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.

Prenatal stress and subsequent exposure to chronic mild stress in rats; interdependent effects on emotional behavior and the serotonergic system.

Exposure to prenatal stress (PS) can predispose individuals to the development of psychopathology later in life. We examined the effects of unpredictable chronic mild stress (CMS) exposure during adolescence on a background of PS in male and female Sprague-Dawley rats. PS induced more anxiety-like behavior in the elevated zero maze in both sexes, an effect that was normalized by subsequent exposure to CMS. Moreover, PS was associated with increased depression-like behavior in the forced swim test in males only. Conversely, sucrose intake was increased in PS males, whilst being decreased in females when consecutively exposed to PS and CMS. Hypothalamo-pituitary-adrenal (HPA) axis reactivity was affected in males only, with higher stress-induced plasma corticosterone levels after PS. Markedly, CMS normalized the effects of PS on elevated zero maze behavior as well as basal and stress-induced plasma corticosterone secretion. At the neurochemical level, both PS and CMS induced various sex-specific alterations in serotonin (5-HT) and tryptophan hydroxylase 2 (TPH2) immunoreactivity in the dorsal raphe nucleus, hippocampus and prefrontal cortex with, in line with the behavioral observations, more profound effects in male offspring. In conclusion, these findings show that prenatal maternal stress in Sprague-Dawley rats induces various anxiety- and depression-related behavioral and neuroendocrine changes, as well as alterations in central 5-HT and TPH2 function, predominantly in male offspring. Moreover, CMS exposure partially normalized the effects of previous PS experience, suggesting that the outcome of developmental stress exposure largely depends on the environmental conditions later in life and vice versa.

Adrenalectomy and corticosterone replacement differentially alter CA3 dendritic morphology and new cell survival in the adult rat hippocampus.

Plastic changes in the adult mammal hippocampus can be altered by many factors and perhaps the most well-documented is stress. Stress and elevated corticosterone levels have been shown to decrease hippocampal neurogenesis and decrease the complexity of CA3 pyramidal neurons. However, the extent of these changes in relation to low and moderately elevated levels of corticosterone has yet to be fully investigated. Therefore, the aim of the present study was to determine how low to moderately elevated circulating corticosterone levels affect dendritic morphology of CA3 pyramidal cells and hippocampal neurogenesis in adult male rats. To do this, three groups of adult male Wistar rats were used: (1) Sham-operated, (2) Adrenalectomized (ADX), and (3) ADX+corticosterone replacement. Primary results show that adrenalectomy, but not moderately elevated levels of corticosterone replacement, resulted in significant atrophy of CA3 pyramidal neurons. Interestingly, moderate corticosterone replacement resulted in significantly more surviving new cells in the dentate gyrus when compared to sham controls. This work shows that circulating levels of corticosterone differentially affect plasticity in the CA3 region and the dentate gyrus.