Epigenetische Histonmodifikationen in einem Tiermodell für Depression: Chromatin-Remodelling nach frühen Stresserfahrungen

The general aim of this project is to unravel the epigenetic and molecular mechanisms underlying perinatal stress-induced dendritic and synaptic maturational changes in prefrontal and limbic brain regions, which are assumed to represent the neuronal substrate for stress-induced behavioral dysfunctions, including anxiety and depression. We will test the hypothesis that prenatal stress exposure induces chromatin remodeling, including changes in histone acetylation, which are assumed to play a key role in both the etiology and treatment of depression. We will focus on epigenetic modifications, which particularly affect gene expression and the synthesis of synaptic and cytoskeletal proteins, which are likely candidates to mediate the stress-induced dendritic and synaptic changes in the prefrontal cortex, hippocampus and the amygdala. Because many of the mental disorders associated with prenatal stress exhibit a sex bias, the molecular analysis of how sex-specific susceptibility arises will improve our mechanistic insight and lead to the identification of novel targets for protective and therapeutic development. Thus, another aim will be the identification sex-specific differences in chromatin remodeling in response to prenatal stress, which we assume to underlie the previously observed stress-induced sex-specific behavioral, molecular, dendritic and synaptic changes.