Social stress during pregnancy programs the central neurosteroid system of the offspring

Paula Brunton, J.J. Paris, C. A. Frye, John Russell

Research output: Contribution to conferencePoster

Abstract

In rats, prenatal social stress (PNS; exposure to an unfamiliar aggressive lactating rat for 10 min/day on gestational days 16-20) results in exaggerated hypothalamo-pituitary-adrenal (HPA) axis responses to acute stressors and increased anxiety-like behaviour in the adult male offspring.
We previously found that peripheral administration of the 5α-reduced metabolite of testosterone (androstandiol) reversed the anxious and stress hyper-responsive phenotype in male PNS offspring. Here we tested whether male PNS rats have deficits in central neurosteroid production. We quantified basal expression of 5α-reductase (5αR) mRNA in the central nervous system of male control and PNS rats by in situ hybridisation and measured allopregnanolone concentrations in homogenates containing prefrontal cortex, hypothalamus, hippocampus, midbrain and cerebellum by radioimmunoassay.
5αR mRNA levels were significantly lower in PNS rats compared with controls in brain regions that provide excitatory drive to the HPA axis, such as the paraventricular nucleus and nucleus tractus solitarii. Conversely, 5αR mRNA was significantly greater in PNS males compared with controls in areas of the limbic system that exert an inhibitory influence over HPA axis activity, such as the prefrontal cortex and the dorsal lateral septum. Moreover, allopregnanolone concentrations were significantly lower in hypothalamic, midbrain and whole brain homogenates from PNS rats compared with controls. Lastly, correlation analysis revealed a significant inverse relationship between the level of aggression the dam experienced during the social stress in her pregnancy and whole brain allopregnanolone concentrations in the male PNS offspring.
Hence, altered neurosteroid production in the offspring’s brain as a result of stress exposure during pregnancy may explain HPA axis hyper-responsiveness and the increased anxiety-like behaviour observed in male prenatally programmed offspring.
Support: BBSRC
Original languageEnglish
Publication statusUnpublished - 2012
EventBritish Society for Neuroendocrinology Annual Meeting - Aberdeen, United Kingdom
Duration: 8 Jul 201210 Jul 2012

Conference

ConferenceBritish Society for Neuroendocrinology Annual Meeting
Country/TerritoryUnited Kingdom
CityAberdeen
Period8/07/1210/07/12

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