Epigenetische Programmierung von frühkindlichem Stress auf die Stressreaktion im Erwachsenenalter: die Rolle von NPY-Rezeptoren als Mediator von psychischer Gesundheit und Krankheit

Early life adversity and early life stress (ELS) constitute major risk factors that contribute to the aetiology of various psychiatric disorders which emerge during puberty and adulthood. The vast majority of animal studies on ELA have studied the impact of a single brief or chronic stress episode during defined developmental time windows. However, in "normal” life individuals "collect” many experiences of stress, trauma and neglect throughout life. Using an animal model of consecutive stress exposure (neonatal, periadolescent, adult) in mice we address the following questions: Do consecutive stressors during critical developmental phases accumulate and potentiate their effects and thereby increase the risk for the development of mental disorders? Or can consecutive ELS episodes induce adaptive neuronal and behavioral changes making an individual resilient towards an adverse environment later in life? We hypothesize that ELS can programm the expression of NPY-receptors in limbic and prefrontal brain areas via epigenetic mechanisms and thereby influencing stress response at later life periods. Thus, we will assess epigenetic changes (DNA-methylation, histone-modifications) at the promoter regions of NPY-receptors that may influence gene expression changes in response to single or consecutive stress exposure. Another focus of this project will be on potential sex-specific differences in susceptibility and resilience.