title: Differential effects of prenatal stress in female 5-HTT-deficient mice: towards molecular mechanisms of resilience.
abstract: Prenatal stress (PS) exposure is known to increase the risk of developing emotional disorders like major depression in later life. However, some individuals do not succumb to adversity following developmental stress exposure, a phenomenon referred to as resilience. To date, the molecular mechanisms explaining why some subjects are vulnerable and others more resilient to PS are far from understood. Recently, we have shown that the serotonin transporter (5-HTT) gene may play a modulating role in rendering individuals susceptible or resilient to PS. However, it is not clear which molecular players are mediating the interaction between PS and the 5-Htt genotype in the context of vulnerability and resilience to PS. For this purpose, we performed a microarray study with the help of Affymetrix GeneChip® Mouse Genome 430 2.0 Array, in which we separated wild-type and heterozygous 5-Htt-deficient (5-Htt+/-) PS offspring into susceptible and resilient offspring according to their performance in the forced swim test. Performance-oriented LIMMA analysis on the mRNA expression microarray data was followed by subsequent Spearman's correlation analysis linking the individual qRT-PCR mRNA expression data to various anxiety- and depression-related behavioral and neuroendocrine measures. Results indicate that, amongst others, Fos-induced growth factor (Figf), galanin receptor 3 (Galr3), growth hormone (Gh) and prolactin (Prl) were differentially expressed specifically in resilient offspring when compared to controls, and that the hippocampal expression of these genes showed several strong correlations with various measures of the hypothalamus-pituitary-adrenal axis (re)activity. In conclusion, there seems to be an intricate interplay between the expression of Figf, Galr3, Gh and Prl and neuroendocrine regulation, which may be critical in mediating resilience to PS exposure. More insight into the exact role of these molecular players may significantly enhance the development of new treatment strategies for stress-related emotional disorders.
authors.affiliation: Department of Neuroscience, School for Mental Health and Neuroscience (MHENS), Maastricht University, Maastricht, The Netherlands.
authors.forename: Sissi
authors.initials: S
authors.lastname: Jakob
authors.forename: Karla-Gerlinde
authors.initials: KG
authors.lastname: Schraut
authors.forename: Angelika G
authors.initials: AG
authors.lastname: Schmitt
authors.forename: Claus-Jürgen
authors.initials: CJ
authors.lastname: Scholz
authors.forename: Gabriela
authors.initials: G
authors.lastname: Ortega
authors.forename: Harry W
authors.initials: HW
authors.lastname: Steinbusch
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
authors.forename: Daniel L A
authors.initials: DL
authors.lastname: van den Hove
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003348:Cortisone / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D013006:Growth Hormone / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology*; D011388:Prolactin / Q000235:genetics; D044093:Receptor, Galanin, Type 3 / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000172:deficiency* / Q000235:genetics; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism; D042643:Vascular Endothelial Growth Factor D / Q000235:genetics
chemical_list: D044093:Receptor, Galanin, Type 3; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D042643:Vascular Endothelial Growth Factor D; D011388:Prolactin; D013006:Growth Hormone; D003348:Cortisone