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1.
Sci Rep ; 14(1): 7760, 2024 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-38565934

RESUMEN

Disrupted or atypical light-dark cycles disrupts synchronization of endogenous circadian clocks to the external environment; extensive circadian rhythm desynchrony promotes adverse health outcomes. Previous studies suggest that disrupted circadian rhythms promote neuroinflammation and neuronal damage post-ischemia in otherwise healthy mice, however, few studies to date have evaluated these health risks with aging. Because most strokes occur in aged individuals, we sought to identify whether, in addition to being a risk factor for poor ischemic outcome, circadian rhythm disruption can increase risk for vascular cognitive impairment and dementia (VCID). We hypothesized that repeated 6 h phase advances (chronic jet lag; CJL) for 8 weeks alters cerebrovascular architecture leading to increased cognitive impairments in aged mice. Female CJL mice displayed impaired spatial processing during a spontaneous alternation task and reduced acquisition during auditory-cued associative learning. Male CJL mice displayed impaired retention of the auditory-cued associative learning task 24 h following acquisition. CJL increased vascular tortuosity in the isocortex, associated with increased risk for vascular disease. These results demonstrate that CJL increased sex-specific cognitive impairments coinciding with structural changes to vasculature in the brain. We highlight that CJL may accelerate aged-related functional decline and could be a crucial target against disease progression.


Asunto(s)
Ritmo Circadiano , Demencia Vascular , Animales , Ratones , Masculino , Femenino , Ritmo Circadiano/fisiología , Fotoperiodo , Reconocimiento en Psicología , Demencia Vascular/etiología , Cognición
2.
Sci Rep ; 14(1): 7778, 2024 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-38565587

RESUMEN

Laboratory animals are typically maintained under 12-h light and 12-h dark (12:12 LD) conditions with a daytime light intensity of ~ 200 lx. In this study, we designed an apparatus that allowed mice to self-select the room light intensity by nose poking. We measured the behavioral rhythms of the mice under this self-controlled light regimen. The mice quickly learned the relationship between their nose pokes and the resulting changes in the light intensity. Under these conditions, the mice exhibited free-running circadian behavior with a period of 24.5 ± 0.4 h. This circadian period was ~ 1 h longer than that of the same strain of mice when they were kept in constant darkness (DD) after 12:12 LD entrainment, and the lengthened period lasted for at least 30 days. The rhythm of the light intensity controlled by the mice also exhibited a similar period, but the phase of the illuminance rhythm preceded the phase of the locomotor activity rhythm. Mice that did not have access to the light controller were also entrained to the illuminance cycle produced by the mice that did have access to the light controller, but with a slightly delayed phase. The rhythm was likely controlled by the canonical circadian clock because mice with tau mutations in the circadian clock gene CSNK1E exhibited short periods of circadian rhythm under the same conditions. These results indicate that the free-running period of mice in the wild may differ from what they exhibit if they are attuned by forced light cycles in laboratories because mice in their natural habitats can self-control their exposure to ambient light, similar to our experimental conditions.


Asunto(s)
Ritmo Circadiano , Actividad Motora , Ratones , Animales , Luz , Fotoperiodo , Oscuridad
3.
Mol Biol Rep ; 51(1): 488, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38578426

RESUMEN

In recent years, mitochondria have gained significant interest in the field of biomedical research due to their impact on human health and ageing. As mitochondrial dynamics are strongly controlled by clock genes, misalignment of the circadian rhythm leads to adverse metabolic health effects. In this review, by exploring various aspects of research and potential links, we hope to update the current understanding of the intricate relationship between DRP1-mediated mitochondrial dynamics and changes in circadian rhythmicity leading to health issues. Thus, this review addresses the potential bidirectional relationships between DRP1-linked mitochondrial function and circadian rhythm misalignment, their impact on different metabolic pathways, and the potential therapeutics for metabolic and systemic disorders.


