Journal of Biological Rhythms最新文献

{"title":"Neurotransmitter and Receptor Mapping in <i>Drosophila</i> Circadian Clock Neurons via T2A-GAL4 Screening.","authors":"Ayumi Fukuda, Aika Saito, Taishi Yoshii","doi":"10.1177/07487304251349887","DOIUrl":"10.1177/07487304251349887","url":null,"abstract":"<p><p>The circadian neuronal network in the brain comprises central pacemaker neurons and associated input and output pathways. These components work together to generate coherent rhythmicity, synchronize with environmental time cues, and convey circadian information to downstream neurons that regulate behaviors such as the sleep/wake cycle. To mediate these functions, neurotransmitters and neuromodulators play essential roles in transmitting and modulating signals between neurons. In <i>Drosophila melanogaster</i>, approximately 240 brain neurons function as clock neurons. Previous studies have identified several neurotransmitters and neuromodulators, including the Pigment-dispersing factor (PDF) neuropeptide, along with their corresponding receptors in clock neurons. However, our understanding of the neurotransmitters and receptors involved in the circadian system remains incomplete. In this study, we conducted a T2A-GAL4-based screening for neurotransmitter and receptor genes expressed in clock neurons. We identified 2 neurotransmitter-related genes and 22 receptor genes. Notably, while previous studies had reported the expression of 6 neuropeptide receptor genes in large ventrolateral neurons (l-LN_v), we also found that 14 receptor genes-including those for dopamine, serotonin, and γ-aminobutyric acid-are expressed in l-LN_v neurons. These findings suggest that l-LN_v neurons serve as key integrative hubs within the circadian network, receiving diverse external signals.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"491-497"},"PeriodicalIF":2.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time of Day-Dependent Responses to Cisplatin Treatment in a Male Mouse Model of Hepatoma.","authors":"Yasemin Kubra Akyel, Christopher P Selby, Aziz Sancar, Ashraf N Abdo","doi":"10.1177/07487304251349893","DOIUrl":"10.1177/07487304251349893","url":null,"abstract":"<p><p>The circadian clock maintains oscillations in gene expression with a 24-hour periodicity in nearly every cell of the body and confers rhythmic patterns to many aspects of behavior and physiology. The presence of circadian rhythms in tumors leads to the question of whether tumors may respond differently to chemotherapy given at different times of day. We addressed this question using a male mouse model of hepatoma by treating mice in the morning (ZT2) or evening (ZT14) with cisplatin, and measuring gross effects on body weight, blood counts and chemistry, gene expression, and cellular proliferation. We found that among cisplatin-treated mice, there was a reduction in expression of the proliferation marker protein Ki-67 in tumors of mice treated at ZT14 as compared to ZT2. Corresponding hepatotoxicity, as measured by elevated serum alanine aminotransferase (ALT), and body weight loss were also reduced at ZT14. Overall gene expression at ZT14 was more similar to healthy liver than expression at ZT2. Mitogen-activated protein kinase (MAPK) and Ras-related protein-1 (Rap-1) signaling pathways were specifically downregulated in tumors following treatment at ZT14, which may be related to the decreased proliferation, at this treatment time. These findings align with the possible use of timed chemotherapy to enhance drug efficacy.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"441-454"},"PeriodicalIF":2.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian Control of Pulmonary Endothelial Signaling Occurs via the NADPH Oxidase 2-NLRP3 Pathway.","authors":"Shaon Sengupta, Yool Lee, Jian Qin Tao, Isha Akolia, Natalia Louneva, Kaitlyn Forrest, Oindrila Paul, Thomas G Brooks, Gregory R Grant, Amita Sehgal, Shampa Chatterjee","doi":"10.1177/07487304251363656","DOIUrl":"10.1177/07487304251363656","url":null,"abstract":"<p><p>Circadian rhythms are endogenous oscillations that occur with a 24-h periodicity and support organismal homeostasis. While the role of the circadian clock in systemic vasculature is well known, its role in pulmonary vasculature, specifically in the pulmonary endothelium, has remained unexplored. We hypothesized that the circadian clock directly regulates pulmonary endothelium to control lung inflammation. Using pulmonary artery segments and endothelial cells isolated from lungs of mPer2luciferase transgenic mice, we monitored circadian rhythms and observed that lipopolysaccharide (LPS) treatment disrupted rhythmicity. This disruption was mediated by reactive oxygen species (ROS) generated via NADPH oxidase 2 (NOX2). Remarkably, the pharmacologic inhibition of NOX2 before LPS exposure restored circadian rhythmicity in the pulmonary endothelium. In wild-type (WT) mice, LPS activated a NOX2-NLRP3 signaling axis that drove inflammation as evidenced by increased polymorphonuclear neutrophil (PMN) accumulation and intercellular adhesion molecule-1 (ICAM-1) expression on the pulmonary endothelium. In contrast, disruption of the clock using two different clock mutants (<i>Bmal</i>1^-/- and <i>Cry1/2</i>^-/-) resulted in a sustained baseline elevation of PMN and ICAM-1, which changed minimally with LPS. This effect was attributed to aberrant activation of the NLRP3 inflammasome at baseline in the clock mutants, as supported by lung transcriptomic data and reversal of the phenotype with an NLRP3 inhibitor. Importantly, these findings also reveal an intriguing bidirectional relationship: while the circadian clock modulates inflammatory responses, inflammatory stimuli in turn alter circadian rhythmicity via the NOX2 pathway. Together, our results identify a novel mechanism by which circadian control of pulmonary endothelial inflammation may be leveraged to mitigate the consequences of clock disruption in lung disease.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304251363656"},"PeriodicalIF":2.1,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12499374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of Blood-Based Biomarkers for Human Circadian Pacemaker Phase: Training Sets Matter As Much As Feature-Selection Methods.","authors":"Carla S Möller-Levet, Simon N Archer, Derk-Jan Dijk","doi":"10.1177/07487304251358950","DOIUrl":"https://doi.org/10.1177/07487304251358950","url":null,"abstract":"<p><p>Biomarkers are valuable tools in a wide range of human health areas including circadian medicine. Valid, low-burden, multivariate molecular approaches to assess circadian phase at scale in people living and working in the real world hold promise for translating basic circadian knowledge to practical applications. However, standards for the development and evaluation of these circadian biomarkers have not yet been established, even though several publications report such biomarkers and claim that the methods are universal. Here, we present a basic exploration of some of the determinants and confounds of blood-based biomarker development for suprachiasmatic nucleus (SCN) phase by reanalysing publicly available data sets. We compare performance of biomarkers based on three feature-selection methods: Partial Least Squares Regression, ZeitZeiger, and Elastic Net, as well as performance of a standard set of clock genes. We explore the effects of training sample size and the impact of the experimental protocols from which training samples are drawn and on which performance is tested. Approaches based on small sample sizes used for training are prone to poor performance due to overfitting. Performance to some extent depends on the feature-selection method, but at least as much on the experimental conditions from which the biomarker training samples were drawn. Performance of biomarkers developed under baseline conditions does not necessarily translate to protocols that mimic real-world scenarios such as shiftwork in which sleep may be restricted or desynchronized from the endogenous circadian SCN phase. The molecular features selected by the various approaches to develop biomarkers for the SCN phase show very little overlap although the processes associated with these features have common themes with response to steroid hormones, that is, cortisol being the most prominent. Overall, the findings indicate that establishment of circadian biomarkers should be guided by established biomarker-development concepts and foundational principles of human circadian biology.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304251358950"},"PeriodicalIF":2.1,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>miR-124</i> acts During <i>Drosophila</i> Development to Determine the Phase of Adult Circadian Behavior.","authors":"Yongliang Xia, Chenghao Chen, Patrick Emery","doi":"10.1177/07487304251361579","DOIUrl":"10.1177/07487304251361579","url":null,"abstract":"<p><p>The circadian clock enables organisms to optimize their metabolism, physiology, and behavior with the time-of-day. However, circadian rhythms benefit organisms only if they are properly synchronized with the day/night cycle; circadian misalignment can have detrimental effects on animals' wellbeing and survival. We previously showed that in <i>Drosophila</i>, loss of the microRNA <i>miR-124</i> advances the phase of circadian evening locomotor activity by several hours under constant darkness conditions. Interestingly, we now report that loss of <i>miR-124</i> also delays morning activity under a light/dark cycle with a short photoperiod. We recapitulated these opposite phase phenotypes by eliminating <i>miR-124</i> during larval development, but not when this microRNA is lost during pupation to adulthood. The loss of <i>miR-124</i> results in significant miswiring within the circadian neural network and severely alters neural activity rhythms in the ventral Lateral Neurons (s-LNvs) and the posterior Dorsal Neurons 1 (DN1ps), which control the timing of morning and evening activity. Silencing the s-LNvs in <i>miR-124</i> mutant flies restores the phase of evening activity, while activating the DN1ps rescues the phases of both morning and evening activities. Our findings thus reveal the pivotal role of <i>miR-124</i> in sculpting the <i>Drosophila</i> circadian neural network during development and its long-lasting impact on circuit activity and adult circadian behavior.