Chronobiology

时间生物学
  • 文章类型: Journal Article
    睡眠和生物节律是整个生命周期中情绪调节不可或缺的一部分,特别是在双相情感障碍(BD),睡眠阶段的改变,结构,和持续时间发生在所有的情绪状态。这些中断与生活质量下降有关,自杀风险增加,认知功能受损,和增加复发率。这篇综述重点介绍了BD中睡眠障碍的病理生理学,旨在巩固对这些现象的理解和临床应用。它还总结了睡眠和生物节律评估方法的演变,包括生态瞬时评估(EMA)和数字表型。它强调了认识到昼夜节律参与情绪调节的重要性,提示潜在的治疗靶点。未来的研究方向包括阐明生物钟基因机制,了解环境对昼夜节律的影响,并研究BD患者睡眠障碍与情绪调节之间的双向关系。标准化评估方法并解决与EMA技术和数字表型相关的隐私问题对于推进研究至关重要。协作努力对于增强临床适用性和理解生物节律在BD诊断和治疗中的更广泛意义至关重要。总的来说,认识到睡眠和生物节律在BD中的重要性,通过有针对性的干预措施和更深入地了解疾病的潜在机制,有望改善预后.
    Sleep and biological rhythms are integral to mood regulation across the lifespan, particularly in bipolar disorder (BD), where alterations in sleep phase, structure, and duration occur in all mood states. These disruptions are linked to poorer quality of life, heightened suicide risk, impaired cognitive function, and increased relapse rates. This review highlights the pathophysiology of sleep disturbances in BD and aims to consolidate understanding and clinical applications of these phenomena. It also summarizes the evolution of sleep and biological rhythms assessment methods, including ecological momentary assessment (EMA) and digital phenotyping. It underscores the importance of recognizing circadian rhythm involvement in mood regulation, suggesting potential therapeutic targets. Future research directions include elucidating circadian clock gene mechanisms, understanding environmental impacts on circadian rhythms, and investigating the bidirectional relationship between sleep disturbances and mood regulation in BD. Standardizing assessment methods and addressing privacy concerns related to EMA technology and digital phenotyping are essential for advancing research. Collaborative efforts are crucial for enhancing clinical applicability and understanding the broader implications of biological rhythms in BD diagnosis and treatment. Overall, recognizing the significance of sleep and biological rhythms in BD offers promise for improved outcomes through targeted interventions and a deeper understanding of the disorder\'s underlying mechanisms.
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  • 文章类型: Journal Article
    背景:评估青少年时间型与饮食紊乱之间关系的证据很少。当前的研究试图评估西班牙青少年样本中时间型与饮食失调之间的关系。
    方法:这项二级横断面研究分析了饮食健康和日常生活活动(EHDLA)研究的数据。样本包括来自ValledeRicote(穆尔西亚地区,西班牙)。使用儿童晨氏/平均度量表(MESC)评估时序型。两位心理学家使用《病态》对饮食失调进行了评估,Control,一,胖,和食品(SCOFF)问卷。
    结果:与早显型(M=0.7;95%CI0.5至0.8)(p=0.010)相比,具有晚显型的青少年SCOFF得分更高(估计边际均值[M]=1.1;95%置信区间[CI]0.7至1.5),以及具有中间时间型的那些(M=0.6;95%CI0.5至0.8)(p=0.032)。在具有晚上时间型的青少年中,发现饮食紊乱的预测概率更高(39.5%;95%CI22.8%至59.1%),与中间型的青少年(14.9%;95%CI10.8%~20.1%)(p=0.008)和早型型的青少年(16.9%;95%CI11.6%~24.0%)(p=0.021)相比.
    结论:这项研究表明,与早熟或中间型的青少年相比,具有晚熟型的青少年更有可能表现出饮食行为紊乱。这些发现强调了在青少年健康中考虑时间型的重要性,特别是在制定有针对性的干预措施,以防止饮食失调。
    BACKGROUND: Evidence assessing the relationship between chronotype and disordered eating in adolescents is scarce. The current study tried to evaluate the association between chronotype and disordered eating in a sample of Spanish adolescents.