Asunto(s)
Ritmo Circadiano , Dinaminas , Mitocondrias , Humanos , Ritmo Circadiano/genética , Dinaminas/genética , Dinaminas/metabolismo , Mitocondrias/genética , Mitocondrias/metabolismo
4.
Front Endocrinol (Lausanne) ; 15: 1359772, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38586455

RESUMEN

Meal timing emerges as a crucial factor influencing metabolic health that can be explained by the tight interaction between the endogenous circadian clock and metabolic homeostasis. Mistimed food intake, such as delayed or nighttime consumption, leads to desynchronization of the internal circadian clock and is associated with an increased risk for obesity and associated metabolic disturbances such as type 2 diabetes and cardiovascular diseases. Conversely, meal timing aligned with cellular rhythms can optimize the performance of tissues and organs. In this review, we provide an overview of the metabolic effects of meal timing and discuss the underlying mechanisms. Additionally, we explore factors influencing meal timing, including internal determinants such as chronotype and genetics, as well as external influences like social factors, cultural aspects, and work schedules. This review could contribute to defining meal-timing-based recommendations for public health initiatives and developing guidelines for effective lifestyle modifications targeting the prevention and treatment of obesity and associated metabolic diseases. Furthermore, it sheds light on crucial factors that must be considered in the design of future food timing intervention trials.


Asunto(s)
Relojes Circadianos , Diabetes Mellitus Tipo 2 , Humanos , Ritmo Circadiano , Diabetes Mellitus Tipo 2/complicaciones , Obesidad/etiología , Comidas
5.
Nat Commun ; 15(1): 2834, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38565846

RESUMEN

The circadian clock regulates animal physiological activities. How temperature reorganizes circadian-dependent physiological activities remains elusive. Here, using in-vivo two-photon imaging with the temperature control device, we investigated the response of the Drosophila central circadian circuit to temperature variation and identified that DN1as serves as the most sensitive temperature-sensing neurons. The circadian clock gate DN1a's diurnal temperature response. Trans-synaptic tracing, connectome analysis, and functional imaging data reveal that DN1as bidirectionally targets two circadian neuronal subsets: activity-related E cells and sleep-promoting DN3s. Specifically, behavioral data demonstrate that the DN1a-E cell circuit modulates the evening locomotion peak in response to cold temperature, while the DN1a-DN3 circuit controls the warm temperature-induced nocturnal sleep reduction. Our findings systematically and comprehensively illustrate how the central circadian circuit dynamically integrates temperature and light signals to effectively coordinate wakefulness and sleep at different times of the day, shedding light on the conserved neural mechanisms underlying temperature-regulated circadian physiology in animals.


Asunto(s)
Relojes Circadianos , Proteínas de Drosophila , Animales , Ritmo Circadiano/fisiología , Temperatura , Sueño/fisiología , Drosophila , Relojes Circadianos/fisiología , Proteínas de Drosophila/genética , Drosophila melanogaster/fisiología
6.
Proc Natl Acad Sci U S A ; 121(15): e2321338121, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38568969

RESUMEN

To address the contribution of transcriptional regulation to Drosophila clock gene expression and to behavior, we generated a series of CRISPR-mediated deletions within two regions of the circadian gene timeless (tim), an intronic E-box region and an upstream E-box region that are both recognized by the key transcription factor Clock (Clk) and its heterodimeric partner Cycle. The upstream deletions but not an intronic deletion dramatically impact tim expression in fly heads; the biggest upstream deletion reduces peak RNA levels and tim RNA cycling amplitude to about 15% of normal, and there are similar effects on tim protein (TIM). The cycling amplitude of other clock genes is also strongly reduced, in these cases due to increases in trough levels. These data underscore the important contribution of the upstream E-box enhancer region to tim expression and of TIM to clock gene transcriptional repression in fly heads. Surprisingly, tim expression in clock neurons is only modestly affected by the biggest upstream deletion and is similarly affected by a deletion of the intronic E-box region. This distinction between clock neurons and glia is paralleled by a dramatically enhanced accessibility of the intronic enhancer region within clock neurons. This distinctive feature of tim chromatin was revealed by ATAC-seq (assay for transposase-accessible chromatin with sequencing) assays of purified neurons and glia as well as of fly heads. The enhanced cell type-specific accessibility of the intronic enhancer region explains the resilience of clock neuron tim expression and circadian behavior to deletion of the otherwise more prominent upstream tim E-box region.


