Speaker: Karolína Šuchmanová
Date: 2019.09.20 (Fri.) 15:00-17:00 pm
Location: 12F Conference room, Daan Campus, Taipei Medical University
The daily regulation of behavioral and physiological processes, including memory formation, is maintained by the circadian system, consisting of principal clock in the suprachiasmatic nuclei of the hypothalamus, and peripheral clocks. Peripheral circadian clock has also been found in the hippocampus, where it temporally regulates processes related to memory formation. However, little is still known about mechanisms synchronizing the clock with external cues. Therefore, our aim was to ascertain possible role of glucocorticoid hormones (GCs) in this process. The GCs are likely candidates because hippocampus is involved in their regulation and contains high levels of glucocorticoid receptors. To achieve this, we first investigated the impact of GCs absence on the hippocampal clock in vivo in Wistar rats. Expression profiles of clock genes Per1, Per2, Rev-erbα and Bmal1 were examined using RT-PCR. We found that absence of GCs abolished rhythmical clock gene expression in the hippocampus, and administration of GCs analog dexamethasone partly reversed this effect. Next, we measured responses of the clock to the GC stimulation in vitro using long-term cultivated organotypic hippocampal explants from Per2::LUC mice. The GC signaling directly influenced circadian rhythmicity of PER2 protein in vitro. The effect was dependent on time of GCs pathway stimulation and was inhibited by glucocorticoid receptor antagonist. These findings favor the role of GCs as hippocampal clock synchronizers. Our results provide insight into plausible mechanisms of hippocampal circadian clock dysfunction in neuropsychiatric disorders accompanied by abnormal glucocorticoid levels and memory impairment and should also be taken into consideration when administering systemic GC therapy.