    METHODS: This secondary cross-sectional study analyzed data from the Eating Healthy and Daily Life Activities (EHDLA) study. The sample consisted of 703 adolescents (56.3% girls) aged between 12 and 17 years from the Valle de Ricote (Region of Murcia, Spain). Chronotype was assessed using the Morningness/Eveningness Scale in Children (MESC). Disordered eating was evaluated by two psychologists using the Sick, Control, One, Fat, and Food (SCOFF) questionnaire.
    RESULTS: Adolescents with an eveningness chronotype showed a higher SCOFF score (estimated marginal mean [M] = 1.1; 95% confidence interval [CI] 0.7 to 1.5) in comparison with adolescents with a morningness chronotype (M = 0.7; 95% CI 0.5 to 0.8) (p = 0.010), as well as with those with an intermediate chronotype (M = 0.6; 95% CI 0.5 to 0.8) (p = 0.032). A higher predictive probability of having disordered eating was identified in adolescents with an eveningness chronotype (39.5%; 95% CI 22.8% to 59.1%), compared to adolescents with an intermediate chronotype (14.9%; 95% CI 10.8% to 20.1%) (p = 0.008) and with their counterparts with a morningness chronotype (16.9%; 95% CI 11.6% to 24.0%) (p = 0.021).
    CONCLUSIONS: This study reveals that adolescents with an eveningness chronotype are more likely to exhibit disordered eating behaviors compared to those with morningness or intermediate chronotypes. These findings highlight the importance of considering chronotype in adolescent health, particularly in developing targeted interventions to prevent eating disorders.
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  • 文章类型: Journal Article
    背景:众所周知,马里是血吸虫病流行的国家,清洁水的供应有限。这迫使许多社区依靠开放的淡水体进行许多人水接触(HWC)活动。然而,与这些水系统的接触与血吸虫感染水平之间的关系目前受到的关注有限。这项研究评估了人与水的相互作用,包括在马里Kayes地区的两个社区中,cer虫的出现方式及其对尿血吸虫病传播的影响。
    方法:我们于2021年9月首先对儿童进行了寄生虫学研究,然后对人口中人与水接触活动的定量观察进行了横断面研究,最后是2022年9月在接触点对蜗牛传染性的研究。这项研究在两个社区进行,马里西部Kayes地区的FangounéBamanan和Diakalèl。时间生物学研究的重点是从自然感染的蜗牛中释放子囊。通过靶向cox1区域对释放的尾c进行分子基因分型,以及DNA的ITS和18S核糖体DNA基因(18SrDNA)区域。社会人口统计学参数之间的联系,使用多变量统计分析或逻辑回归模型建立人体水接触点和血尿。
    结果:导致97名参与者接触水的主要因素是家庭活动(62.9%)。在14个采样点收集的378只蜗牛中,27(7.1%)排泄血吸虫尾蚴,FangounéBamanan的15.0%(19/126)和Diakalel的3.3%(8/252)。在FangouneéBamanan中,血吸虫尾蚴的释放显示出三种不同的模式:(i)早期释放高峰(6:00-8:00AM),(ii)中午释放高峰(上午10:00-下午12:00)和(iii)双重高峰:(上午6:00-8:00)和(下午6:00-8:00)尾c释放;Diakalel中的两种释放模式:提前释放(上午6:00-8:00)和(ii)中午释放(下午12:00-2:00)。在昼夜早期(6:00-8:00AM)或夜间发射模式(6:00-8:00PM)释放的所有尾蚴都是杂种寄生虫,具有与ITS和18SrDNA相关的cox1牛S.bovis或curassoni。或中午模式(上午8:00-下午6:00)是纯的嗜血杆菌。
    结论:我们的研究表明,家庭活动是Kayes地区暴露的主要来源。在Diakalel和FangunéBamanan分别观察到两种和三种尾c发射模式。这些结果表明,寄生虫适应人水接触期,以增加其传染性。
    BACKGROUND: Mali is known to be a schistosomiasis-endemic country with a limited supply of clean water. This has forced many communities to rely on open freshwater bodies for many human-water contact (HWC) activities. However, the relationship between contact with these water systems and the level of schistosome infection is currently receiving limited attention. This study assessed human-water interactions including cercarial emergence pattern and their influences on urinary schistosomiasis transmission in two communities in the Kayes district of Mali.
