of University of Munich to JB, and SFB 531 to JB/KPL. None of the authors declare any conflict of interest. Copyright: Copyright 2011 Elsevier B.V., All rights reserved.",

year = "2010",

month = mar,

doi = "10.1038/npp.2009.181",

language = "English (US)",

volume = "35",

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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

N1 - Funding Information: This work was supported by Deutsche Forschungsge-meinschaft (DFG) Be2530 to JB, Förderprogramm For-schung und Lehre (FöFoLe) of University of Munich to JB, and SFB 531 to JB/KPL. None of the authors declare any conflict of interest. Copyright: Copyright 2011 Elsevier B.V., All rights reserved.

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.

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KW - Hippocampus

KW - Neural progenitors

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KW - Serotonin

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JF - Neuropsychopharmacology

IS - 4

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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