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1.
Cell Tissue Res ; 387(2): 261-274, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34816282

RESUMO

Circadian rhythms are those variations in behavioral and molecular processes of organisms that follow roughly 24 h cycles in the absence of any external cue. The hypothalamic suprachiasmatic nucleus (SCN) harbors the principal brain pacemaker driving circadian rhythms. The epithalamic habenula (Hb) contains a self-sustained circadian clock functionally coupled to the SCN. Anatomically, the Hb projects to the midbrain dopamine (DA) and serotonin (5-HT) systems, and it receives inputs from the forebrain, midbrain, and brainstem. The SCN is set by internal signals such as 5-HT or melatonin from the raphe nuclei and pineal gland, respectively. However, how the Hb clock is set by internal cues is not well characterized. Hence, in the present study, we determined whether DA, noradrenaline (NA), 5-HT, and the neuropeptides orexin (ORX) and vasopressin influence the Hb circadian clock. Using PER2::Luciferase transgenic mice, we found that the amplitude of the PER2 protein circadian oscillations from Hb explants was strongly affected by DA and NA. Importantly, these effects were dose-and region (rostral vs. caudal) dependent for NA, with a main effect in the caudal part of the Hb. Furthermore, ORX also induced a significant change in the amplitude of PER2 protein oscillations in the caudal Hb. In conclusion, catecholaminergic (DA, NA) and ORXergic transmission impacts the clock properties of the Hb clock likely contributing to the circadian regulation of motivated behaviors. Accordingly, pathological conditions that lead in alterations of catecholamine or ORX activity (drug intake, compulsive feeding) might affect the Hb clock and conduct to circadian disturbances.


Assuntos
Relógios Circadianos , Habenula , Animais , Catecolaminas/metabolismo , Ritmo Circadiano , Habenula/metabolismo , Camundongos , Camundongos Transgênicos , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Núcleo Supraquiasmático/metabolismo
2.
Cell Mol Biol Lett ; 27(1): 73, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064311

RESUMO

Melatonin is an important naturally occurring hormone in mammals. Melatonin-mediated biological effects include the regulation of circadian rhythms, which is important for optimal human health. Also, melatonin has a broad range of immunoenhancing actions. Moreover, its oncostatic properties, especially regarding breast cancer, involve a variety cancer-inhibitory processes and are well documented. Due to their promising effects on the prognosis of cancer patients, anti-cancer drugs with epigenetic actions have attracted a significant amount of attention in recent years. Epigenetic modifications of cancers are categorized into three major processes including non-coding RNAs, histone modification, and DNA methylation. Hence, the modification of the latter epigenetic event is currently considered an effective strategy for treatment of cancer patients. Thereby, this report summarizes the available evidence that investigated melatonin-induced effects in altering the status of DNA methylation in different cancer cells and models, e.g., malignant glioma and breast carcinoma. Also, we discuss the role of artificial light at night (ALAN)-mediated inhibitory effects on melatonin secretion and subsequent impact on global DNA methylation of cancer cells.


Assuntos
Neoplasias da Mama , Melatonina , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Ritmo Circadiano/genética , Metilação de DNA/genética , Epigênese Genética , Feminino , Humanos , Mamíferos , Melatonina/farmacologia , Melatonina/fisiologia , Melatonina/uso terapêutico
3.
Sleep Med Rev ; 64: 101667, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36064209

RESUMO

Light is a potent circadian entraining agent. For many people, daily light exposure is fundamentally dysregulated with reduced light during the day and increased light into the late evening. This lighting schedule promotes chronic disruption to circadian physiology resulting in a myriad of impairments. Developmental changes in sleep-wake physiology suggest that such light exposure patterns may be particularly disruptive for adolescents and further compounded by lifestyle factors such as early school start times. This narrative review describes evidence that reduced light exposure during the school day delays the circadian clock, and longer exposure durations to light-emitting electronic devices in the evening suppress melatonin. While home lighting in the evening can suppress melatonin secretion and delay circadian phase, the patterning of light exposure across the day and evening can have moderating effects. Photic countermeasures may be flexibly and scalably implemented to support sleep-wake health; including manipulations of light intensity, spectra, duration and delivery modality across multiple contexts. An integrative approach addressing physiology, attitudes, and behaviors will support optimization of light-driven sleep-wake outcomes in adolescents.