    METHODS: We carried out a parasitological study first in children in September 2021, then a cross-sectional study of quantitative observations of human-water contact activities in the population, and finally a study of snail infectivity at contact points in September 2022. The study took place in two communities, Fangouné Bamanan and Diakalèl in the Kayes region of western Mali. The chronobiological study focused on cercarial release from naturally infected snails. Released cercariae were molecularly genotyped by targeting the cox1 region, and the ITS and 18S ribosmal DNA gene (18S rDNA) regions of the DNA. Links between sociodemographic parameters, human water-contact points and hematuria were established using multivariate statistical analysis or the logistic regression model.
    RESULTS: The main factor predisposing the 97 participants to water contact was domestic activity (62.9%). Of the 378 snails collected at 14 sampling sites, 27 (7.1%) excreted schistosome cercariae, with 15.0% (19/126) at Fangouné Bamanan and 3.3% (8/252) at Diakalel. The release of Schistosoma cercariae shows three different patterns in Fangouné Bamanan: (i) an early release peak (6:00-8:00 AM), (ii) a mid-day release peak (10:00 AM-12:00 PM) and (iii) a double peak: (6:00-8:00 AM) and (6:00-8:00 PM) cercariae release; and two release patterns in Diakalel: early release (6:00-8:00 AM) and (ii) mid-day release (12:00-2:00 PM). All cercariae released during early diurnal (6:00-8:00 AM) or nocturnal emission patterns (6:00-8:00 PM) were hybrids parasite having an cox1 S. bovis or S. curassoni associated with an ITS and 18S rDNA of S. haematobium while the cercariae released during diurnal, or mid-day patterns (8:00 AM-6:00 PM) were pure S. haematobium.
    CONCLUSIONS: Our study showed that domestic activity is the main source of exposure in the Kayes region. Two and three cercariae emission patterns were observed at Diakalel and Fangouné Bamanan respectively. These results suggest that the parasite adapts to the human-water contact period in order to increase its infectivity.
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  • 文章类型: Journal Article
    时间生态位划分是物种形成的一个被低估的驱动因素。虽然昆虫长期以来一直是昼夜节律生物学的模型,允许diel-niches适应性变化的基因和电路仍然知之甚少。我们比较了密切相关的日间和夜间活跃的非模型野生蚕蛾的基因表达,与其他类似的生态。使用基于直系同源的管道比较两种蛾物种的RNA-Seq模式,我们发现超过25对基因直系同源物显示差异表达。值得注意的是,基因迪斯科舞厅,参与昼夜节律控制,果蝇的视神经叶和时钟神经元发育,显示蛾头中成年昼夜节律mRNA的强烈循环。Disco在蛾中高度保守,并且具有额外的锌指结构域,具有特定的夜间和昼夜突变。我们建议迪斯科舞厅作为飞蛾中时间diel生态位多样化的候选基因。
    Temporal ecological niche partitioning is an underappreciated driver of speciation. While insects have long been models for circadian biology, the genes and circuits that allow adaptive changes in diel-niches remain poorly understood. We compared gene expression in closely related day- and night-active non-model wild silk moths, with otherwise similar ecologies. Using an ortholog-based pipeline to compare RNA-Seq patterns across two moth species, we find over 25 pairs of gene orthologs showing differential expression. Notably, the gene disco, involved in circadian control, optic lobe and clock neuron development in Drosophila, shows robust adult circadian mRNA cycling in moth heads. Disco is highly conserved in moths and has additional zinc-finger domains with specific nocturnal and diurnal mutations. We propose disco as a candidate gene for the diversification of temporal diel-niche in moths.
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  • 文章类型: Journal Article
    虽然时间生物学作为一门科学学科的形式化发生在20世纪中叶,对节奏现象的探索有着更长的历史,1729年,DeMairan在黑暗中观察到含羞草。在这个历史叙事中,查尔斯·达尔文以研究植物的“睡眠运动”而闻名。然而,达尔文探索生物节律的完整范围仍未被完全理解。通过对达尔文著作的详细考察,细致的观察,实验,和概念化,我们揭示了超过他在植物方面广受认可的工作的深度,揭示了对生物节律的更广泛的兴趣和洞察力比传统公认的。
    While the formalization of chronobiology as a scientific discipline occurred in the mid-20th century, the exploration of rhythmic phenomena has a longer history, notably exemplified by De Mairan\'s observations of Mimosa pudica in darkness in 1729. In this historical narrative, Charles Darwin is known for his investigations into the \"sleep movements\" of plants. Nevertheless, the complete scope of Darwin\'s exploration of biological rhythms remains incompletely understood. Through a detailed examination of Darwin\'s writings, meticulous observations, experiments, and conceptualizations, we unveil a depth of engagement that surpasses his widely acknowledged work on plants, revealing a more extensive interest in and insight into biological rhythms than traditionally recognized.
