Preconception parental predator stress induces brain and behavioral changes in offspring

Brain and behaviour are shaped by experience. Recent data suggest that experiences of the parents can be ‘passed-on’ to alter brain and behavior of future generations. Stress during the preconception period is a new topic of interest, as it involves both prospective parents. The current study examined how parental preconception predator stress impacts the development of offspring brain and behaviour throughout its lifespan. Male and female mice (F0) were exposed to a live rat (rat exposure test) or control condition (no live rat exposure) for five minutes. Two days later, all mice underwent the elevated plus maze to assess anxiety-like behavior. Eight days later (a total of 10 days post predator exposure), stressed males were mated to stressed females and control males were mated to control females. Behavior of the offspring (F1) was assessed during adolescence and again in adulthood (following a mild stressor). F0 and F1 brains were examined for stress-induced changes in glucocorticoid receptors (GR), FK506 binding protein 5 (FKBP5), doublecortin, and c-FOS. Following a mild stressor, preconception stressed offspring show increased anxiety-like behavior, hyperarousal, and deficits in spatial memory. These mice also show elevated plasma corticosterone and altered GR, FKBP5 and c-FOS expression in the hippocampus. Furthermore, following a mild stressor, offspring (F2 generation) with at least one set of grandparents who were predator stressed showed increased anxiety-like behavior, enhanced hyperarousal, and deficits in spatial memory compared to offspring whose both sets of grandparents were controls. Despite the high incidence and potentially tragic outcome, there is little research on neural mechanisms underlying stress-induced disorders such as posttraumatic stress disorder (PTSD). These results may contribute to identifying at-risk individuals, as well as point to potential novel therapies for these devastating disorders