Asunto(s)
Proteínas de Drosophila , Drosophila , Animales , Cromatina/metabolismo , Ritmo Circadiano/genética , Proteínas CLOCK/genética , ADN/metabolismo , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Regulación de la Expresión Génica , ARN/metabolismo
7.
J Pineal Res ; 76(3): e12950, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38558122

RESUMEN

Homeobox genes encode transcription factors that are widely known to control developmental processes. This is also the case in the pineal gland, a neuroendocrine brain structure devoted to nighttime synthesis of the hormone melatonin. Thus, in accordance with high prenatal gene expression, knockout studies have identified a specific set of homeobox genes that are essential for development of the pineal gland. However, as a special feature of the pineal gland, homeobox gene expression persists into adulthood, and gene product abundance exhibits 24 h circadian rhythms. Recent lines of evidence show that some homeobox genes even control expression of enzymes catalyzing melatonin synthesis. We here review current knowledge of homeobox genes in the rodent pineal gland and suggest a model for dual functions of homeobox gene-encoded transcription factors in developmental and circadian mature neuroendocrine function.


Asunto(s)
Melatonina , Glándula Pineal , Animales , Glándula Pineal/metabolismo , Genes Homeobox , Melatonina/metabolismo , Roedores/genética , Roedores/metabolismo , Factores de Transcripción/metabolismo , Ritmo Circadiano
8.
FASEB J ; 38(7): e23565, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38558188

RESUMEN

Circadian rhythms in metabolically active tissues are crucial for maintaining physical health. Circadian disturbance (CD) can cause various health issues, such as metabolic abnormalities and immune and cognitive dysfunctions. However, studies on the role of CD in immune cell development and differentiation, as well as the rhythmic expression of the core clock genes and their altered expression under CD, remain unclear. Therefore, we exposed C57bl/6j mice to repeated reversed light-dark cycles for 90 days to research the effects of CD on bone marrow (BM) hematopoietic function. We also researched the effects of CD on endogenous circadian rhythms, temporally dependent expression in peripheral blood and myeloid leukocytes, environmental homeostasis within BM, and circadian oscillations of hematopoietic-extrinsic cues. Our results confirmed that when the light and dark cycles around mice were frequently reversed, the circadian rhythmic expression of the two main circadian rhythm markers, the hypothalamic clock gene, and serum melatonin, was disturbed, indicating that the body was in a state of endogenous CD. Furthermore, CD altered the temporally dependent expression of peripheral blood and BM leukocytes and destroyed environmental homeostasis within the BM as well as circadian oscillations of hematopoietic-extrinsic cues, which may negatively affect BM hematopoiesis in mice. Collectively, these results demonstrate that circadian rhythms are vital for maintaining health and suggest that the association between CD and hematopoietic dysfunction warrants further investigation.


Asunto(s)
Médula Ósea , Relojes Circadianos , Ratones , Animales , Médula Ósea/metabolismo , Fotoperiodo , Ritmo Circadiano/fisiología , Células Madre Hematopoyéticas/metabolismo , Ratones Endogámicos C57BL , Relojes Circadianos/genética
9.
Sci Rep ; 14(1): 8128, 2024 04 07.
Artículo en Inglés | MEDLINE | ID: mdl-38584196

RESUMEN

Fat loss predicts adverse outcomes in advanced heart failure (HF). Disrupted circadian clocks are a primary cause of lipid metabolic issues, but it's unclear if this disruption affects fat expenditure in HF. To address this issue, we investigated the effects of disruption of the BMAL1/REV-ERBα circadian rhythmic loop on adipose tissue metabolism in HF.50 Wistar rats were initially divided into control (n = 10) and model (n = 40) groups. The model rats were induced with HF via monocrotaline (MCT) injections, while the control group received equivalent solvent injections. After establishing the HF model, the model group was further subdivided into four groups: normal rhythm (LD), inverted rhythm (DL), lentivirus vector carrying Bmal1 short hairpin RNA (LV-Bmal1 shRNA), and empty lentivirus vector control (LV-Control shRNA) groups, each with 10 rats. The DL subgroup was exposed to a reversed light-dark cycle of 8 h: 16 h (dark: light), while the rest adhered to normal light-dark conditions (light: dark 12 h: 12 h). Histological analyses were conducted using H&E, Oil Red O, and Picrosirius red stains to examine adipose and liver tissues. Immunohistochemical staining, RT-qPCR, and Western blotting were performed to detect markers of lipolysis, lipogenesis, and beiging of white adipose tissue (WAT), while thermogenesis indicators were detected in brown adipose tissue (BAT). The LD group rats exhibited decreased levels of BMAL1 protein, increased levels of REV-ERBα protein, and disrupted circadian circuits in adipose tissue compared to controls. Additionally, HF rats showed reduced adipose mass and increased ectopic lipid deposition, along with smaller adipocytes containing lower lipid content and fibrotic adipose tissue. In the LD group WAT, expression of ATGL, HSL, PKA, and p-PKA proteins increased, alongside elevated mRNA levels of lipase genes (Hsl, Atgl, Peripilin) and FFA ß-oxidation genes (Cpt1, acyl-CoA). Conversely, lipogenic gene expression (Scd1, Fas, Mgat, Dgat2) decreased, while beige adipocyte markers (Cd137, Tbx-1, Ucp-1, Zic-1) and UCP-1 protein expression increased. In BAT, HF rats exhibited elevated levels of PKA, p-PKA, and UCP-1 proteins, along with increased expression of thermogenic genes (Ucp-1, Pparγ, Pgc-1α) and lipid transportation genes (Cd36, Fatp-1, Cpt-1). Plasma NT-proBNP levels were higher in LD rats, accompanied by elevated NE and IL-6 levels in adipose tissue. Remarkably, morphologically, the adipocytes in the DL and LV-Bmal1 shRNA groups showed reduced size and lower lipid content, while lipid deposition in the liver was more pronounced in these groups compared to the LD group. At the gene/protein level, the BMAL1/REV-ERBα circadian loop exhibited severe disruption in LV-Bmal1 shRNA rats compared to LD rats. Additionally, there was increased expression of lipase genes, FFA ß oxidation genes, and beige adipocyte markers in WAT, as well as higher expression of thermogenic genes and lipid transportation genes in BAT. Furthermore, plasma NT-proBNP levels and adipose tissue levels of NE and IL-6 were elevated in LV-Bmal1 shRNA rats compared with LD rats. The present study demonstrates that disruption of the BMAL1/REV-ERBα circadian rhythmic loop is associated with fat expenditure in HF. This result suggests that restoring circadian rhythms in adipose tissue may help counteract disorders of adipose metabolism and reduce fat loss in HF.


Asunto(s)
Factores de Transcripción ARNTL , Insuficiencia Cardíaca , Ratas , Animales , Factores de Transcripción ARNTL/genética , Factores de Transcripción ARNTL/metabolismo , Monocrotalina , Gastos en Salud , Interleucina-6/metabolismo , Ratas Wistar , Ritmo Circadiano/genética , Tejido Adiposo Pardo/metabolismo , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/metabolismo , Lipasa/metabolismo , ARN Interferente Pequeño/metabolismo , Lípidos
10.
Front Neural Circuits ; 18: 1385908, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38590628

RESUMEN

Animals need sleep, and the suprachiasmatic nucleus, the center of the circadian rhythm, plays an important role in determining the timing of sleep. The main input to the suprachiasmatic nucleus is the retinohypothalamic tract, with additional inputs from the intergeniculate leaflet pathway, the serotonergic afferent from the raphe, and other hypothalamic regions. Within the suprachiasmatic nucleus, two of the major subtypes are vasoactive intestinal polypeptide (VIP)-positive neurons and arginine-vasopressin (AVP)-positive neurons. VIP neurons are important for light entrainment and synchronization of suprachiasmatic nucleus neurons, whereas AVP neurons are important for circadian period determination. Output targets of the suprachiasmatic nucleus include the hypothalamus (subparaventricular zone, paraventricular hypothalamic nucleus, preoptic area, and medial hypothalamus), the thalamus (paraventricular thalamic nuclei), and lateral septum. The suprachiasmatic nucleus also sends information through several brain regions to the pineal gland. The olfactory bulb is thought to be able to generate a circadian rhythm without the suprachiasmatic nucleus. Some reports indicate that circadian rhythms of the olfactory bulb and olfactory cortex exist in the absence of the suprachiasmatic nucleus, but another report claims the influence of the suprachiasmatic nucleus. The regulation of circadian rhythms by sensory inputs other than light stimuli, including olfaction, has not been well studied and further progress is expected.


Asunto(s)
Hipotálamo , Núcleo Supraquiasmático , Animales , Núcleo Supraquiasmático/metabolismo , Hipotálamo/metabolismo , Ritmo Circadiano/fisiología , Péptido Intestinal Vasoactivo/metabolismo , Sueño , Arginina Vasopresina/metabolismo
11.
Front Endocrinol (Lausanne) ; 15: 1294638, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38590820

RESUMEN

As the incidence of type 2 diabetes mellitus (T2DM) is increasing rapidly and its consequences are severe, effective intervention and prevention, including sleep-related interventions, are urgently needed. As a component of sleep architecture, naps, alone or in combination with nocturnal sleep, may influence the onset and progression of T2DM. Overall, napping is associated with an increased risk of T2DM in women, especially in postmenopausal White women. Our study showed that napping >30 minutes (min) increased the risk of T2DM by 8-21%. In addition, non-optimal nighttime sleep increases T2DM risk, and this effect combines with the effect of napping. For nondiabetic patients, napping >30 min could increase the risks of high HbA1c levels and impaired fasting glucose (IFG), which would increase the risk of developing T2DM later on. For diabetic patients, prolonged napping may further impair glycemic control and increase the risk of developing diabetic complications (e.g., diabetic nephropathy) in the distant future. The following three mechanisms are suggested as interpretations for the association between napping and T2DM. First, napping >30 min increases the levels of important inflammatory factors, including interleukin 6 and C-reactive protein, elevating the risks of inflammation, associated adiposity and T2DM. Second, the interaction between postmenopausal hormonal changes and napping further increases insulin resistance. Third, prolonged napping may also affect melatonin secretion by interfering with nighttime sleep, leading to circadian rhythm disruption and further increasing the risk of T2DM. This review summarizes the existing evidence on the effect of napping on T2DM and provides detailed information for future T2DM intervention and prevention strategies that address napping.


Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Humanos , Femenino , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/epidemiología , Sueño , Ritmo Circadiano , Inflamación
13.
Curr Biol ; 34(7): R284-R286, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38593773

RESUMEN

While the daily rhythmicity of organisms is entrained by several cues, light is thought to be the strongest signal. Surprisingly, a new study in a moth shows that olfactory communication can be even more powerful for synchronization, and, at least to some extent, works across related species.


