Brain mineralocorticoid receptors as resilience factor under adverse life conditions?

Abstract

Studies in human cohorts have underlined the importance of gene-environment interactions for brain structure and function during development and in adulthood. Such interactions can make the difference between staying healthy or succumbing to disease, e.g. depression or posttraumatic stress disorder. The aim of this thesis was to investigate whether overexpression of one particular gene, i.e. the gene encoding one of two receptors for stress hormones (the mineralocorticoid receptor (MR)) in the forebrain of mice (MR-tg mice), protects against behavioral and structural changes after chronic stress, experienced early in life or in adulthood. In male mice, we found that MR overexpression indeed protects against deficiencies in context-dependent learning and adult neurogenesis (birth of neurons), but not in fear memory, seen after three weeks of chronic unpredictable stress in adulthood or after experiencing stress early in life (ELS). By contrast, in female mice MR overexpression did not affect anxiety and context-dependent learning and memory in adulthood, after experiencing ELS. Overall, in male mice we found partial support for our hypothesis that MR overexpression protects against the development of chronic stress-induced structural and/or behavioral deficits. On the one hand this potentially opens the possibility to identify individuals resilient for developing psychopathology under adverse life conditions and on the other hand –by understanding the underlying brain processes- this may help to develop new tools, e.g. pharmacological or by changing lifestyle, to treat or prevent stress-related diseases.