Assuntos
Relógios Circadianos , Melatonina , Adolescente , Ritmo Circadiano/fisiologia , Humanos , Iluminação , Sono/fisiologia
4.
PLoS Biol ; 20(9): e3001734, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36067166

RESUMO

Animals adequately modulate their physiological status and behavior according to the season. Many animals sense photoperiod for seasonal adaptation, and the circadian clock is suggested to play an essential role in photoperiodic time measurement. However, circadian clock-driven neural signals in the brain that convey photoperiodic information remain unclear. Here, we focused on brain extracellular dynamics of a classical neurotransmitter glutamate, which is widely used for brain neurotransmission, and analyzed its involvement in photoperiodic responses using the bean bug Riptortus pedestris that shows clear photoperiodism in reproduction. Extracellular glutamate levels in the whole brain were significantly higher under short-day conditions, which cause a reproductive diapause, than those under long-day conditions. The photoperiodic change in glutamate levels was clearly abolished by knockdown of the clock gene period. We also demonstrated that genetic modulation of glutamate dynamics by knockdown of glutamate-metabolizing enzyme genes, glutamate oxaloacetate transaminase (got) and glutamine synthetase (gs), attenuated photoperiodic responses in reproduction. Further, we investigated glutamate-mediated photoperiodic modulations at a cellular level, focusing on the pars intercerebralis (PI) neurons that photoperiodically change their neural activity and promote oviposition. Electrophysiological analyses showed that L-Glutamate acts as an inhibitory signal to PI neurons via glutamate-gated chloride channel (GluCl). Additionally, combination of electrophysiology and genetics revealed that knockdown of got, gs, and glucl disrupted cellular photoperiodic responses of the PI neurons, in addition to reproductive phenotypes. Our results reveal that the extracellular glutamate dynamics are photoperiodically regulated depending on the clock gene and play an essential role in the photoperiodic control of reproduction via inhibitory pathways.


Assuntos
Ácido Glutâmico , Fotoperíodo , Animais , Encéfalo/fisiologia , Ritmo Circadiano/genética , Feminino , Reprodução/genética
5.
Neurología (Barc., Ed. impr.) ; 37(7): 575-585, Sep. 2022. ilus
Artigo em Inglês, Espanhol | IBECS | ID: ibc-207480

RESUMO

La melatonina es la principal hormona implicada en la regulación de la oscilación entre sueño y vigilia. Es fácilmente sintetizable y administrable por vía oral, lo que ha propiciado el interés para usarla en el tratamiento de una de las patologías humanas más prevalentes, el insomnio. Además, el hecho de que su producción se reduzca con la edad, en una relación inversamente proporcional a la frecuencia de mala calidad de sueño, ha reforzado la idea de que su déficit es, al menos en parte, responsable de estos trastornos. En esta línea de pensamiento, remontar el déficit que se va instaurando a medida que transcurre la vida sería un modo natural de restaurar la integridad del sueño, que se va perdiendo con la edad. Sin embargo, a pesar del innegable atractivo teórico de esta aproximación al problema del insomnio, la evidencia científica que sustenta el posible beneficio de esta terapia sustitutiva es escasa. Ni siquiera están bien definidos los rangos de dosis a los que administrarla o la formulación farmacológica más adecuada. En la presente revisión se repasa la fisiología de la melatonina, se revisan las características farmacológicas de su administración exógena y se analizan los datos existentes sobre su utilidad clínica. (AU)


