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Mineralocorticoid- and glucocorticoid receptor systems and emotional memory: a human genetics approach. (EMRC/ECORES/07-EUROSTRESS-FP-005)

English title Mineralocorticoid- and glucocorticoid receptor systems and emotional memory: a human genetics approach. (EMRC/ECORES/07-EUROSTRESS-FP-005)
Applicant De Quervain Dominique
Number 124236
Funding scheme Project funding (special)
Research institution Abteilung für Psychiatrische Forschung Psychiatrische Universitätsklinik Zürich
Institution of higher education University of Zurich - ZH
Main discipline Neurophysiology and Brain Research
Start/End 01.09.2008 - 31.08.2011
Approved amount 483'469.00
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All Disciplines (4)

Discipline
Neurophysiology and Brain Research
Neurology, Psychiatry
Genetics
Biochemistry

Keywords (10)

stress; glucocorticoids; glucocorticoid receptor; mineralcorticoid receptor; memory; genetics; emotion; health; polymorhism; posttraumatic stress disorder

Lay Summary (English)

Lead
Lay summary
A fundamental question in stress research is why some individuals become vulnerable to affective disease, while others are resilient and gain strength from stressful experiences. In this multidisciplinary program we focus in a translational approach on the role of glucocorticoids, stress hormones released from the adrenal cortex. Secreted glucocorticoids target the brain, where their actions on emotional arousal, cognition and motivation are mediated by mineralocorticoid and glucocorticoid receptors (MR and GR). Recent evidence from our laboratories suggests that these receptors operate in concert with the other stress mediators, in all phases of the stress response from the onset to the recovery and from appraisal to memory storage/retrieval processes and affective responses. We test the hypothesis that imbalance in MR:GR mediated processes threatens affective health. Our objective is to understand how glucocorticoids, which are essential for adaptation and mental health, can become harmful. We have the following specific aims:1) to generate animal models with altered MR:GR balance via transgenic and lentiviral approaches (Prof. R. de Kloet, Netherlands) 2) to induce enduring MR:GR changes in response to maternal care and perinatal challenges (Prof. J. Seckl, UK)3) to examine the behavioral and neuroendocrine phenotype of these MR:GR modulated models (Prof. R. de Kloet, Prof. J. Seckl)4) to relate genetic variation in human MRs and GRs to emotional and traumatic memories as well as vulnerability to and symptoms of posttraumatic stress disorder (Prof. D. de Quervain, Prof. A. Papassotiropoulos, Switzerland)5) to study hypothalamic-pituitary-adrenal axis activity in Alzheimer’s Disease and chronic burnout patients and to relate genetic variation in human MRs and GRs to cognition and affective health (Prof. T. Olsson, Sweden)Relevance of the projectWith this international research initiative we intend to gain novel insights in the role of the mineralocorticoid- and glucocorticoid system in physiological and pathophysiological processes of emotion and memory.
Direct link to Lay Summary Last update: 21.02.2013

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