Effects of stress early in gestation on hippocampal neurogenesis and glucocorticoid receptor density in pregnant rats.

Pregnancy is a time of marked neural, physiological and behavioral plasticity in the female and is often a time when women are more vulnerable to stress and stress-related diseases, such as depression and anxiety. Unfortunately the impact of stress during gestation on neurobiological processes of the mother has yet to be fully determined, particularly with regard to changes in the hippocampus; a brain area that plays an important role in stress-related diseases. The present study aimed to determine how stress early in pregnancy may affect hippocampal plasticity in the pregnant female and whether these effects differ from those in virgin females. For this purpose, adult age-matched pregnant and virgin female Sprague-Dawley rats were divided into two conditions: (1) Control and (2) Stress. Females in the stress condition were restrained during days 5-11 of gestation and at matched time-points in virgin females. All pregnant females received an injection of bromodeoxyuridine (BrdU) on day 1 of gestation and were sacrificed 21 days later. The same procedure was carried out at matched time points in virgin females. Results show that for number of Ki67-immunoreactive (ir) cells and doublecortin (DCX)-ir cells, there were significant interactions between reproductive state (pregnant/virgin) and stress exposure (p=.05, p=.04, respectively) with control virgin and stressed pregnant females having more Ki67-ir cells than control pregnant females and more DCX-ir cells than stressed virgin females. Results also show that pregnant females had significantly greater glucocorticoid receptor (GR) density in the CA1, CA3 and granule cell layer compared to virgin females. In addition, there was a main effect of stress on GR density in the CA3 region, with stressed females having significantly lower GR density compared to control females (p=.01). This work adds to our understanding of how stress and reproductive state affect plasticity in the female hippocampus.