Project Details
Projekt
Inter- and transgenerational consequences of early life adversity on oxytocin-receptor gene expression
Subject Area
Biological Psychiatry
Term
since 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 444836698
Exposure to one or multiple forms of early-life adversity (ELA) constitutes a major risk factor for developing somatic and behavioral disorders and in the etiology of a wide range of mental disorders. Evidence is emerging that behavioral and brain structural/functional consequences of ELA can be transmitted to the next generations, however, the detailed mechanisms underlying inter- and transgenerational transmission of ELA are still poorly understood. In our animal model for ELA we will attempt to unveil causal relationships between ELA exposure, behavioral dysfunctions, changes in oxytocin receptor (OxtR) gene expression and underlying epigenetic modifications in brain and oocytes. Based on our previous findings the aim of this project is to assess i) whether changes of OxtR gene expression, which we observed in ELA exposed F0 mothers are transmitted to the next (F1, F2) generations, and ii) if these changes are epigenetically regulated via DNA-methylation and/or histone modofications. Considering transgenerational epigenetic inheritance via the maternal line in mammals and in particular human populations, we will also identify ELA transmission paths, i.e. if transmission is mediated via behavioral maternal traits and/or through epigenetic changes in oocytes.Since most of what is known about the effects of ELA on brain development arises from experimental studies in male individuals, which is somewhat surprising in view of the considerable sex-bias in the prevalence of ELA-induced disorders, another aim of this project is to deepen our knowledge about sex-specific effects of ELA and to characterize sex as vulnerability or resiliency factor.
DFG Programme
Research Grants