Melatonin is the main hormone involved in the control of the sleep-wake cycle. It is easily synthesisable and can be administered orally, which has led to interest in its use as a treatment for insomnia. Moreover, as production of the hormone decreases with age, in inverse correlation with the frequency of poor sleep quality, it has been suggested that melatonin deficit is at least partly responsible for sleep disorders. Treating this age-related deficit would therefore appear to be a natural way of restoring sleep quality, which is lost as patients age. However, despite the undeniable theoretical appeal of this approach to insomnia, little scientific evidence is available that supports any benefit of this substitutive therapy. Furthermore, the most suitable dose ranges and pharmaceutical preparations for melatonin administration are yet to be clearly defined. This review addresses the physiology of melatonin, the different pharmaceutical preparations, and data on its clinical usefulness. (AU)


Assuntos
Humanos , Melatonina , Ritmo Circadiano/efeitos dos fármacos , Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília
6.
Adv Exp Med Biol ; 1390: 143-153, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36107317

RESUMO

All life of Earth has evolved mechanisms to track time. This permits anticipation of predictable changes in light/dark, and in most cases also directs fed/fasted cycles, and sleep/wake. The nuclear receptors enjoy a close relationship with the molecular machinery of the clock. Some play a core role within the circadian machinery, other respond to ligands which oscillate in concentration, and physical cross-talk between clock transcription factors, eg cryptochromes, and multiple nuclear receptors also enable coupling of nuclear receptor function to time of day. Essential processes including inflammation, and energy metabolism are strongly regulated by both the circadian machinery, and rhythmic behaviour, and also by multiple members of the nuclear receptor family. An emerging theme is reciprocal regulation of key processes by different members of the nuclear receptor family, for example NR1D1/2, and NR1F1, in regulation of the core circadian clock transcription factor BMAL1.


Assuntos
Relógios Circadianos , Ritmo Circadiano , Fatores de Transcrição ARNTL/genética , Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Criptocromos/genética , Ligantes
7.
Neuron ; 110(17): 2728-2742, 2022 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-36076337

RESUMO

Prethalamic nuclei in the mammalian brain include the zona incerta, the ventral lateral geniculate nucleus, and the intergeniculate leaflet, which provide long-range inhibition to many targets in the midbrain, hindbrain, and thalamus. These nuclei in the caudal prethalamus can integrate sensory and non-sensory information, and together they exert powerful inhibitory control over a wide range of brain functions and behaviors that encompass most aspects of the behavioral repertoire of mammals, including sleep, circadian rhythms, feeding, drinking, predator avoidance, and exploration. In this perspective, we highlight the evidence for this wide-ranging control and lay out the hypothesis that one role of caudal prethalamic nuclei may be that of a behavioral switchboard that-depending on the sensory input, the behavioral context, and the state of the animal-can promote a behavioral strategy and suppress alternative, competing behaviors by modulating inhibitory drive onto diverse target areas.


Assuntos
Controle Comportamental , Corpos Geniculados , Animais , Ritmo Circadiano , Corpos Geniculados/fisiologia , Mamíferos , Mesencéfalo , Tálamo
8.
Cancer Discov ; 12(9): 2017-2019, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36052502

RESUMO

SUMMARY: Prostate tumors can develop resistance to androgen receptor (AR)-targeted therapies through treatment-induced changes in transcription factor activity that promote transcriptional and morphologic features of a neuroendocrine lineage. This study identifies an unexpected role for the circadian protein ARNTL in resistance to enzalutamide, a second-generation AR-targeted therapy. See related article by Linder et al., p. 2074 (4).


