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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-135111
  • 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-HttxPS paradigm to investigate whether the effects of PS are dependent on the 5-Htt genotype. For this purpose, the effects of PS on cognition,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-HttxPS 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 (R) 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 genotypexPS manner, indicating a genexenvironment 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.show moreshow less

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Metadaten
Author: Daniel Van den Hove, Sissi Brigitte Jakob, Karla-Gerlinde Schraut, Gunter Kenis, Angelika Gertrud Schmitt, Susanne Kneitz, Claus-Jürgen Scholz, Valentina Wiescholleck, Gabriela Ortega, Jos Prickaerts, Harry Steinbusch, Klaus-Peter Lesch
URN:urn:nbn:de:bvb:20-opus-135111
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Language:English
Parent Title (English):PLoS ONE
Year of Completion:2011
Volume:6
Issue:8
Pagenumber:e22715
Source:PLoS ONE 6(8): e22715. doi:10.1371/journal.pone.0022715
DOI:https://doi.org/10.1371/journal.pone.0022715
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Acute tryptophan depletion; Anxiety-like behavior; Bipolar disorder; Interferon-alpha; Knock-out mice; Long-term depression; Major depression; Physiological functions; Restraint stress; Serotonin transporter polymorphism
Release Date:2019/03/26
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung