Effects of chronic stress in pregnancy on hypothalamic gene expression patterns: interference with antidepressants and identified pathways

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Complex peripartum adaptations at neuroendocrine, neuronal and behavioural levels are well-established, which are necessary to prepare the mother for birth and motherhood. This includes attenuated glucocorticoid responsiveness, despite a concurrent basal hypercorticism, increased activity of the oxytocinergic system, onset of maternal behaviour, and anxiolysis. These changes are essential for both the healthy development of the offspring as well as for the maternal mental health. Disturbances of these adaptations, for example by chronic stress, are likely to increase the vulnerability of postpartum mood disorders, but underlying mechanisms are unknown. Data from the initial funding period demonstrate that chronic pregnancy stress (PS) in rat dams prevents these pregnancy- and lactation-associated adaptations.In continuation of these and recent results we first aim to fully characterize reproductionrelated alterations in gene expression patterns within the hypothalamic paraventricular nucleus (a region highly involved in maternal and stress adaptations), and how these gene expression patterns are altered by PS. In turn, pharmacological manipulation, or restoration by chronic antidepressant treatment, of neuronal target pathways/systems identified to be altered by PS would reveal their causal role in PS-induced maladaptations. The results will importantly increase our understanding of adaptive and maladaptive peripartum alterations for the first time at the genetic and cellular levels.