Assuntos
Androgênios , Neoplasias de Próstata Resistentes à Castração , Translocador Nuclear Receptor Aril Hidrocarboneto , Benzamidas , Ritmo Circadiano , Resistencia a Medicamentos Antineoplásicos/genética , Epigenômica , Humanos , Masculino , Nitrilas , Feniltioidantoína , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo
9.
J Hypertens ; 40(10): 2013-2021, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36052524

RESUMO

OBJECTIVES: Cold exposure accounts for more than 7% of all-cause mortality worldwide, and cold-induced blood pressure (BP) elevation and consequent cardiovascular events are partially responsible. For prevention, it is important to identify risk factors for exaggerated temperature-sensitivity of BP but this is not fully understood. This study investigated whether depressive symptoms affect the relationship between indoor temperature and BP. METHODS: We conducted a cross-sectional analysis of 1076 community-based individuals who were at least 60 years of age. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale at a cutoff point of 4/5. We performed ambulatory BP monitoring and indoor temperature measurement on two consecutive days during the cold season in Nara, Japan. RESULTS: When using daytime SBP as a dependent variable, multilevel linear regression analyses showed that lower daytime indoor temperature was significantly associated with higher daytime SBP in the depressive group (n = 216, ß = -0.804, P < 0.001) but not in the nondepressive group (n = 860, ß = -0.173, P = 0.120); moreover, a significant interaction between depression and daytime indoor temperature was observed (P = 0.014). These relationships were independent of potential confounders including age, gender, BMI, medications, and physical activity. Similar results were obtained for morning SBP, nocturnal SBP dipping, and morning BP surge. CONCLUSION: The results suggest that depressive participants are more likely to have cold-induced BP elevation than nondepressive participants. Further longitudinal studies are warranted to determine whether people with depressive symptoms are at a high risk for cold-related cardiovascular events.


Assuntos
Depressão , Hipertensão , Idoso , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Ritmo Circadiano/fisiologia , Estudos Transversais , Humanos , Temperatura
10.
Elife ; 112022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047761

RESUMO

Circadian rhythms are maintained by a cell-autonomous, transcriptional-translational feedback loop known as the molecular clock. While previous research suggests a role of the molecular clock in regulating skeletal muscle structure and function, no mechanisms have connected the molecular clock to sarcomere filaments. Utilizing inducible, skeletal muscle specific, Bmal1 knockout (iMSBmal1-/-) mice, we showed that knocking out skeletal muscle clock function alters titin isoform expression using RNAseq, liquid chromatography-mass spectrometry, and sodium dodecyl sulfate-vertical agarose gel electrophoresis. This alteration in titin's spring length resulted in sarcomere length heterogeneity. We demonstrate the direct link between altered titin splicing and sarcomere length in vitro using U7 snRNPs that truncate the region of titin altered in iMSBmal1-/- muscle. We identified a mechanism whereby the skeletal muscle clock regulates titin isoform expression through transcriptional regulation of Rbm20, a potent splicing regulator of titin. Lastly, we used an environmental model of circadian rhythm disruption and identified significant downregulation of Rbm20 expression. Our findings demonstrate the importance of the skeletal muscle circadian clock in maintaining titin isoform through regulation of RBM20 expression. Because circadian rhythm disruption is a feature of many chronic diseases, our results highlight a novel pathway that could be targeted to maintain skeletal muscle structure and function in a range of pathologies.


Assuntos
Relógios Circadianos , Doenças Musculares , Animais , Relógios Circadianos/genética , Ritmo Circadiano , Conectina/genética , Conectina/metabolismo , Camundongos , Músculo Esquelético/metabolismo , Doenças Musculares/patologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Quinases/metabolismo , Splicing de RNA , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
11.
Proc Natl Acad Sci U S A ; 119(37): e2202426119, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36067319

RESUMO

The cyanobacterial clock presents a unique opportunity to understand the biochemical basis of circadian rhythms. The core oscillator, composed of the KaiA, KaiB, and KaiC proteins, has been extensively studied, but a complete picture of its connection to the physiology of the cell is lacking. To identify previously unknown components of the clock, we used KaiB locked in its active fold as bait in an immunoprecipitation/mass spectrometry approach. We found that the most abundant interactor, other than KaiC, was a putative diguanylate cyclase protein predicted to contain multiple Per-Arnt-Sim (PAS) domains, which we propose to name KidA. Here we show that KidA directly binds to the fold-switched active form of KaiB through its N-terminal PAS domains. We found that KidA shortens the period of the circadian clock both in vivo and in vitro and alters the ability of the clock to entrain to light-dark cycles. The dose-dependent effect of KidA on the clock period could be quantitatively recapitulated by a mathematical model in which KidA stabilizes the fold-switched form of KaiB, favoring rebinding to KaiC. Put together, our results show that the period and amplitude of the clock can be modulated by regulating the access of KaiB to the fold-switched form.