Asunto(s)
Ritmo Circadiano , Olfato
14.
Sci Rep ; 14(1): 8354, 2024 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594272

RESUMEN

Sleep and circadian rhythm disorders are very common in adolescents and have been linked to suicidal ideation. However, little is known about adolescent sleep before a suicide attempt (SA). The objectives of this study were to compare the sleep of adolescents aged 13 to 18 over a period of 4 weeks before a SA compared to a non-SA group, then to analyze the association between sleep, support social and well-being based on information from validated questionnaires. In 2015, 250 adolescents were included, 55 were recruited the day after a SA in French hospitals (before SA evaluations were retrospective). Logistic regression analyzes showed that during school days, bedtime was equivalent in both groups, but sleep onset latency was significantly longer in SA (86 min vs. 52 min, p = 0.016), and wake-up time was earlier (6 h 22 vs. 6 h 47, p = 0.002), resulting in a shorter total sleep time of 44 min (OR = 0.76, CI 95% [0.61-0.93]) the month preceding SA. Adolescents with longer sleep time performed better on perceived psychological well-being (p = 0.005), relationship with parents (p = 0.011) and school environment (p < 0.001). Results indicate a significant change in the quantity and quality of adolescents' subjective sleep in the 4 weeks preceding SA requiring objective measures to study the predictive properties of sleep in SA.


Asunto(s)
Sueño , Intento de Suicidio , Humanos , Adolescente , Intento de Suicidio/psicología , Estudios Retrospectivos , Ideación Suicida , Ritmo Circadiano , Factores de Riesgo
15.
Methods Mol Biol ; 2795: 43-53, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38594526

RESUMEN

The pace of circadian rhythms remains relatively unchanged across a physiologically relevant range of temperatures, a phenomenon known as temperature compensation. Temperature compensation is a defining characteristic of circadian rhythms, ensuring that clock-regulated processes occur at approximately the same time of day across a wide range of conditions. Despite the identification of several genes involved in the regulation of temperature compensation, the molecular mechanisms underlying this process are still not well understood. High-throughput assays of circadian period are essential for the investigation of temperature compensation. In this chapter, we present a luciferase imaging-based method that enables robust and accurate examination of temperature compensation in the plant circadian clock.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Relojes Circadianos , Temperatura , Relojes Circadianos/genética , Arabidopsis/genética , Ritmo Circadiano/genética , Luciferasas/genética , Proteínas de Arabidopsis/genética
16.
Methods Mol Biol ; 2795: 123-134, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38594534

RESUMEN

Phase separation is an important mechanism for regulating various cellular functions. The EARLY FLOWERING 3 (ELF3) protein, an essential element of the EVENING COMPLEX (EC) involved in circadian clock regulation, has been shown to undergo phase separation. ELF3 is known to significantly influence elongation growth and flowering time regulation, and this is postulated to be due to whether the protein is in the dilute or phase-separated state. Here, we present a brief overview of methods for analyzing ELF3 phase separation in vitro, including the generation of phase diagrams as a function of pH and salt versus protein concentrations, optical microscopy, fluorescence recovery after photobleaching (FRAP), and turbidity assays.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Relojes Circadianos , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Factores de Transcripción/metabolismo , Mutación , Luz , Relojes Circadianos/fisiología , Regulación de la Expresión Génica de las Plantas , Ritmo Circadiano/fisiología
17.
Methods Mol Biol ; 2795: 213-225, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38594541

RESUMEN

Understanding gene expression dynamics in the context of the time of day and temperature response is an important part of understanding plant thermotolerance in a changing climate. Performing "gating" experiments under constant conditions and light-dark cycles allows users to identify and dissect the contribution of the time of day and circadian clock to the dynamic nature of stress-responsive genes. Here, we describe the design of specific laboratory experiments in plants (Arabidopsis thaliana and bread wheat, Triticum aestivum) to investigate temporal responses to heat (1 h at 37 °C) or cold (3 h at 4 °C), and we include known marker genes that have circadian-gated responses to temperature changes.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Relojes Circadianos , Temperatura , Factores de Transcripción/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Relojes Circadianos/genética , Ritmo Circadiano/genética , Regulación de la Expresión Génica de las Plantas
18.
Artículo en Alemán | MEDLINE | ID: mdl-38472403

