Impact of Prenatal Stress on BRAIN AGEing
Coordinator: Matthias SCHWAB
Project Number: 279281
EC contribution: € 2,998,420.00
Project website: http://www.brain-age.eu/
TA healthy brain is a major determinant of good life-long health, facilitating integration into society at all ages. Human epidemiological and animal studies indicate that in addition to life style and genetic factors, environmental influences in prenatal life have a major impact on brain ageing and age-associated brain disorders.
We hypothesize that:
- prenatal stress programs early brain ageing;
- this predisposes to age-associated brain diseases including cognitive decline and stroke;
- epigenetic changes affecting glucocorticoid receptor (GR) sensitivity, altered autonomic nervous system (ANS) reactivity and cerebrovascular tone are important mediators of these processes;
- these changes represent targets for diagnosis and therapeutic interventions.
Our consortium has unique access to well defined human and non-human primate cohorts (age range 2-84 y equivalents) exposed to different types of prenatal stress. Mechanisms of prenatal programming will be tested experimentally. We employ innovative techniques to characterize brain ageing, namely MRI based volumetry, non-linear analysis of EEG and ANS, advanced molecular techniques including epigenetics and metabolomics and neuropsychological and behavioral tests.
Human subjects, non-human primates and rodents (including transgenic models) exposed to maternal stress, glucocorticoids or undernutrition will be examined.
- determine structural (MRI based volumetry) and functional (metabolomics, brain function, cerebrovascular tone) indicators of brain age,
- relate them to susceptibility to stroke and cognitive decline,
- determine to what extent GR resistance, stress sensitivity, and cerebrovascular contractility mediate premature brain ageing and disease susceptibility; and
- dissect mechanisms and pharmacological interventions which may be used in aged subjects.
Information obtained will allow identification of subjects at risk for premature brain ageing and offer therapeutic interventions.