NeuroNetwork 2

Environmental influences such as early-life stress (ELS) program the developing organism and influence the development of brain and behavior. Depending on the type of stressor and the duration and timing of stress-exposure this can be a critical factor for the development of behavioral dysfunctions and mental disorders but also for a positive adaptation regarding stress coping later in life. The close interaction of environmental signals with genetically preprogrammed developmental processes is mediated by epigenetic mechanisms that govern changes in transcriptional activity. Epigenetic mechanisms are characterised as alterations in genomic expression that occur independent of changes in the DNA-sequence and include DNA methylation and histone modifactions (chromatin remodelling).

In our network we focused on transient (dynamic) and long-term stable epigenetic alterations in animal models of ELS (repeated maternal separation from postnatal day 14-16). We were able to show for the first time that ELS induces a rapid increase in the expression of specific synaptic plasticity genes in the hippocampus, that are directly regulated by an increased acetylation of histone H4 as a consequence of elevated stress-hormone levels (Xie et al., 2013). Also, we revealed that ELS has long-term effects on the expression of estrogen receptors (ERβ) that influence synaptic plasticity (emotion-induced late-LTP) in the hippocampus and are regulated by changes in DNA-methylation at the promoter regions of this gene (Wang et al., 2013). Overall, the described epigenetic changes are assumed to represent a multistep process in the adaption of neuronal networks to a stressful environment.