Synergistic Effects of Ancestral Stress and Aging on Anxiety-like Behaviours

Abstract

Exposure to adverse environments such as prenatal stress early in life is associated with anxiety-like behaviours in adulthood, which is potentially further exacerbated by aging. Recent studies have indicated that ancestral prenatal stress can propagate across generations to alter emotional wellbeing of unexposed offspring. Here we investigated if exposure to prenatal stress in the great-grandmother (transgenerational stress), or exposure across four consecutive generations (multigenerational stress) can alter anxiety-like behaviours in male and female fourth (F4) generation offspring. Anxiety-like behaviours were evaluated by means of the elevated plus maze in both males and females across three different groups: transgenerational stress (SNNN), multigenerational stress (SSSS), and non-stressed controls (NNNN). Both sexes were evaluated at the age of 12 months (middle age) and 18 months (old age). Our results demonstrate that aging and ancestral stress synergistically heightened anxiety-like behaviour, especially in males. Interestingly, the highest levels of anxiety-like behaviours were observed in transgenerationally stressed offspring of both ages. Overall, these results indicate that males are more sensitive to ancestral stress and more likely to respond by developing anxiety-like behaviours. Thus, ancestral stress and aging may synergistically alter mental health outcomes particularly in males.

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