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Differential Effects of Prenatal Stress in 5-Htt Deficient Mice: Towards Molecular Mechanisms of Gene × Environment Interactions

Prenatal stress (PS) has been shown to influence the development of the fetal brain and to increase the risk for the development of psychiatric disorders in later life. Furthermore, the variation of human serotonin transporter (5-HTT, SLC6A4) gene was suggested to exert a modulating effect on the as...

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Autores principales: Van den Hove, Daniel, Jakob, Sissi Brigitte, Schraut, Karla-Gerlinde, Kenis, Gunter, Schmitt, Angelika Gertrud, Kneitz, Susanne, Scholz, Claus-Jürgen, Wiescholleck, Valentina, Ortega, Gabriela, Prickaerts, Jos, Steinbusch, Harry, Lesch, Klaus-Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155516/
https://www.ncbi.nlm.nih.gov/pubmed/21857948
http://dx.doi.org/10.1371/journal.pone.0022715
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author Van den Hove, Daniel
Jakob, Sissi Brigitte
Schraut, Karla-Gerlinde
Kenis, Gunter
Schmitt, Angelika Gertrud
Kneitz, Susanne
Scholz, Claus-Jürgen
Wiescholleck, Valentina
Ortega, Gabriela
Prickaerts, Jos
Steinbusch, Harry
Lesch, Klaus-Peter
author_facet Van den Hove, Daniel
Jakob, Sissi Brigitte
Schraut, Karla-Gerlinde
Kenis, Gunter
Schmitt, Angelika Gertrud
Kneitz, Susanne
Scholz, Claus-Jürgen
Wiescholleck, Valentina
Ortega, Gabriela
Prickaerts, Jos
Steinbusch, Harry
Lesch, Klaus-Peter
author_sort Van den Hove, Daniel
collection PubMed
description Prenatal stress (PS) has been shown to influence the development of the fetal brain and to increase the risk for the development of psychiatric disorders in later life. Furthermore, the variation of human serotonin transporter (5-HTT, SLC6A4) gene was suggested to exert a modulating effect on the association between early life stress and the risk for depression. In the present study, we used a 5-Htt×PS paradigm to investigate whether the effects of PS are dependent on the 5-Htt genotype. For this purpose, the effects of PS on cognition, anxiety- and depression-related behavior were examined using a maternal restraint stress paradigm of PS in C57BL6 wild-type (WT) and heterozygous 5-Htt deficient (5-Htt +/−) mice. Additionally, in female offspring, a genome-wide hippocampal gene expression profiling was performed using the Affymetrix GeneChip® Mouse Genome 430 2.0 Array. 5-Htt +/− offspring showed enhanced memory performance and signs of reduced anxiety as compared to WT offspring. In contrast, exposure of 5-Htt +/− mice to PS was associated with increased depressive-like behavior, an effect that tended to be more pronounced in female offspring. Further, 5-Htt genotype, PS and their interaction differentially affected the expression of numerous genes and related pathways within the female hippocampus. Specifically, MAPK and neurotrophin signaling were regulated by both the 5-Htt +/− genotype and PS exposure, whereas cytokine and Wnt signaling were affected in a 5-Htt genotype×PS manner, indicating a gene×environment interaction at the molecular level. In conclusion, our data suggest that although the 5-Htt +/− genotype shows clear adaptive capacity, 5-Htt +/− mice –particularly females– at the same time appear to be more vulnerable to developmental stress exposure when compared to WT offspring. Moreover, hippocampal gene expression profiles suggest that distinct molecular mechanisms mediate the behavioral effects of the 5-Htt genotype, PS exposure, and their interaction.
