Sex-Specific Effects of Ancestral Stress on Brain Health and Disease Across the Lifespan

Abstract

Early life stress alters fetal brain development with lifetime consequences on individuals exposed and future generations. This thesis investigated the effects of ancestral stress on behaviour, brain aging, and disease incidence of the F1-F4 generation offspring. Two types of ancestral stress offspring were examined: transgenerational stress, where only great-great grandma was stressed and mutigenerational stress where four consecutive F0-F3 generations were stressed during pregnancy. Here were report three main findings: 1) ancestral stress induced sex-specific anxiety-like behaviour and brain plasticity through altered epigenetic regulation; 2) the effects of ancestral stress persisted across the lifespan, altered physical and mental health and increased risk of disease; and 3) social isolation stress altered stress and immune systems and contributed to sex-specific cognitive impairments. These findings contribute to the overall understanding of the perinatal origins of healthy brain aging and disease, and address the urgent need of recommendations to support healthy aging worldwide.