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304251361579"},"PeriodicalIF":2.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Jules Verne: A Literary Pioneer of Chronobiology.","authors":"Diego A Golombek","doi":"10.1177/07487304251369951","DOIUrl":"https://doi.org/10.1177/07487304251369951","url":null,"abstract":"","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304251369951"},"PeriodicalIF":2.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotic-induced Dysbiosis of Gut Microbiota Increases Food Motivation and Anticipatory Activity Under a Time-restricted Feeding Protocol.","authors":"Manuel T Crespo, Alana Del Rio, Cristina Borio, Marcos Bilen, Juan J Chiesa, Patricia V Agostino","doi":"10.1177/07487304251359349","DOIUrl":"https://doi.org/10.1177/07487304251359349","url":null,"abstract":"<p><p>Newly emerging evidence underscores the crucial role of the gut microbiota in regulating various aspects of mammalian physiology and behavior, including circadian rhythms. These rhythms, fundamental to behavioral and physiological processes, are orchestrated by a circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Extra-SCN oscillators have been identified in brain regions beyond the SCN and in peripheral tissues temporizing wide physiological functions. Under a 12 h light: 12 h dark cycle (12:12 LD), restriction of food access to hours of light in nocturnal animals in a time-restricted feeding (TRF) protocol increases locomotor activity preceding the scheduled daily meal, so-called food anticipatory activity (FAA). This circadian behavior is independent from the SCN and controlled by a food-entrainable oscillator (FEO) dependent on reward-related signals. It is known that signals from the gut microbiota regulate behaviors such as motivation oriented by food reward. Thus, we hypothesized a physiological link between gut microbiota and FEO activity by studying the circadian FAA behavior under TRF and assessing food-oriented motivational behavior. For that aim, C57BL/6J mice treated with antibiotics for generating gut microbiota dysbiosis were subjected to a 3 h TRF protocol at zeitgeber time (ZT) 4-7. Mice treated with antibiotics exhibited greater FAA, lower time for its consolidation, and greater motivation levels for food reward. Moreover, tyrosine hydroxylase (TH) levels were increased in the nucleus accumbens (NAc) and ventral tegmental area (VTA) of antibiotic-treated mice. Finally, changes in the gut microbiota composition-including bacterial diversity and the abundance of certain genera-were observed. These results suggest that gut microbiota has a regulatory role in the circadian motivational output for food reward controlled by the FEO. Understanding this role is important for potential chronotherapeutics targeting gut microbiota in reward-related alterations such as addictions and eating disorders.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304251359349"},"PeriodicalIF":2.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144846599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Day Length on Brain Glucose Metabolism in Men: A Large-Scale Repeated Measures PET Study.","authors":"Kyoungjune Pak, Seunghyeon Shin, Keunyoung Kim, Jihyun Kim, Hyun-Yeol Nam, Lauri Nummenmaa, Pirjo Nuutila, Xingdang Liu, Lihua Sun","doi":"10.1177/07487304251360874","DOIUrl":"https://doi.org/10.1177/07487304251360874","url":null,"abstract":"<p><p>The brain is the most energy-demanding organ, yet whether cerebral energy homeostasis exhibits seasonal rhythmicity remains unclear. In this study, 432 healthy men underwent a health checkup program with fasting-state brain [¹⁸F]fluorodeoxyglucose positron emission tomography (PET) scanning twice: first at the baseline and then at the 5-year follow-up. We analyzed the effect of day length on brain glucose uptake separately for both time points. In both baseline and follow-up scans, day length on the day of imaging significantly predicted glucose uptake in the socio-emotional circuit. A longer day length was associated with increased glucose uptake in the cuneus, precuneus, orbitofrontal cortex, pre- and postcentral gyrus, superior and middle temporal gyrus, posterior cingulate cortex, insula, and frontal pole. This large-scale longitudinal PET study provides landmark evidence for the impact of daylight exposure on brain glucose metabolism. Findings disclose the baseline seasonal variation of brain energy consumption in men.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304251360874"},"PeriodicalIF":2.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep Identification Enabled by Supervised Training Algorithms (SIESTA): An Open-Source Platform for Automatic Sleep Staging of Rodent Electrocorticographic and Electromyographic Data.","authors":"Asad I Beck, Carlos S Caldart, Miriam Ben-Hamo, Tenley A Weil, Jazmine G Perez, Franck Kalume, Bingni W Brunton, Horacio O de la Iglesia, Raymond E A Sanchez","doi":"10.1177/07487304251336649","DOIUrl":"10.1177/07487304251336649","url":null,"abstract":"<p><p>Accurately capturing the temporal distribution of polysomnographic sleep stages is critical for the study of sleep function, regulation, and disorders in higher vertebrates. In laboratory rodents, scoring of electrocorticography (ECoG) and electromyography (EMG) recordings is usually performed manually by categorizing 5- to 10-sec epochs as 1 of 3 specific stages: wakefulness, rapid-eye-movement (REM) sleep, and non-REM (NREM) sleep. This process is laborious, time-consuming, and particularly impractical for large experimental cohorts with recordings lasting longer than 24 h, which are critical for the study of the circadian regulation of sleep. To circumvent this problem, we developed an open-source Python toolkit, Sleep Identification Enabled by Supervised Training Algorithms (SIESTA), that automates the detection of these 3 main behavioral stages in mice. We used a supervised machine learning algorithm that extracts features from the ECoG and EMG signals and autonomously scores recordings with a hierarchical classifier based on using logistic regression. We evaluated this approach on data collected from wild-type mice housed under both normal and different lighting conditions, as well as from mutant mouse lines with abnormal sleep phenotypes and from rats. We obtained mean F₁ scores 0.94 for wakefulness, 0.94 for NREM, and 0.74 for REM, and followed up by validating SIESTA with manually scored data from 3 other laboratories. SIESTA has a user-friendly interface that can be used without coding expertise. To our knowledge, this is the first time that such a strategy has been developed using all open-source and freely available resources. Our aim is that SIESTA becomes a useful tool that facilitates further research in sleep on rodent models.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"330-346"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Phase Shifts Are Associated With Higher Systolic Blood Pressure and Impaired Glucose Tolerance Independently of Estrogen Deficiency in Female Spontaneously Hypertensive Rats.","authors":"Refentshe Amandu's Nthlane, Karine Scheuermaier, Siluleko Advice Mkhize, Frédéric Sébastien Michel","doi":"10.1177/07487304251347464","DOIUrl":"10.1177/07487304251347464","url":null,"abstract":"<p><p>Postmenopausal shift workers face increased cardiometabolic risk due to estrogen decline and shift work-induced circadian misalignment. Yet, their combined effects remain poorly understood, especially in hypertensive individuals. This study investigated whether circadian misalignment worsens cardiometabolic parameters in a hypertensive ovariectomized rat model. Female spontaneously hypertensive rats (SHR) were ovariectomized or sham-operated (7-week-old), and then exposed to a chronic phase shift (CPS) protocol or a control light schedule for 10 weeks (<i>n</i> = 9 per group). Measurements included body mass, food and water intake, blood pressure (BP), fasting glucose, glucose tolerance, organ masses, and low-density lipoprotein (LDL) concentration. Ovariectomized rats were heavier and had greater food intake and organ masses than sham-operated rats. However, food intake and organ masses were reduced relative to body mass. CPS rats had greater water intake and reduced liver mass than control light rats. In addition, ovariectomized rats showed lower glucose concentration than sham-operated rats, whereas CPS rats showed higher glucose concentration than control light rats during the oral glucose tolerance test. Moreover, the CPS rats had higher systolic BP. The LDL and fasting glucose concentrations were similar. No interaction between ovariectomy and CPS was observed. These findings suggest that estrogen deficiency increases body mass, but does not worsen cardiometabolic parameters in female SHR. CPS-induced circadian misalignment altered water intake, liver mass, systolic BP and glucose tolerance in the CPS condition in female SHR. This study was unable to monitor physiological or behavioral indicators to confirm circadian misalignment by the CPS protocol. However, the findings provide novel insights into how CPSs independently impair cardiometabolic outcomes in female SHR, with implications for understanding risk in postmenopausal shift workers.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"384-399"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}