RESUMEN

Changes in sleep are reported in adolescents with depression with a frequency of up to 71%. Aspects of chronobiology and sleep based on the current scientific literature are illustrated and summarized in this narrative review. The circadian clock synchronizes organisms to the light-dark structure of the environment. The individual synchronization is called "chronotype." Chronotype changes according to age, among other factors, and adolescents experience the latest chronotypes overall. The potential discrepancy between internal and external time is called "social jetlag." Social jetlag is especially pronounced during adolescence. It is associated with numerous health risks, such as depression. Changes in sleep behavior in affective disorders and its comorbidity to depression have also been well described in the literature. In this article, underlying concepts from chronobiology and sleep medicine are initially summarized. Then, health risks of disrupted sleep-wake behavior are described, and connections to depression specifically during adolescence are drawn. The article concludes with clinical recommendations for sleep disorders and depression during adolescence as well as suggestions for further research.


Asunto(s)
Ritmo Circadiano , Depresión , Humanos , Adolescente , Depresión/epidemiología , Depresión/terapia , Encuestas y Cuestionarios , Alemania , Sueño
19.
Biochem Biophys Res Commun ; 708: 149813, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38522403

RESUMEN

The chemotherapeutic agent tegafur, a prodrug that prolongs the half-life of fluorouracil (5-FU), exerts antitumor effects against various cancers. Since tegafur is metabolized to 5-FU by CYP2A6 in the liver, the expression of CYP2A6 determines the effect of tegafur. Here, we report that the expression rhythm of Cyp2a5, a homolog of human CYP2A6, in female mice causes dosing time-dependent differences in tegafur metabolism. In the livers of female mice, CYP2A5 expression showed a circadian rhythm, peaking during the dark period. This rhythm is regulated by RORA, a core clock component, and abrogation of the CYP2A5 activity abolished the time-dependent difference in the rate of tegafur metabolism in female mice. Furthermore, administration of tegafur to mice transplanted with 4T1 breast cancer cells during the dark period suppressed increases in tumor size compared to female mice treated during the light period. Our findings reveal a novel relationship between 5-FU prodrugs and circadian clock machinery, potentially influencing antitumor effects, and contributing to the development of time-aware chemotherapy regimens for breast cancer.


Asunto(s)
Hidrocarburo de Aril Hidroxilasas , Neoplasias de la Mama , Femenino , Humanos , Animales , Ratones , Tegafur/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Fluorouracilo/farmacología , Fluorouracilo/metabolismo , Ritmo Circadiano
20.
Int Arch Occup Environ Health ; 97(4): 461-471, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38429581

RESUMEN

PURPOSE: Whether chronotype affects the health outcomes of night shift work populations is unknown. This study aimed to assess the influence of different chronotypes in the rotating night shift population on sleep status, mood, blood pressure (BP), and heart rate variability (HRV), as well as the circadian rhythm of BP and HRV. METHODS: A total of 208 rotating night shift workers were included. All participants completed structured questionnaires to assess chronotype, mood and sleep status. During their daily lives outside of the night shift, they underwent 24-hour Holter electrocardiogram monitoring and 24-hour ambulatory blood pressure monitoring. Day-time and night-time BP and BP dipping were obtained. Day-time and night-time HRV values (SDNN, RMSSD, LF, HF, LF nu, SD1, SD2 and SD2/SD1) were calculated and fitted to the cosine period curve. Three circandian parameters (mesor, amplitude and acrophase) were extracted to quantify the circadian rhythm of the HRV indices. RESULTS: Among all three groups, E-type showed more fatigue and sleepiness. In addition, E-type showed blunted diastolic BP dipping. Notably, E-type showed association with higher RMSSD, LF, HF and SD1 in the night time, and higher mesors of RMSSD and LF and amplitude of SD2/SD1 in circadian analysis. CONCLUSION: Chronotype is a factor affecting fatigue, sleepiness and cardiovascular circadian rhythms of rotating night shift workers. Chronotype should be taken into consideration for managing night-shift rotation to promote occupational health.


Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial , Cronotipo , Sindactilia , Humanos , Somnolencia , Sueño/fisiología , Ritmo Circadiano/fisiología , Fatiga , Tolerancia al Trabajo Programado/fisiología
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