Serotonin deficiency induced after brain maturation rescues consequences of early life adversity
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-258626
- Brain serotonin (5-HT) system dysfunction is implicated in depressive disorders and acute depletion of 5-HT precursor tryptophan has frequently been used to model the influence of 5-HT deficiency on emotion regulation. Tamoxifen (TAM)-induced Cre/loxP-mediated inactivation of the tryptophan hydroxylase-2 gene (Tph2) was used to investigate the effects of provoked 5-HT deficiency in adult mice (Tph2 icKO) previously subjected to maternal separation (MS). The efficiency of Tph2 inactivation was validated by immunohistochemistry and HPLC. TheBrain serotonin (5-HT) system dysfunction is implicated in depressive disorders and acute depletion of 5-HT precursor tryptophan has frequently been used to model the influence of 5-HT deficiency on emotion regulation. Tamoxifen (TAM)-induced Cre/loxP-mediated inactivation of the tryptophan hydroxylase-2 gene (Tph2) was used to investigate the effects of provoked 5-HT deficiency in adult mice (Tph2 icKO) previously subjected to maternal separation (MS). The efficiency of Tph2 inactivation was validated by immunohistochemistry and HPLC. The impact of Tph2 icKO in interaction with MS stress (Tph2 icKOxMS) on physiological parameters, emotional behavior and expression of 5-HT system-related marker genes were assessed. Tph2 icKO mice displayed a significant reduction in 5-HT immunoreactive cells and 5-HT concentrations in the rostral raphe region within four weeks following TAM treatment. Tph2 icKO and MS differentially affected food and water intake, locomotor activity as well as panic-like escape behavior. Tph2 icKO prevented the adverse effects of MS stress and altered the expression of the genes previously linked to stress and emotionality. In conclusion, an experimental model was established to study the behavioral and neurobiological consequences of 5-HT deficiency in adulthood in interaction with early-life adversity potentially affecting brain development and the pathogenesis of depressive disorders.…
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| Autor(en): | B. Aboagye, T. Weber, H. L. Merdian, D. Bartsch, K. P. Lesch, J. Waider |
|---|---|
| URN: | urn:nbn:de:bvb:20-opus-258626 |
| Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
| Institute der Universität: | Medizinische Fakultät / Lehrstuhl für Molekulare Psychiatrie |
| Sprache der Veröffentlichung: | Englisch |
| Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Scientific Reports |
| ISSN: | 2045-2322 |
| Erscheinungsjahr: | 2021 |
| Band / Jahrgang: | 11 |
| Heft / Ausgabe: | 1 |
| Aufsatznummer: | 5368 |
| Originalveröffentlichung / Quelle: | Scientific Reports (2021) 11:1, 5368 . https://doi.org/10.1038/s41598-021-83592-4 |
| DOI: | https://doi.org/10.1038/s41598-021-83592-4 |
| Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
| Freie Schlagwort(e): | emotion; molecular medicine; neuroscience |
| Datum der Freischaltung: | 18.03.2022 |
| EU-Projektnummer / Contract (GA) number: | 602805 |
| EU-Projektnummer / Contract (GA) number: | 728018 |
| OpenAIRE: | OpenAIRE |
| Sammlungen: | Open-Access-Publikationsfonds / Förderzeitraum 2021 |
| Lizenz (Deutsch): |  CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |