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Impact of Prenatal Stress on BRAIN AGEing

Impact of Prenatal Stress on BRAIN AGEing

Objective

Healthy brain ageing is a major determinant of quality life-long health, allowing 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: (1) prenatal stress programs early brain ageing; (2) this predisposes to age-associated brain diseases including cognitive decline and stroke; (3) epigenetic changes affecting glucocorticoid receptor (GR) sensitivity, altered autonomic nervous system (ANS) reactivity and cerebrovascular tone are important mediators of these processes, (4) 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 25-115 y equivalents) that have been exposed to different types of prenatal stress. For experimental analysis of mechanisms of prenatal programming, we apply 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 are examined in order to: (1) determine structural (MRI based volumetry) and functional (metabolomics, brain function, cerebrovascular tone) indicators of brain age, (2) relate them to susceptibility to stroke and cognitive decline, (3) determine to what extent GR resistance, stress sensitivity, and cerebrovascular contractility mediate premature brain ageing and disease susceptibility; and, (4) dissect mechanisms and pharmacological interventions relevant for aged subjects. Data from the study allow to identify subjects at risk for premature brain ageing and to initiate interventional therapy.

Coordinator

Universitätsklinikum Jena

Address

BachstraSSE 18
07743 Jena

Germany

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 076 295,60

Administrative Contact

Matthias Schwab (Prof.)

Participants (9)

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LEIBNIZ-INSTITUT FUR ALTERNSFORSCHUNG - FRITZ-LIPMANN-INSTITUT EV (FLI) LEIBNIZ INSTITUTE ON AGING - FRITZ LIPMANN INSTITUTE EV (FLI)

Germany

EU Contribution

€ 269 544

KATHOLIEKE UNIVERSITEIT LEUVEN

Belgium

EU Contribution

€ 71 428,80

THE UNIVERSITY OF TEXAS SYSTEM

United States

EU Contribution

€ 271 766,25

BIOCRATES LIFE SCIENCES AG

Austria

EU Contribution

€ 303 585,60

Academisch Medisch Centrum bij de Universiteit van Amsterdam

Netherlands

EU Contribution

€ 355 542,40

LIFE LENGTH SL

Spain

EU Contribution

€ 115 800

STICHTING KATHOLIEKE UNIVERSITEIT BRABANT

Netherlands

EU Contribution

€ 217 279,20

UNIVERSITAET ULM

Germany

EU Contribution

€ 216 144

UNIVERSITY OF WYOMING

United States

EU Contribution

€ 101 034,15

Project information

Grant agreement ID: 279281

Status

Closed project

  • Start date

    1 March 2012

  • End date

    28 February 2017

Funded under:

FP7-HEALTH

  • Overall budget:

    € 3 880 676,80

  • EU contribution

    € 2 998 420

Coordinated by:

Universitätsklinikum Jena

Germany