Assuntos
Proteínas de Bactérias , Relógios Circadianos , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano , Ritmo Circadiano , Synechococcus , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/química , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/genética , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/metabolismo , Fosforilação , Domínios Proteicos , Synechococcus/fisiologia
12.
PLoS Comput Biol ; 18(9): e1010494, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36067222

RESUMO

When the mixture solution of cyanobacterial proteins, KaiA, KaiB, and KaiC, is incubated with ATP in vitro, the phosphorylation level of KaiC shows stable oscillations with the temperature-compensated circadian period. Elucidating this temperature compensation is essential for understanding the KaiABC circadian clock, but its mechanism has remained a mystery. We analyzed the KaiABC temperature compensation by developing a theoretical model describing the feedback relations among reactions and structural transitions in the KaiC molecule. The model showed that the reduced structural cooperativity should weaken the negative feedback coupling among reactions and structural transitions, which enlarges the oscillation amplitude and period, explaining the observed significant period extension upon single amino-acid residue substitution. We propose that an increase in thermal fluctuations similarly attenuates the reaction-structure feedback, explaining the temperature compensation in the KaiABC clock. The model explained the experimentally observed responses of the oscillation phase to the temperature shift or the ADP-concentration change and suggested that the ATPase reactions in the CI domain of KaiC affect the period depending on how the reaction rates are modulated. The KaiABC clock provides a unique opportunity to analyze how the reaction-structure coupling regulates the system-level synchronized oscillations of molecules.


Assuntos
Relógios Circadianos , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano , Difosfato de Adenosina/metabolismo , Adenosina Trifosfatases/metabolismo , Trifosfato de Adenosina/metabolismo , Proteínas de Bactérias/metabolismo , Relógios Circadianos/fisiologia , Ritmo Circadiano , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/metabolismo , Fosforilação , Temperatura
13.
Compr Physiol ; 12(4): 1-30, 2022 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-36073751

RESUMO

Circadian rhythms are endogenously generated, daily patterns of behavior and physiology that are essential for optimal health and disease prevention. Disruptions to circadian timing are associated with a host of maladies, including metabolic disease and obesity, diabetes, heart disease, cancer, and mental health disturbances. The circadian timing system is hierarchically organized, with a master circadian clock located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus and subordinate clocks throughout the CNS and periphery. The SCN receives light information via a direct retinal pathway, synchronizing the master clock to environmental time. At the cellular level, circadian rhythms are ubiquitous, with rhythms generated by interlocking, autoregulatory transcription-translation feedback loops. At the level of the SCN, tight cellular coupling maintains rhythms even in the absence of environmental input. The SCN, in turn, communicates timing information via the autonomic nervous system and hormonal signaling. This signaling couples individual cellular oscillators at the tissue level in extra-SCN brain loci and the periphery and synchronizes subordinate clocks to external time. In the modern world, circadian disruption is widespread due to limited exposure to sunlight during the day, exposure to artificial light at night, and widespread use of light-emitting electronic devices, likely contributing to an increase in the prevalence, and the progression, of a host of disease states. The present overview focuses on the circadian control of endocrine secretions, the significance of rhythms within key endocrine axes for typical, homeostatic functioning, and implications for health and disease when dysregulated. © 2022 American Physiological Society. Compr Physiol 12: 1-30, 2022.


