activity rhythms
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The circadian clock in choroid plexus (ChP) controls processes involved in its physiological functions, but the signals that synchronize the clock have been sparsely studied. We found that the ChP clock in the fourthventricle (4V) is more robust than that in the lateral ventricle (LV) and investigated whether both clocks use information about mealtime as a signal to synchronize with the current activity state. Exposure of mPer2Luc mice to a 10-day reverse restricted feeding (rRF) protocol, in which food was provided for 6 h during daytime, advanced the phase of the ChP clock in 4V and LV, as evidenced by shifted (1) PER2-driven bioluminescence rhythms of ChP explants ex vivo and (2) daily profiles in clock gene expression in both ChP tissues in vivo. In contrast, clocks in other brain regions (DMH, ARC, LHb) of the same mice did not shift. The 4V ChP responded more strongly than the LV ChP to rRF by modulating the expression of genes to ensure a decrease in resistance to cerebrospinal fluid drainage and increase the secretory capacity of ChP cells. Mechanistically, rRF affects the ChP clock through food-induced increases in insulin, glucose and temperature levels, as in vitro all three signals significantly shifted the clocks in both ChP tissues, similar to rRF. The effect of glucose was partially blocked by OSMI-1, suggesting involvement of O-linked N-acetylglucosamine posttranslational modification. We identified mechanisms that can signal to the brain the time of feeding and the associated activity state via resetting of the ChP clock.
- MeSH
- cirkadiánní hodiny * fyziologie genetika MeSH
- cirkadiánní proteiny Period metabolismus genetika MeSH
- cirkadiánní rytmus fyziologie MeSH
- myši inbrední C57BL MeSH
- myši transgenní MeSH
- myši MeSH
- plexus chorioideus * metabolismus fyziologie MeSH
- regulace genové exprese MeSH
- stravovací zvyklosti * fyziologie MeSH
- ventriculi laterales metabolismus fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Řeč, pohyb, správný ontogenetický vývoj jedince, kognice, emoce, schopnost učit se, paměť – a s výčtem bychom mohly pokračovat. To vše je přímo závislé na rovnováze, za kterou stojí rytmus realizovaný v optimálním tempu s dostatečnou intenzitou a v pravidelně se opakujících, časově dobře volených intervalech. Často si, vlivem zautomatizovaných činností, neuvědomujeme, s jakou pravidelností, plánováním a organizovaností vykonáváme základní motorické vzorce, které se intuitivně a naprosto přirozeně učíme prostřednictvím dostatečně intenzivních intervalových rytmických aktivit. A právě terapie v logopedické praxi vedená intenzivně a intervalově napomáhá u dětí a žáků příznivě ovlivňovat prognózu jejich řečového vývoje, bez ohledu na to, zda využíváme direktivní, nebo nedirektivní přístup. To je mimo jiné potvrzeno také v závěru uvedeným stručným kazuistickým příkladem klientky se závažnou myofunkční poruchou.
Speech, movement, proper ontogenetic development of the individual, cognition, emotions, ability to learn, memory and the list could go on. All of these are directly dependent on balance, which is based on the rhythm realised at an optimal pace with sufficient intensity and in regularly recurring intervals of well-chosen timing. Often, due to automated activities, we are not aware of the regularity, planning and organisation with which we perform the basic motor patterns that we intuitively and quite naturally learn through sufficiently intense interval rhythmic activities. And it is precisely the therapy in Speech Therapy practice conducted intensively and at intervals, that helps to positively influence the prognosis of children and pupils in their speech development, regardless of whether we use a directive or non-directive approach. This is confirmed, among other things, by the brief case example of a client with a severe myofunctional disorder, presented in the end of the paper.