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  • 文章类型: Journal Article
    Takotsubo综合征(TTS)的发病可能表现出特定的时间生物学模式,其特征是根据一天中的时间而变化,星期几,一年中的月份。这项研究的目的是充分探索时间模式(昼夜节律,每周和季节性)在TTS发作时。对文献进行了系统回顾和荟萃分析,以研究(2006-2024年)报告时间模式(昼夜节律,每周和/或季节性)在TTS发作时。在检索到的4257项研究中,20名(包括64,567名受试者)符合所有资格标准。数据汇总使用随机效应模型作为合并风险比和归因风险(AR)。比例分析(包括8项研究;n=853)显示,从早晨到晚上的TTS合并率呈下降趋势(合并TTS率:34.0%;32.1%;21.7%;早上12.7%,下午,晚上和晚上,分别)。观察到相同的模式,按先前应激因素或事件的类型分层,考虑到身体压力源(早晚汇总率:37.6%和9.8%,分别),并且在没有事件可以被识别的情况下。TTS发作的汇总率在周一和周二达到峰值(分别为17.3%和18.4%),然后在一周内下降,周五和周六达到最低利率(10.6%和10.8%,分别),没有性别差异。TTS发病在夏季达到最高值,冬季最低(27.9%,夏季和冬季为21.7%,分别)。基于TTS晨峰的分析(占所有注册事件的33%)的RR为1.46(95%CI:1.38-1.54),以一周为基础,RR为1.26(1.16-1.35),基于季节的RR为1.04(1.04-1.05)。TTS发病表现出特定的时间生物学模式,以早上的高峰为特征,周一和周二。与其他心血管紧急情况不同,夏季TTS更为频繁。需要进一步的研究来充分了解潜在的病理生理机制,以便制定相关的管理和预防策略。
    Takotsubo syndrome (TTS) might exhibit particular chronobiological patterns in its onset, characterized by variations according to time of the day, day of the week, and month of the year. The aim of this study was to fully explore the temporal patterns (circadian, weekly and seasonal) in the onset of TTS. A systematic review and meta-analysis of literature were conducted for studies (2006-2024) reporting the temporal patterns (circadian, weekly and/or seasonal) in the onset of TTS. Among the 4257 studies retrieved, 20 (including 64,567 subjects) fulfilled all eligibility criteria. Data were aggregated used random effects model as pooled risk ratio and the attributable risk (AR). The proportion analysis (including 8 studies; n=853) showed a decreasing pattern of the pooled rates of TTS shifting from the morning to the night (pooled TTS rates: 34.0%; 32.1%; 21.7%; 12.7% in the morning, afternoon, evening and night, respectively). The same pattern was observed stratifying by type of preceding stressful factor or event, considering physical stressors (pooled rates in the morning and night: 37.6% and 9.8%, respectively), and also in case no event could be identified. The pooled rates of TTS onset peaked on Monday and Tuesday (17.3% and 18.4% respectively), then declined during the week, reaching the lowest rates on Friday and Saturday (10.6% and 10.8%, respectively), with no sex differences. TTS onset reached the highest values on summer, and the lowest in winter (27.9% versus 21.7% in summer and winter, respectively). The TTS morning peak based analyses (∼33% of all the registered events) account for a RR of 1.46 (95% CI: 1.38-1.54), the week-based for a RR of 1.26 (1.16-1.35), the season-based for a RR of 1.04 (1.04-1.05). TTS onset exhibits specific chronobiological patterns, characterized by a peak during the morning hours, and on Monday and Tuesday. Differing from other cardiovascular emergencies TTS was more frequent during summer. Further studies are needed to fully understand the underlying pathophysiological mechanisms in order to tailor relative management and preventive strategies.