Assuntos
Transtornos Cronobiológicos , Relógios Circadianos , Doenças Metabólicas , Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Humanos , Núcleo Supraquiasmático/fisiologia
14.
Med Sci (Paris) ; 38(8-9): 669-678, 2022.
Artigo em Francês | MEDLINE | ID: mdl-36094237

RESUMO

The biological clock is a set of evolutionarily conserved "clock proteins" that generate circadian rhythms in behavior and physiological processes. The clock programs these processes at specific times of the day, allowing the organism to optimize its functions by anticipating predictable daily changes such as day/night, hence sleep/wake or feeding/fasting cycles. Modern lifestyle, i.e., exposure to light at night, shift work and irregular eating patterns and sleep schedules desynchronize the clocks residing in each organ. This dissonance is associated with an increased risk of developing various diseases such as cancer, metabolic, cardiovascular and chronic inflammatory diseases.


Title: Récepteurs nucléaires et rythmes circadiens - Implications dans les maladies inflammatoires. Abstract: L'horloge circadienne programme l'ensemble des processus physiologiques, dont l'activité du système immunitaire, à des moments précis de la journée. Elle permet d'optimiser les fonctions de l'organisme en anticipant les changements quotidiens tels que les cycles jour/nuit. Nos habitudes de vie comme l'exposition à la lumière artificielle ou une prise alimentaire irrégulière désynchronisent cependant cette horloge et provoquent des maladies, par exemple inflammatoires. Au niveau moléculaire, elle consiste en un réseau de facteurs de transcription dont certains sont des récepteurs nucléaires, activables par des ligands. Une meilleure compréhension des rythmes biologiques et du rôle des récepteurs nucléaires de l'horloge circadienne permettrait d'ouvrir un champ thérapeutique nouveau. La chronothérapie qui consiste en l'administration d'un composé pharmacologique au moment de la journée le plus propice, permettrait, en ciblant ces récepteurs, d'optimiser l'efficacité du traitement et d'en réduire les possibles effets secondaires.


Assuntos
Relógios Circadianos , Relógios Circadianos/genética , Ritmo Circadiano/genética , Humanos , Receptores Citoplasmáticos e Nucleares , Sono
15.
Proc Natl Acad Sci U S A ; 119(38): e2206348119, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36095195

RESUMO

Shift workers have a 25 to 40% higher risk of depression and anxiety partly due to a misalignment between the central circadian clock and daily environmental/behavioral cycles that may negatively affect mood and emotional well-being. Hence, evidence-based circadian interventions are required to prevent mood vulnerability in shift work settings. We used a stringently controlled 14-d circadian paradigm to assess mood vulnerability during simulated night work with either daytime and nighttime or daytime-only eating as compared with simulated day work (baseline). Simulated night work with daytime and nighttime eating increased depression-like mood levels by 26.2% (p-value adjusted using False Discovery Rates, pFDR = 0.001; effect-size r = 0.78) and anxiety-like mood levels by 16.1% (pFDR = 0.001; effect-size r = 0.47) compared to baseline, whereas this did not occur with simulated night work in the daytime-only eating group. Importantly, a larger degree of internal circadian misalignment was robustly associated with more depression-like (r = 0.77; P = 0.001) and anxiety-like (r = 0.67; P = 0.002) mood levels during simulated night work. These findings offer a proof-of-concept demonstration of an evidence-based meal timing intervention that may prevent mood vulnerability in shift work settings. Future studies are required to establish if changes in meal timing can prevent mood vulnerability in night workers.