AIM: Exposure to light at night and meal time misaligned with the light/dark (LD) cycle-typical features of daily life in modern 24/7 society-are associated with negative effects on health. To understand the mechanism, we developed a novel protocol of complex chronodisruption (CD) in which we exposed female rats to four weekly cycles consisting of 5-day intervals of constant light and 2-day intervals of food access restricted to the light phase of the 12:12 LD cycle. METHODS: We examined the effects of CD on behavior, estrous cycle, sleep patterns, glucose homeostasis and profiles of clock- and metabolism-related gene expression (using RT qPCR) and liver metabolome and lipidome (using untargeted metabolomic and lipidomic profiling). RESULTS: CD attenuated the rhythmic output of the central clock in the suprachiasmatic nucleus via Prok2 signaling, thereby disrupting locomotor activity, the estrous cycle, sleep patterns, and mutual phase relationship between the central and peripheral clocks. In the periphery, CD abolished Per1,2 expression rhythms in peripheral tissues (liver, pancreas, colon) and worsened glucose homeostasis. In the liver, it impaired the expression of NAD+, lipid, and cholesterol metabolism genes and abolished most of the high-amplitude rhythms of lipids and polar metabolites. Interestingly, CD abolished the circadian rhythm of Cpt1a expression and increased the levels of long-chain acylcarnitines (ACar 18:2, ACar 16:0), indicating enhanced fatty acid oxidation in mitochondria. CONCLUSION: Our data show the widespread effects of CD on metabolism and point to ACars as biomarkers for CD due to misaligned sleep and feeding patterns.
- MeSH
- cirkadiánní hodiny fyziologie MeSH
- cirkadiánní rytmus * fyziologie MeSH
- fotoperioda MeSH
- játra * metabolismus MeSH
- karnitin * analogy a deriváty metabolismus MeSH
- krysa rodu rattus MeSH
- metabolom * MeSH
- nucleus suprachiasmaticus metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Temporal interference stimulation (TIS) is a novel noninvasive electrical stimulation technique to focally modulate deep brain regions; a minimum of two high-frequency signals (f1 and f2 > 1 kHz) interfere to create an envelope-modulated signal at a deep brain target with the frequency of modulation equal to the difference frequency: Δf = |f2 - f1|. OBJECTIVE: The goals of this study were to verify the capability of TIS to modulate the subthalamic nucleus (STN) with Δf and to compare the effect of TIS and conventional deep brain stimulation (DBS) on the STN beta oscillations in patients with Parkinson's disease (PD). METHODS: DBS leads remained externalized after implantation, allowing local field potentials (LFPs) recordings in eight patients with PD. TIS was performed initially by two pairs (f1 = 9.00 kHz; f2 = 9.13 kHz, 4 mA peak-peak per pair maximum) of scalp electrodes placed in temporoparietal regions to focus the envelope signal maximum (Δf = 130 Hz) at the motor part of the STN target. RESULTS: The comparison between the baseline LFPs and recordings after TIS and conventional DBS sessions showed substantial suppression of high beta power peak after both types of stimulation in all patients. CONCLUSIONS: TIS has the potential to effectively modulate the STN and reduce the beta oscillatory activity in a completely noninvasive manner, as is traditionally possible only with intracranial DBS. Future studies should confirm the clinical effectiveness of TIS and determine whether TIS could be used to identify optimal DBS candidates and individualize DBS targets. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
- MeSH
- beta rytmus EEG * fyziologie MeSH
- hluboká mozková stimulace * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- nucleus subthalamicus * patofyziologie MeSH
- Parkinsonova nemoc * terapie patofyziologie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Cellular senescence precipitates a decline in physiological activities and metabolic functions, often accompanied by heightened inflammatory responses, diminished immune function, and impaired tissue and organ performance. Despite extensive research, the mechanisms underpinning cellular senescence remain incompletely elucidated. Emerging evidence implicates circadian rhythm and hypoxia as pivotal factors in cellular senescence. Circadian proteins are central to the molecular mechanism governing circadian rhythm, which regulates homeostasis throughout the body. These proteins mediate responses to hypoxic stress and influence the progression of cellular senescence, with protein Brain and muscle arnt-like 1 (BMAL1 or Arntl) playing a prominent role. Hypoxia-inducible factor-1α (HIF-1α), a key regulator of oxygen homeostasis within the cellular microenvironment, orchestrates the transcription of genes involved in various physiological processes. HIF-1α not only impacts normal circadian rhythm functions but also can induce or inhibit cellular senescence. Notably, HIF-1α may aberrantly interact with BMAL1, forming the HIF-1α-BMAL1 heterodimer, which can instigate multiple physiological dysfunctions. This heterodimer is hypothesized to modulate cellular senescence by affecting the molecular mechanism of circadian rhythm and hypoxia signaling pathways. In this review, we elucidate the intricate relationships among circadian rhythm, hypoxia, and cellular senescence. We synthesize diverse evidence to discuss their underlying mechanisms and identify novel therapeutic targets to address cellular senescence. Additionally, we discuss current challenges and suggest potential directions for future research. This work aims to deepen our understanding of the interplay between circadian rhythm, hypoxia, and cellular senescence, ultimately facilitating the development of therapeutic strategies for aging and related diseases.
