The circadian phase of antenatal glucocorticoid treatment affects the risk of behavioral disorders

During pregnancy, maternal endocrine signals drive fetal development and program the offspring's physiology. A disruption of maternal glucocorticoid (GC) homeostasis increases the child's risk of developing psychiatric disorders later in life. We here show in mice, that the time of day of antenatal GC exposure predicts the behavioral phenotype of the adult offspring. Offspring of mothers receiving GCs out-of-phase compared to their endogenous circadian GC rhythm show elevated anxiety, impaired stress coping, and dysfunctional stress-axis regulation. The fetal circadian clock determines the vulnerability of the stress axis to GC treatment by controlling GC receptor (GR) availability in the hypothalamus. Similarly, a retrospective observational study indicates poorer stress compensatory capacity in 5-year old preterm infants whose mothers received antenatal GCs towards the evening. Our findings offer insights into the circadian physiology of feto-maternal crosstalk and assign a role to the fetal clock as a temporal gatekeeper of GC sensitivity

Signal Transduction Pathways in Ageing

It is now widely recognised that ageing and its associated functional decline are regulated by a wide range of molecules that fit into specific cellular pathways. Here, we describe several of the evolutionary conserved cellular signalling pathways that govern organismal ageing and discuss how their identification, and work on the individual molecules that contribute to them, has aided in the design of therapeutic strategies to alleviate the adverse effects of ageing and age-related disease