Veronika Spišská

Early-life exposure to light at night can disrupt the maturation of the circadian system and lead to long-lasting behavioural and molecular alterations. We exposed rat pups to constant light (LL; 16 lx) from birth (P0) to postnatal day 20, followed by a standard light–dark cycle (LD 12:12). At postnatal day 60, anxiety-like behaviour was assessed using the open field, elevated zero maze, and light/dark box. In parallel, we analysed circadian gene expression rhythms in the hippocampus, parietal cortex, frontal cortex, and olfactory bulbs, and examined A-to-I RNA editing and splicing in the hippocampus at P30. LL exposure increased body weight in males and tended to enhance anxiety-like behaviour, particularly in females. Locomotor activity during behavioural testing was reduced in both sexes, whereas circadian rhythms in constant darkness remained intact. At the molecular level, LL disrupted circadian gene expression in a brain region- and sex-specific manner. The hippocampus in males showed widespread loss of rhythmicity, while the parietal cortex was more affected in females. LL also reduced Adar2 expression rhythmicity and editing efficiency at functionally relevant sites in Gria2 and Htr2c, suggesting altered coupling between R/G editing and alternative splicing in Gria2. These findings demonstrate that low-intensity LL during a critical postnatal window can induce long-lasting, sex-specific alterations in behaviour and gene regulation. Our data provide the first mechanistic insight into how early environmental light exposure may shape long-term emotional and neurobiological outcomes.

In mammals, the suprachiasmatic nucleus (SCN) serves as the central circadian pacemaker, regulating rhythms essential for physiological processes. STAT3, a transcription factor primarily involved in immune signaling, exhibits circadian rhythmicity in SCN astrocytes. This study examined the role of STAT3 in circadian regulation across several cell types, including primary cultures of rat SCN and cortex, SCN cells and organotypic SCN slices from PER2::LUC mice, and C6 glioblastoma cells. Furthermore, the involvement of STAT3 in inflammatory responses was investigated in SCN and cortical primary cultures. STAT3 silencing enhanced Bmal1 expression across all tested cell types, disrupted Bmal1 rhythmicity in C6 cells, and reduced the amplitude of the PER2‐driven rhythm in bioluminescence in SCN primary cells and organotypic cultures. In SCN cells, STAT3 silencing also attenuated its own expression and Gfap , whereas in cortical cells, it exhibited broader effects. Under LPS stimulation, STAT3 silencing in SCN cells reduced most LPS‐induced genes, including inflammatory and oxidative stress markers, while showing variable effects in cortical cells. These findings indicate that while the role of STAT3 in the circadian clockwork appears consistent across cell types, its involvement in functional gene expression and immune responses may vary depending on the tissue and differ between SCN and cortical primary cells.

Circadian clocks regulate multiple physiological domains from molecular to behavioral levels and adjust bodily physiology to seasonal changes in day length. Circadian regulation of cellular bioenergy and immunity in the cardiovascular and muscle systems may underpin the individual diurnal differences in performance capacity during exercise. Several studies have shown diurnal differences in cardiopulmonary parameters at maximal and submaximal workloads in morning and evening circadian human phenotypes. However, the effect of seasons on these changes was not elucidated. In this study, we recruited subjects with Morningness–Eveningness Questionnaire scores corresponding to morning and evening types. Subjects underwent morning (7:00–9:00) and evening (20:00–22:00) maximal workload spiroergometry in both winter and summer seasons. We analyzed their performance time, anaerobic threshold, heart rate, and respiratory parameters. Our results suggest that evening types manifest diurnal variations in physical performance, particularly in winter. They also have slower heart rate recovery than morning types, irrespective of the time of day or season. Compared to winter, the chronotype effect on the magnitude of morning–evening differences in performance time, maximal heart rate, and anaerobic threshold onset was more significant in summer. Our data are in concordance with previous observations and confirm the difference between morning and evening types in the timing of maximum performance capacity.

The intrinsic period of circadian clock in the suprachiasmatic nucleus is entrained to a 24-h cycle by external cues, mainly light. Previous studies have shown that light applied at night induces robust phosphorylation of extracellular-signal-regulated kinase that is necessary to process the light pulse into the phase shift of the clock phase. In this study, we show the persistent downregulation of phosphorylated extracellular-signal-regulated kinase and transient downregulation of phosphorylated glycogen synthase kinase-3beta in the ventrolateral part of the suprachiasmatic nucleus to photic stimuli starting at 2 h after the beginning of the light pulse. As both kinases are involved in regulation of circadian clockwork, we hypothesize that these changes may contribute to the phase-shifting effect of light at night.