- MeSH
- cílená molekulární terapie MeSH
- cirkadiánní rytmus * fyziologie MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa metabolismus MeSH
- hypoxie buňky MeSH
- hypoxie metabolismus patofyziologie MeSH
- lidé MeSH
- signální transdukce MeSH
- stárnutí buněk * MeSH
- transkripční faktory ARNTL metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Working memory (WM) is essential for the temporary storage and processing of information required for complex cognitive tasks and relies on neuronal theta and gamma oscillations. Given the limited capacity of WM, researchers have investigated various methods to improve it, including transcranial alternating current stimulation (tACS), which modulates brain activity at specific frequencies. One particularly promising approach is theta-gamma peak-coupled-tACS (TGCp-tACS), which simulates the natural interaction between theta and gamma oscillations that occurs during cognitive control in the brain. The aim of this study was to improve WM in healthy young adults with TGCp-tACS, focusing on both behavioral and neurophysiological outcomes. Thirty-one participants completed five WM tasks under both sham and verum stimulation conditions. Electroencephalography (EEG) recordings before and after stimulation showed that TGCp-tACS increased power spectral density (PSD) in the high-gamma region at the stimulation site, while PSD decreased in the theta and delta regions throughout the cortex. From a behavioral perspective, although no significant changes were observed in most tasks, there was a significant improvement in accuracy in the 14-item Sternberg task, indicating an improvement in phonological WM. In conclusion, TGCp-tACS has the potential to promote and improve the phonological component of WM. To fully realize the cognitive benefits, further research is needed to refine the stimulation parameters and account for individual differences, such as baseline cognitive status and hormonal factors.
- MeSH
- chování fyziologie MeSH
- dospělí MeSH
- elektrická stimulace MeSH
- elektroencefalografie MeSH
- gama rytmus EEG fyziologie MeSH
- krátkodobá paměť * fyziologie MeSH
- lidé MeSH
- mladý dospělý MeSH
- přímá transkraniální stimulace mozku * metody MeSH
- theta rytmus EEG fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Aging encompasses a wide array of detrimental effects that compromise physiological functions, elevate the risk of chronic diseases, and impair cognitive abilities. However, the precise underlying mechanisms, particularly the involvement of specific molecular regulatory proteins in the aging process, remain insufficiently understood. Emerging evidence indicates that c-Jun N-terminal kinase (JNK) serves as a potential regulator within the intricate molecular clock governing aging-related processes. JNK demonstrates the ability to diminish telomerase reverse transcriptase activity, elevate β-galactosidase activity, and induce telomere shortening, thereby contributing to immune system aging. Moreover, the circadian rhythm protein is implicated in JNK-mediated aging. Through this comprehensive review, we meticulously elucidate the intricate regulatory mechanisms orchestrated by JNK signaling in aging processes, offering unprecedented molecular insights with significant implications and highlighting potential therapeutic targets. We also explore the translational impact of targeting JNK signaling for interventions aimed at extending healthspan and promoting longevity.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
N6-methyladenosine (m6A) is the most abundant epitranscriptomic mark that regulates the fate of RNA molecules. Recent studies have revealed a bidirectional interaction between m6A modification and the circadian clock. However, the precise temporal dynamics of m6A global enrichment in the central circadian pacemaker have not been fully elucidated. Our study investigates the relationship between FTO demethylase and molecular clocks in primary cells of the suprachiasmatic nucleus (SCN). In addition, we examined the effects of lipopolysaccharide (LPS) on Fto expression and the role of FTO in LPS-induced reactive oxygen species (ROS) production in primary SCN cell culture. We observed circadian rhythmicity in the global m6A levels, which mirrored the rhythmic expression of the Fto demethylase. Silencing FTO using siRNA reduced the mesor of Per2 rhythmicity in SCN primary cells and extended the period of the PER2 rhythm in SCN primary cell cultures from PER2::LUC mice. When examining the immune response, we discovered that exposure to LPS upregulated global m6A levels while downregulating Fto expression in SCN primary cell cultures. Interestingly, we found a loss of circadian rhythmicity in Fto expression following LPS treatment, indicating that the decrease of FTO levels may contribute to m6A upregulation without directly regulating its circadian rhythm. To explore potential protective mechanisms against neurotoxic inflammation, we examined ROS production following LPS treatment in SCN primary cell cultures pretreated with FTO siRNA. We observed a time-dependent pattern of ROS induction, with significant peak at 32 h but not at 20 h after synchronization. Silencing the FTO demethylase abolished ROS induction following LPS exposure, supporting the hypothesis that FTO downregulation serves as a protective mechanism during LPS-induced neuroinflammation in SCN primary cell cultures.