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  • 文章类型: Journal Article
    越来越多的数据表明,骨骼肌收缩功能和葡萄糖代谢随时间的变化而变化。提出了对内在骨骼肌特性的时间生物学效应作为潜在的介体。然而,没有研究直接调查24小时昼夜节律周期内骨骼肌的内在收缩功能或葡萄糖代谢。为了解决这个问题,我们评估了内在的收缩功能和耐力,以及收缩刺激的葡萄糖摄取,在一天中的四个时间(zeitgeber时间1、7、13、19)来自小鼠的孤立的趾长伸肌和比目鱼。重要的是,尽管这两个肌肉在基因表达中都表现出昼夜节律相关的变化,内在收缩功能的四个时间点之间没有差异,耐力,和收缩刺激的葡萄糖摄取,不管性别。总的来说,这些结果表明,运动表现的一天中时间变化和运动的降糖益处不是由于对内在肌肉功能或收缩刺激的葡萄糖摄取的时间生物学效应.
    A growing body of data suggests that skeletal muscle contractile function and glucose metabolism vary by time-of-day, with chronobiological effects on intrinsic skeletal muscle properties being proposed as the underlying mediator. However, no studies have directly investigated intrinsic contractile function or glucose metabolism in skeletal muscle over a 24 h circadian cycle. To address this, we assessed intrinsic contractile function and endurance, as well as contraction-stimulated glucose uptake, in isolated extensor digitorum longus and soleus from mice at four times-of-day (zeitgeber times 1, 7, 13, 19). Significantly, though both muscles demonstrated circadian-related changes in gene expression, there were no differences between the four time points in intrinsic contractile function, endurance, and contraction-stimulated glucose uptake, regardless of sex. Overall, these results suggest that time-of-day variation in exercise performance and the glycemia-reducing benefits of exercise are not due to chronobiological effects on intrinsic muscle function or contraction-stimulated glucose uptake.
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  • 文章类型: Journal Article
    背景:时间生物学是专注于研究生物过程中周期性的科学领域。在哺乳动物中,大多数生理变量表现出昼夜节律,比如新陈代谢,体温,运动活动,和睡眠。可以通过检查时间序列并提取与振荡周期相关的参数来统计评估生物节律性,它的振幅,相位位移,和整体可变性。
    方法:我们开发了一个名为CircadiPy的库,它封装了时间生物学分析和数据检查的方法,作为分析和解释时间生物学数据的开放获取工具包。包装设计灵活,全面和可扩展,以协助研究处理受节奏影响或影响的过程。
    结果:结果显示该工具包能够指导用户分析从各种记录来源收集的时间生物学数据,同时还提供与昼夜节律相关的精确参数。
    方法:该建议库的分析方法提供了以直接且无成本的方式检查和获取时间生物学参数的机会,与商业工具相比。
    结论:此外,作为一个开源工具,它使社区有机会为新功能做出贡献,分析方法,和图形可视化给出了时间序列数据分析的简化计算方法,在单个Python对象中使用简单而全面的管道。
    BACKGROUND: Chronobiology is the scientific field focused on studying periodicity in biological processes. In mammals, most physiological variables exhibit circadian rhythmicity, such as metabolism, body temperature, locomotor activity, and sleep. The biological rhythmicity can be statistically evaluated by examining the time series and extracting parameters that correlate to the period of oscillation, its amplitude, phase displacement, and overall variability.
    METHODS: We have developed a library called CircadiPy, which encapsulates methods for chronobiological analysis and data inspection, serving as an open-access toolkit for the analysis and interpretation of chronobiological data. The package was designed to be flexible, comprehensive and scalable in order to assist research dealing with processes affected or influenced by rhythmicity.
    RESULTS: The results demonstrate the toolkit\'s capability to guide users in analyzing chronobiological data collected from various recording sources, while also providing precise parameters related to the circadian rhythmicity.
    METHODS: The analysis methodology from this proposed library offers an opportunity to inspect and obtain chronobiological parameters in a straightforward and cost-free manner, in contrast to commercial tools.
    CONCLUSIONS: Moreover, being an open-source tool, it empowers the community with the opportunity to contribute with new functions, analysis methods, and graphical visualizations given the simplified computational method of time series data analysis using an easy and comprehensive pipeline within a single Python object.