Assuntos
Relógios Circadianos , Tolerância ao Trabalho Programado , Afeto , Ritmo Circadiano , Humanos , Refeições
16.
Int J Mol Sci ; 23(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36077345

RESUMO

Human evolution required adaptation to the boundary conditions of Earth, including 1 g gravity. The bipedal mobility of Homo sapiens in that gravitational field causes ground reaction force (GRF) loading of their lower extremities, influencing the integrity of the tissues of those extremities. However, humans usually experience such loading during the day and then a period of relative unloading at night. Many studies have indicated that loading of tissues and cells of the musculoskeletal (MSK) system can inhibit their responses to biological mediators such as cytokines and growth factors. Such findings raise the possibility that humans use such cycles of acute conditioning and deconditioning of the cells and tissues of the MSK system to elaborate critical mediators and responsiveness in parallel with these cycles, particularly involving GRF loading. However, humans also experience circadian rhythms with the levels of a number of mediators influenced by day/night cycles, as well as various levels of biological clocks. Thus, if responsiveness to MSK-generated mediators also occurs during the unloaded part of the daily cycle, that response must be integrated with circadian variations as well. Furthermore, it is also possible that responsiveness to circadian rhythm mediators may be regulated by MSK tissue loading. This review will examine evidence for the above scenario and postulate how interactions could be both regulated and studied, and how extension of the acute cycles biased towards deconditioning could lead to loss of tissue integrity.


Assuntos
Relógios Circadianos , Ritmo Circadiano , Adaptação Fisiológica/fisiologia , Relógios Biológicos , Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Citocinas , Humanos
17.
Int J Mol Sci ; 23(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36077427

RESUMO

BACKGROUND: Circadian rhythm is associated with the aging process and sex differences; however, how age and sex can change circadian regulation systems remains unclear. Thus, we aimed to evaluate age- and sex-related changes in gene expression and identify sex-specific target molecules that can regulate aging. METHODS: Rat livers were categorized into four groups, namely, young male, old male, young female, and old female, and the expression of several genes involved in the regulation of the circadian rhythm was confirmed by in silico and in vitro studies. RESULTS: Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that the expression of genes related to circadian rhythms changed more in males than in females during liver aging. In addition, differentially expressed gene analysis and quantitative real-time polymerase chain reaction/western blotting analysis revealed that Nr1d1 and Nr1d2 expression was upregulated in males during liver aging. Furthermore, the expression of other circadian genes, such as Arntl, Clock, Cry1/2, Per1/2, and Rora/c, decreased in males during liver aging; however, these genes showed various gene expression patterns in females during liver aging. CONCLUSIONS: Age-related elevation of Nr1d1/2 downregulates the expression of other circadian genes in males, but not females, during liver aging. Consequently, age-related upregulation of Nr1d1/2 may play a more crucial role in the change in circadian rhythms in males than in females during liver aging.


Assuntos
Relógios Circadianos , Caracteres Sexuais , Envelhecimento/genética , Animais , Relógios Circadianos/genética , Ritmo Circadiano/genética , Feminino , Fígado , Masculino , Ratos , Fatores de Transcrição
18.
Nutrients ; 14(17)2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36079754

RESUMO

(1) Background: Dietary intake may have a remarkable effect on sleep because skipping breakfast and having a late dinner affects many sleep parameters. Breakfast is the most important meal of the day for children and adults to maintain morning chronotype. We examine whether breakfast style is associated with nutrient intake and sleep factors. (2) Methods: This cross-sectional analysis, with a large sample size of 2671 (766 men and 1805 women aged 20-60 years after data brush-up), was based on data obtained from an online survey. Correlation analysis was performed using Spearman's rank correlation test. The Kruskal-Wallis's test followed by post hoc Dunn's multiple comparison test was used to evaluate the interaction between sleep factors and breakfast categories. Multiple regression analyses were performed to identify variables associated with multiple confounding factors. Dietary data were analyzed using approximately one-month average dietary records from the application. The basic characteristics of the participants (age, sex, and BMI) and other lifestyle-related factors (sleep and physical activity) were obtained accordingly. Sleep parameters including the timing of weekday sleep onset, weekday wake-up, weekend (free day) sleep onset, weekend wake-up, sleep, and midpoints of sleep phase were calculated for each participant. We categorized participants' breakfast types into five groups: (1) Japanese meal, where breakfast may contain Japanese ingredients such as rice; (2) Western meal, where breakfast may contain bread; (3) alternating eating patterns of Japanese and Western meals; (4) cereals and supplements, where breakfast may contain cereals or supplements and energy bars; and (5) skipped breakfast (no breakfast). (3) Results: The midpoint values of the sleep phase on weekends adjusted for sleep debt on work days (MSFsc) related to chronotype were higher in women, suggesting that they may prefer eveningness. Participants with obesity, young age, and low physical activity preferred eveningness with longer sleep durations. Intake of Japanese-style breakfast was significantly associated with early wake-up time on both weekdays and weekends. Cereal-style breakfast intake was significantly associated with late wake-up on both weekdays and weekends. Intake of macronutrients such as protein, fat, carbohydrate, and sodium at breakfast time was positively and strongly associated with the intake of Japanese breakfast, whereas macronutrients were negatively associated with the intake of cereal breakfast. Among micronutrients, vitamin K was positively correlated with Japanese breakfast and negatively correlated with cereal breakfast; (4) Conclusions: Japanese-style breakfast is associated not only with morning preference but also with high intake of macro- and micronutrients.


