Effects and mechanisms of prenatal programming
The relationship between prenatal programming and ageing is undoubtedly complex involving several factors, pathways and mechanisms which appear to be critical for early brain ageing. We concentrate on linking early developmental processes with longevity and ageing with a special focus on genes and pathways. In an integrated and translational approach, this project addresses the key question “How sensitive is the stress axis to major environmental stimuli during pregnancy and how persistent are the changes throughout the entire life-span including ageing?” The project analyzes to what extent glucocorticoid receptor resistance, increased sympathetic activity, or increased cerebrovascular tone are key mediators connecting developmental modifications to early brain ageing and increased susceptibility to age-associated brain disorders in experimental studies. We will show to what extent prenatal stress programs early cognitive decline together with incidence and outcome of stroke in aged subjects. We compare the impact of different types of prenatal stress: maternal psychophysiological stress, undernutrition, and therapeutic exposure to stress hormones (glucocorticoids). The results achieved in the project will reveal to what extent the different types of prenatal stress program early brain ageing.
We have access to some of the best characterized human cohorts at different ages from early childhood to the elderly that have been exposed to prenatal stress to examine and compare the effects of major prenatal environmental factors (maternal stress, GC exposure and nutrient restriction) on structural and functional brain development and ageing, and on the predisposition for brain-related diseases (early cognitive decline and stroke).
The corresponding use of non-human primate cohorts and rodents and transgenic mice offers a truly unique opportunity to translate experimental results to humans.