- MeSH
- adenosin * analogy a deriváty metabolismus MeSH
- cirkadiánní hodiny * účinky léků fyziologie genetika MeSH
- cirkadiánní proteiny Period metabolismus genetika MeSH
- cirkadiánní rytmus účinky léků fyziologie MeSH
- gen pro FTO * metabolismus genetika MeSH
- kultivované buňky MeSH
- lipopolysacharidy * farmakologie MeSH
- methylace RNA MeSH
- metylace účinky léků MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- neurozánětlivé nemoci metabolismus MeSH
- nucleus suprachiasmaticus * metabolismus účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- RNA genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The topic of human circadian rhythms is not only attracting the attention of clinical researchers from various fields but also sparking a growing public interest. The circadian system comprises the central clock, located in the suprachiasmatic nucleus of the hypothalamus, and the peripheral clocks in various tissues that are interconnected; together they coordinate many daily activities, including sleep and wakefulness, physical activity, food intake, glucose sensitivity and cardiovascular functions. Disruption of circadian regulation seems to be associated with metabolic disorders (particularly impaired glucose tolerance) and cardiovascular disease. Previous clinical trials revealed that disturbance of the circadian system, specifically due to shift work, is associated with an increased risk of type 2 diabetes mellitus. This review is intended to provide clinicians who wish to implement knowledge of circadian disruption in diagnosis and strategies to avoid cardio-metabolic disease with a general overview of this topic.
- MeSH
- chronobiologické poruchy patofyziologie komplikace MeSH
- cirkadiánní rytmus * fyziologie MeSH
- diabetes mellitus 2. typu patofyziologie metabolismus MeSH
- kardiovaskulární nemoci * etiologie patofyziologie MeSH
- lidé MeSH
- metabolické nemoci * patofyziologie metabolismus etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Our circadian world shapes much of metabolic physiology. In mice ∼40% of the light and ∼80% of the dark phase time is characterized by bouts of increased energy expenditure (EE). These ultradian bouts have a higher body temperature (Tb) and thermal conductance and contain virtually all of the physical activity and awake time. Bout status is a better classifier of mouse physiology than photoperiod, with ultradian bouts superimposed on top of the circadian light/dark cycle. We suggest that the primary driver of ultradian bouts is a brain-initiated transition to a higher defended Tb of the active/awake state. Increased energy expenditure from brown adipose tissue, physical activity, and cardiac work combine to raise Tb from the lower defended Tb of the resting/sleeping state. Thus, unlike humans, much of mouse metabolic physiology is episodic with large ultradian increases in EE and Tb that correlate with the active/awake state and are poorly aligned with circadian cycling.
- MeSH
- bdění fyziologie MeSH
- cirkadiánní rytmus * fyziologie MeSH
- energetický metabolismus * fyziologie MeSH
- fotoperioda * MeSH
- hnědá tuková tkáň metabolismus fyziologie MeSH
- myši MeSH
- spánek fyziologie MeSH
- tělesná teplota * fyziologie MeSH
- ultradiánní rytmus * fyziologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
