The impact of maternal stress on offspring brain development

Paula J Brunton

Centre for Discovery Brain Sciences, University of Edinburgh, UK

Prenatal stress (PNS) can programme long-lasting neuroendocrine and behavioural changes in the offspring. Often this programming is maladaptive and sex-specific. For example, using a rat model of maternal social stress in late pregnancy, we have demonstrated that adult PNS male, but not PNS female, offspring display heightened anxiety-like behaviour; whereas both sexes show hyperactive hypothalamo-pituitary-adrenal (HPA) axis responses to stress.

I will present our current knowledge of the mechanisms underpinning dysregulated HPA axis responses in PNS offspring, including evidence supporting a role for reduced neurosteroid generation in the brains of both the male and female adult PNS offspring. Moreover, I will demonstrate that administration of neurosteroids or targeted up-regulation of central gene expression for neurosteroids-synthesising enzymes can normalise aberrant HPA axis stress responses in PNS offspring.

How the effects of maternal psychosocial stress are transmitted from the mother to the fetuses is unclear. Direct transfer of maternal glucocorticoids to the fetuses is often considered to mediate the programming effects of maternal stress on the offspring. However, protective mechanisms including attenuated maternal stress responses and placental 11β-hydroxysteroid dehydrogenase-2 (11βHSD2; which inactivates glucocorticoids), limit mother-to-fetus glucocorticoid transfer during pregnancy. Nonetheless, the placenta, at the maternal-fetal interface, it is likely to play a key role. Therefore we will explore the contribution of the placenta in signalling the stress status of the mother to the fetus and investigate whether interfering with this signalling can prevent the adverse offspring phenotypes induced by maternal psychosocial stress.