Circadian Clock Genes Are Regulated by Rhythmic Corticosterone at Physiological Levels in the Rat Hippocampus

Abstract

Plain Language SummaryAll mammals, including humans, have an internal 24 h biological clock enabling us to synchronize and optimize our physiology to daily life. The 24 h circadian clock of body is localized in neurons of the suprachiasmatic nucleus (SCN) located in the hypothalamus of the brain and is characterized by rhythmic activity of special clock genes. Circadian 24 h rhythms are present throughout the brain, including the hippocampus, where clock genes seem to be important for memory and mood. However, the signaling mechanism controlling circadian clock gene rhythms in the hippocampus is unknown. We hypothesized that oscillations of clock genes in the hippocampus could be driven by a well-established SCN-controlled circadian rhythm in glucocorticoid hormones from the adrenal glands, known as stress hormone or cortisol in humans and corticosterone in rodents. To test this hypothesis, we generated a rat surgical animal model, in which the SCN and adrenal glands were removed and a 24 h exogenous corticosterone rhythm at normal physiological levels was reestablished by use of an implanted programmable infusion pump. Removal of the SCN efficiently abolished clock gene rhythms in the hippocampus; however, reintroducing the natural glucocorticoid rhythm led to reestablishment of 24 h activity rhythms in hippocampal clock genes. Thus, our data suggest that rhythmic hormone release from the adrenal glands drives hippocampal clock gene rhythms and therefore provides a dynamic 24 h hormonal link between the circadian clock of the SCN and circadian function of the hippocampus.