Assuntos
Desjejum , Ritmo Circadiano , Adulto , Criança , Estudos Transversais , Ingestão de Energia , Comportamento Alimentar , Feminino , Humanos , Japão , Masculino , Micronutrientes , Sono
19.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 1129-1132, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36085837

RESUMO

It is important to detect daily Alzheimer dementia (AD) possibility using unconstrained mattress sensors because dementia takes time before subjective symptoms appear and the main treatment is to slow the rate of progression. Forcusing on circadian rhythm disorder which tend to occur with AD, this paper analyzes the features of unstable circadian rhythms of heart rate associated with its weakening and misalignment in AD. It is found that the external feature of heart rate of AD that of up and down changes seen frequently compared to that of healthy subjects makes the multiple types of effects on the estimation process of the AD detection method based on the circadian instability represented by the trigonometric regression equation estimated from the heart rate. So, we designed two feature values from the effects and analyzed them in an analysis experiment. An analysis experiment was conducted on the heart rate of total 72 days data of one AD patient and total 30 days data of 21 healthy people, and the result confirmed significant differences between the AD and the healthy people at from 0.01% to 0.1 % level for the first feature and at from 0.1% to 5% level for the second feature. And the result shows the possibility that differences in the heart rate features is found between AD and healthy people.


Assuntos
Doença de Alzheimer , Ritmo Circadiano , Doença de Alzheimer/diagnóstico , Leitos , Voluntários Saudáveis , Frequência Cardíaca , Humanos
20.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 152-157, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36085992

RESUMO

In recent years, as a treatment for mental disorders in addition to drug treatment, a non-drug treatment called chronotherapy has been attracting attention. However, the achievement of optimized chronotherapy for each subject's condition requires that the disturbance of the patient's circadian rhythm must be captured over a long duration. Therefore, it is necessary to develop biomarkers that are easy to measure, quantitative, and continuously measured. Complexity analysis of electroencephalograms revealed specific patterns related to circadian rhythms. However, such complexity analysis cannot capture variability in spatial patterns, although moment-to-moment temporal dynamic characteristics can be captured. Therefore, it is necessary to evaluate the dynamic characteristics of the interaction of neural activity throughout the brain. To evaluate the dynamic whole-brain interaction, we proposed a new microstate approach based on the instantaneous frequency distribution. In this context, we hypothesized that it would be possible to detect circadian rhythms using the microstate approach. In this study, to clarify the dynamic interactions of the entire neural network of the brain by circadian rhythms, we measured EEG data at day and night, and detected dynamic state transitions based on the instantaneous frequency distribution of the whole brain from EEG. The results showed the probability of transition among region-specific phase-leading states related to circadian rhythms. This finding might be widely utilized to detect circadian rhythms in healthy and pathological conditions.


Assuntos
Encéfalo , Ritmo Circadiano , Cronoterapia , Eletroencefalografia/métodos , Humanos
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