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  • 文章类型: Journal Article
    亮/暗周期是同步人类生物钟的主要外部线索。现代生活方式通常导致较少的日光暴露和24小时振幅减弱。我们评估了室外日光暴露的关联(频率,持续时间,规律性和移位)具有按睡眠阶段估计的时间类型,常规的规律性,睡眠,幸福(WHO-5),和抑郁症状(PHQ-9),在2020年7月至11月在线调查的1,095名参与者(81.8%为女性;87.9%为18-49岁)中。我们分析了日光-情绪关系与时间型估计的直接和间接关联,常规规律性,作为调解人睡觉。在调解模型中,室外日光暴露与WHO-5/PHQ-9得分相关,当每天暴露时,总效应较高(β=4.13±0.53/β=-3.81±0.67),超过4小时(β=3.77±0.91/β=-3.83±1.31)和早晨(β=3.41±0.53/β=-3.74±0.70),以缺乏暴露。时间型估计,常规规律性评分,睡眠问题充当了中介,而社交时差和睡眠持续时间在这种关联中没有发挥重要作用。这项研究促进了对光照之间复杂相互作用的理解,心理健康,以及睡眠的个体特征和其他常规规律,并显示了优化日光照射以改善心理健康的好处。
    The light/dark cycle is the main external cue to synchronize the human biological clock. Modern lifestyles typically lead to less daylight exposure and blunted 24 h-amplitude. We evaluated the association of outdoor daylight exposure (frequency, duration, regularity and shift) with chronotype estimated by sleep phase, regularity of routines, sleep, well-being (WHO-5), and depressive symptoms (PHQ-9), in a sample of 1,095 participants (81.8% female; 87.9% aged 18-49) surveyed online between July and November 2020. We analyzed direct and indirect associations in daylight-mood relationship with chronotype-estimate, routine regularity, and sleep as mediators. Outdoor daylight exposure was associated with WHO-5/PHQ-9 scores in mediation models, with higher total effects when the exposure was every day (β = 4.13 ± 0.53/ β = -3.81 ± 0.67), for more than 4 hours (β = 3.77 ± 0.91/ β = -3.83 ± 1.31) and during the morning (β = 3.41 ± 0.53/ β = -3.74 ± 0.70) in reference to lack of exposure. Chronotype-estimate, routine regularity score, and sleep problems acted as mediators, while social jetlag and sleep duration did not play an important role in this association. This study advanced the understanding of the complex interplay between light exposure, mental health, and individual characteristics of sleep and other routine regularities, and showed the benefits of optimizing daylight exposure to improve mental health.
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  • 文章类型: Journal Article
    作为生物体的中央调控系统,大脑负责监督生物体生存所必需的各种生理过程。为了维持神经元发挥作用所必需的环境,大脑需要通过血脑屏障(BBB)高度选择性地摄取和消除特定分子。由于生物体的活动在一天中各不相同,血脑屏障如何适应大脑不断变化的需求?一种机制是通过昼夜节律对血脑屏障通透性进行时间调节,这将是本章的重点。为了理解生物钟在血脑屏障中的作用,我们将首先检查BBB的解剖结构和运输机制,使其能够发挥其作为限制性屏障的作用。接下来,我们将定义生物钟,讨论将包括对昼夜节律的介绍,转录-翻译反馈环(TTFL)作为昼夜节律计时的机制基础,以及在生物体中发现的组织钟的组织。然后,我们将介绍昼夜节律在调节BBB的细胞机制和功能中的作用。我们讨论了这种调节对影响睡眠行为的影响,神经退行性疾病的进展,最后是治疗神经系统疾病的药物递送。
    As the central regulatory system of an organism, the brain is responsible for overseeing a wide variety of physiological processes essential for an organism\'s survival. To maintain the environment necessary for neurons to function, the brain requires highly selective uptake and elimination of specific molecules through the blood-brain barrier (BBB). As an organism\'s activities vary throughout the day, how does the BBB adapt to meet the changing needs of the brain? A mechanism is through temporal regulation of BBB permeability via its circadian clock, which will be the focal point of this chapter. To comprehend the circadian clock\'s role within the BBB, we will first examine the anatomy of the BBB and the transport mechanisms enabling it to fulfill its role as a restrictive barrier. Next, we will define the circadian clock, and the discussion will encompass an introduction to circadian rhythms, the Transcription-Translation Feedback Loop (TTFL) as the mechanistic basis of circadian timekeeping, and the organization of tissue clocks found in organisms. Then, we will cover the role of the circadian rhythms in regulating the cellular mechanisms and functions of the BBB. We discuss the implications of this regulation in influencing sleep behavior, the progression of neurodegenerative diseases, and finally drug delivery for treatment of neurological diseases.
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