Serotonin deficiency induced after brain maturation rescues consequences of early life adversity

Please always quote using this 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.show moreshow less

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Metadaten
Author: B. Aboagye, T. Weber, H. L. Merdian, D. Bartsch, K. P. Lesch, J. Waider
URN:urn:nbn:de:bvb:20-opus-258626
Document Type:Journal article
Faculties:Medizinische Fakultät / Lehrstuhl für Molekulare Psychiatrie
Language:English
Parent Title (English):Scientific Reports
ISSN:2045-2322
Year of Completion:2021
Volume:11
Issue:1
Article Number:5368
Source: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
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:emotion; molecular medicine; neuroscience
Release Date:2022/03/18
EU-Project number / Contract (GA) number:602805
EU-Project number / Contract (GA) number:728018
OpenAIRE:OpenAIRE
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2021
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International