Genes, Hormones and the Brain: Modeling Clinically Relevant Endophenotypes of Major Depression in Mice Selected for Extremes in Stress Reactivity

Abstract

Event Abstract Back to Event Genes, Hormones and the Brain: Modeling Clinically Relevant Endophenotypes of Major Depression in Mice Selected for Extremes in Stress Reactivity Chadi Touma1*, Rupert Palme2, Florian Holsboer1 and Rainer Landgraf1 1 Max Planck Institute of Psychiatry, Germany 2 University of Veterinary Medicine, Austria Affective disorders are among the most prevalent and costly diseases of the central nervous system. In recent years, it has become evident that alterations of the stress hormone system, in particular dysfunctions of the HPA axis, play a prominent role in the aetiology of major depression. Therefore, we aimed to generate a new animal model comprising these neuroendocrine core symptoms in order to unravel the mechanisms underlying increased or decreased stress reactivity. Starting from a population of outbred mice, two breeding lines were established according to the outcome of a “stress reactivity test” (SRT), consisting of a 15-min restraint period and tail blood samplings immediately before and after the stressor. Mice showing a high or a low secretion of corticosterone in the SRT were selected for the “high reactivity” (HR) and the “low reactivity” (LR) breeding line, respectively. Additionally, a third breeding line with an “intermediate reactivity” (IR) in the SRT was established. Already in the first generation, significant differences in HPA axis reactivity between HR, IR, and LR mice were observed. These differences remained stable across all subsequent generations and could be increased by selective inbreeding. Repeated testing in the SRT furthermore proved that the observed differences in stress responsiveness are already present early in life and can be regarded as a robust genetic predisposition. Emotional behaviour testing, sleep EEG measurements and morphometric, neuroendocrine, and gene expression findings also point to similarities with depressive patients. Taken together, our results indicate that distinct mechanisms influencing the function and regulation of the HPA axis seem to mediate the respective behavioural and neurobiological endophenotypes. Thus, the generated HR/IR/LR mouse lines are a valuable model to elucidate the molecular-genetic underpinnings of altered stress reactivity and thereby improve our understanding of affective disorders. Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Touma C, Palme R, Holsboer F and Landgraf R (2009). Genes, Hormones and the Brain: Modeling Clinically Relevant Endophenotypes of Major Depression in Mice Selected for Extremes in Stress Reactivity. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.323 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 15 Jun 2009; Published Online: 15 Jun 2009. * Correspondence: Chadi Touma, Max Planck Institute of Psychiatry, Munich, Germany, chadi.touma@uni-osnabrueck.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Chadi Touma Rupert Palme Florian Holsboer Rainer Landgraf Google Chadi Touma Rupert Palme Florian Holsboer Rainer Landgraf Google Scholar Chadi Touma Rupert Palme Florian Holsboer Rainer Landgraf PubMed Chadi Touma Rupert Palme Florian Holsboer Rainer Landgraf Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.