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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Acknowledgements
We thank Tatiana Veneroso and Alberto Visioli for their excellent technical support. We express our gratitude to Donald Kuhn, Wayne State University, and to Dennis Murphy, NIMH, NIH, for providing essential antisera and chemical compounds for our experiments. We are particularly indebted to Roberta Palumbo for teaching how to do Boyden chamber experiments. A final thanks to Kent Hufford for his critical reading of the paper.
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This work is dedicated to Helmut Beckmann, the former chair of the Department of Psychiatry at the University of Wuerzburg
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This work was supported by Deutsche Forschungsgemeinschaft (DFG) Be2530 to JB, Förderprogramm Forschung und Lehre (FöFoLe) of University of Munich to JB, and SFB 531 to JB/KPL. None of the authors declare any conflict of interest.
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Benninghoff, J., Gritti, A., Rizzi, M. et al. Serotonin Depletion Hampers Survival and Proliferation in Neurospheres Derived from Adult Neural Stem Cells. Neuropsychopharmacol 35, 893–903 (2010). https://doi.org/10.1038/npp.2009.181
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DOI: https://doi.org/10.1038/npp.2009.181
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