Ultradian rhythms of AKT phosphorylation and gene expression emerge in the absence of the circadian clock components Per1 and Per2

Rhythmicity of biological processes can be elicited either in response to environmental cycles or driven by endogenous oscillators. In mammals, the circadian clock drives about 24-hour rhythms of multitude metabolic and physiological processes in anticipation to environmental daily oscillations. Also at the intersection of environment and metabolism is the protein kinase—AKT. It conveys extracellular signals, primarily feeding-related signals, to regulate various key cellular functions. Previous studies in mice identified rhythmicity in AKT activation (pAKT) with elevated levels in the fed state. However, it is still unknown whether rhythmic AKT activation can be driven through intrinsic mechanisms. Here, we inspected temporal changes in pAKT levels both in cultured cells and animal models. In cultured cells, pAKT levels showed circadian oscillations similar to those observed in livers of wild-type mice under free-running conditions. Unexpectedly, in livers of Per1,2−/− but not of Bmal1−/− mice we detected ultradian (about 16 hours) oscillations of pAKT levels. Importantly, the liver transcriptome of Per1,2−/− mice also showed ultradian rhythms, corresponding to pAKT rhythmicity and consisting of AKT-related genes and regulators. Overall, our findings reveal ultradian rhythms in liver gene expression and AKT phosphorylation that emerge in the absence of environmental rhythms and Per1,2−/− genes.

Regulation of high-frequency rhythms of the behavioral activity by oligopeptides structurаlly related to oxytocin

The pharmacological regulation of high-frequency rhythms of the behavioral activity (with a period of up to 1/2 hour) is an actual direction of modern medical science. The aim of the study was to assess the influence of oligopeptides structurally related to oxytocin on the parameters of ultradian rhythms of locomotor activity (LA) in outbred ICR laboratory mice. LA was recorded automatically in a multichannel actometer (Ugo Basile, Italy) in the conditions of individual detection. Amplitude, acrophase, and mesor of biorhythms’ were determined by the Cosinor analysis. Oligopeptides structurally related to oxytocin fragments, as well as memantine under systemic (intraperitoneal) administration, had a pronounced influence on the ultradian LA biorhythms of mice. Memantine (10.0 mg/kg), Cyclo-(Leu-Gly) (0.025 mg/kg), Pro-Leu (0.5 mg/kg), and Leu-Gly (0.1 mg/kg) triggered the migration to the right of the acrophase of statistically significant 24-minute LA rhythms versus control. A further study of the peptidergic mechanisms of regulation of fluctuations in ultradian biorhythms can contribute to the development of the theoretical foundations of chronobiology, as well as to the search for the means correcting the desynchronoses.

Courtship rhythm in Nasonia vitripennis is affected by the clock gene period

The clock gene period (per) is a regulator of circadian rhythms but may also play a role in the regulation of ultradian rhythms, such as insect courtship. Males of the parasitoid wasp Nasonia vitripennis court females by performing series of head movements (‘head-nods’) and wing vibrations within repeated cycles. The pattern of cycle duration and head-nod number is species-specific and has a genetic basis. In this study, the possible involvement of per in regulating Nasonia courtship rhythms was investigated in a southern and northern European strain that differ in number and timing of courtship components. Knockdown of per via RNA interference (RNAi) resulted in a shortening of the circadian free running period (tau) in constant darkness (DD), and increased both the cycle duration and the number of head-nods per cycle in both strains. These results point at a role of per in the regulation of ultradian rhythms and male courtship behaviour of N. vitripennis and may contribute to resolving the controversy about the role of per in insect courtship behaviour.