TY  - JOUR
A1  - Van den Hove, Daniel
A1  - Jakob, Sissi Brigitte
A1  - Schraut, Karla-Gerlinde
A1  - Kenis, Gunter
A1  - Schmitt, Angelika Gertrud
A1  - Kneitz, Susanne
A1  - Scholz, Claus-Jürgen
A1  - Wiescholleck, Valentina
A1  - Ortega, Gabriela
A1  - Prickaerts, Jos
A1  - Steinbusch, Harry
A1  - Lesch, Klaus-Peter
T1  - Differential Effects of Prenatal Stress in 5-Htt Deficient Mice: Towards Molecular Mechanisms of Gene x Environment Interactions
JF  - PLoS ONE
N2  - 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.
KW  - Serotonin transporter polymorphism
KW  - Acute tryptophan depletion
KW  - Anxiety-like behavior
KW  - Long-term depression
KW  - Knock-out mice
KW  - Major depression
KW  - Interferon-alpha
KW  - Physiological functions
KW  - Restraint stress
KW  - Bipolar disorder
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135111
VL  - 6
IS  - 8
ER  -