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

Abstract 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...

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Autores principales:	B. Aboagye, T. Weber, H. L. Merdian, D. Bartsch, K. P. Lesch, J. Waider
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dec780cc9c21464bb2794b7d93a46140
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spelling	oai:doaj.org-article:dec780cc9c21464bb2794b7d93a461402021-12-02T13:20:20ZSerotonin deficiency induced after brain maturation rescues consequences of early life adversity10.1038/s41598-021-83592-42045-2322https://doaj.org/article/dec780cc9c21464bb2794b7d93a461402021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83592-4https://doaj.org/toc/2045-2322Abstract 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. The impact of Tph2 icKO in interaction with MS stress (Tph2 icKO × MS) 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.B. AboagyeT. WeberH. L. MerdianD. BartschK. P. LeschJ. WaiderNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q B. Aboagye T. Weber H. L. Merdian D. Bartsch K. P. Lesch J. Waider Serotonin deficiency induced after brain maturation rescues consequences of early life adversity
description	Abstract 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. The impact of Tph2 icKO in interaction with MS stress (Tph2 icKO × MS) 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.
format	article
author	B. Aboagye T. Weber H. L. Merdian D. Bartsch K. P. Lesch J. Waider
author_facet	B. Aboagye T. Weber H. L. Merdian D. Bartsch K. P. Lesch J. Waider
author_sort	B. Aboagye
title	Serotonin deficiency induced after brain maturation rescues consequences of early life adversity
title_short	Serotonin deficiency induced after brain maturation rescues consequences of early life adversity
title_full	Serotonin deficiency induced after brain maturation rescues consequences of early life adversity
title_fullStr	Serotonin deficiency induced after brain maturation rescues consequences of early life adversity
title_full_unstemmed	Serotonin deficiency induced after brain maturation rescues consequences of early life adversity
title_sort	serotonin deficiency induced after brain maturation rescues consequences of early life adversity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/dec780cc9c21464bb2794b7d93a46140
work_keys_str_mv	AT baboagye serotonindeficiencyinducedafterbrainmaturationrescuesconsequencesofearlylifeadversity AT tweber serotonindeficiencyinducedafterbrainmaturationrescuesconsequencesofearlylifeadversity AT hlmerdian serotonindeficiencyinducedafterbrainmaturationrescuesconsequencesofearlylifeadversity AT dbartsch serotonindeficiencyinducedafterbrainmaturationrescuesconsequencesofearlylifeadversity AT kplesch serotonindeficiencyinducedafterbrainmaturationrescuesconsequencesofearlylifeadversity AT jwaider serotonindeficiencyinducedafterbrainmaturationrescuesconsequencesofearlylifeadversity
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Serotonin deficiency induced after brain maturation rescues consequences of early life adversity

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