PhD Scientific Days 2025

Poster Session I. - A: Molecular Medicine

Parallel Examination of Circadian Clock Function in Human Peripheral Tissues

Name of the presenter

Lumniczky Zalán

Institute/workplace of the presenter

Semmelweis University Department of Physiology

Authors

Zalán Lumniczky¹, Csongor György Szántó¹, Bianka Farkas¹, Tamás Kovács¹

1: Semmelweis University Department of Physiology

Text of the abstract

Aims: The circadian rhythm of an organism enables adequate adaptation to the rhythmic changes in the environment. All nucleated mammalian cells are believed to possess the molecular machinery required for circadian timekeeping. The mammalian circadian system is often likened to an orchestra, with the suprachiasmatic nuclei in the hypothalamus acting as the conductors and the peripheral tissue clocks as the musicians. Our knowledge is rather incomplete regarding how the functioning of peripheral clocks relates to each other and what factors mediate the influence of the central clock on them.
In this study, we aimed to examine possible correlations between two peripheral tissues and the master clock in humans.
Methods: We collected blood and buccal mucosa samples from 12 human subjects six times over a 24-hour period (9:30, 13:00, 16:30, 20:00, 23:30, and 6:00). Leukocyte counts and plasma cortisol concentrations were measured, and peripheral blood mononuclear cells (PBMCs) were isolated from the blood samples. RNA was isolated from PBMCs and mucosa samples, and the expression of clock genes (dbp, per2, and reverb-a) was analyzed. Core body temperature was monitored throughout the day, and overnight melatonin (aMT6S) excretion was measured. Chronotype was determined using the Munich Chronotype Questionnaire. For statistical analysis of circadian oscillations, we used cosinor analysis in R.
Results: We established an efficient method for isolating high-quality RNA from buccal mucosa. Significant daily oscillations of reverb-a were detected in both PBMCs and mucosa cells. Plasma cortisol levels, core body temperature, and leukocyte counts showed rhythmic changes. A phase difference of approximately 12 hours in clock gene expression between the two peripheral tissues was observed. The acrophase of the peripheral clocks varied across individuals, while rhythm parameters influenced by the master clock were much more consistent.
Conclusions: Our data suggest that social constraints have a dominant effect on the phase of the master clock. Surprisingly, the clock genes in different human peripheral tissues of the same individual oscillate at distinct phases.
Funding:
EKÖP-2024
STIA-2025