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spelling pubmed-31555162011-08-19 Differential Effects of Prenatal Stress in 5-Htt Deficient Mice: Towards Molecular Mechanisms of Gene × Environment Interactions Van den Hove, Daniel Jakob, Sissi Brigitte Schraut, Karla-Gerlinde Kenis, Gunter Schmitt, Angelika Gertrud Kneitz, Susanne Scholz, Claus-Jürgen Wiescholleck, Valentina Ortega, Gabriela Prickaerts, Jos Steinbusch, Harry Lesch, Klaus-Peter PLoS One Research Article Prenatal stress (PS) has been shown to influence the development of the fetal brain and to increase the risk for the development of psychiatric disorders in later life. Furthermore, the variation of human serotonin transporter (5-HTT, SLC6A4) gene was suggested to exert a modulating effect on the association between early life stress and the risk for depression. In the present study, we used a 5-Htt×PS paradigm to investigate whether the effects of PS are dependent on the 5-Htt genotype. For this purpose, the effects of PS on cognition, anxiety- and depression-related behavior were examined using a maternal restraint stress paradigm of PS in C57BL6 wild-type (WT) and heterozygous 5-Htt deficient (5-Htt +/−) mice. Additionally, in female offspring, a genome-wide hippocampal gene expression profiling was performed using the Affymetrix GeneChip® Mouse Genome 430 2.0 Array. 5-Htt +/− offspring showed enhanced memory performance and signs of reduced anxiety as compared to WT offspring. In contrast, exposure of 5-Htt +/− mice to PS was associated with increased depressive-like behavior, an effect that tended to be more pronounced in female offspring. Further, 5-Htt genotype, PS and their interaction differentially affected the expression of numerous genes and related pathways within the female hippocampus. Specifically, MAPK and neurotrophin signaling were regulated by both the 5-Htt +/− genotype and PS exposure, whereas cytokine and Wnt signaling were affected in a 5-Htt genotype×PS manner, indicating a gene×environment interaction at the molecular level. In conclusion, our data suggest that although the 5-Htt +/− genotype shows clear adaptive capacity, 5-Htt +/− mice –particularly females– at the same time appear to be more vulnerable to developmental stress exposure when compared to WT offspring. Moreover, hippocampal gene expression profiles suggest that distinct molecular mechanisms mediate the behavioral effects of the 5-Htt genotype, PS exposure, and their interaction. Public Library of Science 2011-08-12 /pmc/articles/PMC3155516/ /pubmed/21857948 http://dx.doi.org/10.1371/journal.pone.0022715 Text en Van den Hove et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Van den Hove, Daniel
Jakob, Sissi Brigitte
Schraut, Karla-Gerlinde
Kenis, Gunter
Schmitt, Angelika Gertrud
Kneitz, Susanne
Scholz, Claus-Jürgen
Wiescholleck, Valentina
Ortega, Gabriela
Prickaerts, Jos
Steinbusch, Harry
Lesch, Klaus-Peter
Differential Effects of Prenatal Stress in 5-Htt Deficient Mice: Towards Molecular Mechanisms of Gene × Environment Interactions
title Differential Effects of Prenatal Stress in 5-Htt Deficient Mice: Towards Molecular Mechanisms of Gene × Environment Interactions
title_full Differential Effects of Prenatal Stress in 5-Htt Deficient Mice: Towards Molecular Mechanisms of Gene × Environment Interactions
title_fullStr Differential Effects of Prenatal Stress in 5-Htt Deficient Mice: Towards Molecular Mechanisms of Gene × Environment Interactions
title_full_unstemmed Differential Effects of Prenatal Stress in 5-Htt Deficient Mice: Towards Molecular Mechanisms of Gene × Environment Interactions
title_short Differential Effects of Prenatal Stress in 5-Htt Deficient Mice: Towards Molecular Mechanisms of Gene × Environment Interactions
title_sort differential effects of prenatal stress in 5-htt deficient mice: towards molecular mechanisms of gene × environment interactions
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155516/
https://www.ncbi.nlm.nih.gov/pubmed/21857948
http://dx.doi.org/10.1371/journal.pone.0022715
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