Browsing by Subject "Circadian rhythm"
Now showing 1 - 9 of 9
Results Per Page
Sort Options
Item A National Survey of U.S. Adolescent Sleep Duration, Timing, and Social Jetlag During the COVID-19 Pandemic(Taylor & Francis, 2023) Wesley, Katherine L.; Cooper, Emily H.; Brinton, John T.; Meier, Maxene; Honaker, Sarah; Simon, Stacey L.; Pediatrics, School of MedicineObjectives: To assess changes in duration, timing, and social jetlag in adolescent sleep during the COVID-19 pandemic and evaluate the impact of mood, physical activity, and social interactions on sleep. Study design: An online survey queried adolescents' sleep before (through retrospective report) and during the initial phase of COVID-19 in May 2020. Adolescents (N = 3,494), 13-19 years old, in the United States (U.S.) answered questions about their current and retrospective (prior to COVID-19) sleep, chronotype, mood, and physical and social activities. Linear regression models were fit for time in bed, reported bed and wake times, and social jetlag during COVID-19, accounting for pre-COVID-19 values. Results: Total reported time in bed (a proxy for sleep duration) increased on weekdays by an average of 1.3 ± 1.8 hours (p < .001) during COVID-19, compared to retrospective report of time in bed prior to COVID-19. During COVID-19, 81.3% of adolescents reported spending 8 hours or more in bed on weekdays compared to only 53.5% prior to COVID-19. On weekdays, bedtimes were delayed on average by 2.5 hours and wake times by 3.8 hours during COVID-19 compared to prior to COVID-19. On weekends, bedtimes were delayed on average by 1.6 hours and waketimes by 1.5 hours (all p's < 0.001). Social jetlag of >2 hours decreased to 6.3% during COVID-19 compared to 52.1% prior to COVID-19. Anxiety and depression symptoms and a decline in physical activity during COVID-19 were associated with delayed bed and wake times during COVID-19. Conclusions: During COVID-19, adolescents reported spending more time in bed, with most adolescents reporting 8 hours of sleep opportunity and more consistent sleep schedules. As schools return to in-person learning, additional research should examine how sleep schedules may change due to school start times and what lessons can be learned from changes that occurred during COVID-19 that promote favorable adolescent sleep.Item Circadian rhythms in bipolar disorder patient-derived neurons predict lithium response: Preliminary studies(Springer Nature, 2021) Mishra, Himanshu K.; Ying, Noelle M.; Luis, Angelica; Wei, Heather; Nguyen, Metta; Nakhla, Timothy; Vandenburgh, Sara; Alda, Martin; Berrettini, Wade H.; Brennand, Kristen J.; Calabrese, Joseph R.; Coryell, William H.; Frye, Mark A.; Gage, Fred H.; Gershon, Elliot S.; McInnis, Melvin G.; Nievergelt, Caroline M.; Nurnberger, John I.; Shilling, Paul D.; Oedegaard, Ketil J.; Zandi, Peter P.; The Pharmacogenomics of Bipolar Disorder Study; Kelsoe, John R.; Welsh, David K.; McCarthy, Michael J.; Psychiatry, School of MedicineBipolar disorder (BD) is a neuropsychiatric illness defined by recurrent episodes of mania/hypomania, depression and circadian rhythm abnormalities. Lithium is an effective drug for BD, but 30–40% of patients fail to respond adequately to treatment. Previous work has demonstrated that lithium affects the expression of “clock genes” and that lithium responders (Li-R) can be distinguished from non-responders (Li-NR) by differences in circadian rhythms. However, circadian rhythms have not been evaluated in BD patient neurons from Li-R and Li-NR. We used induced pluripotent stem cells (iPSCs) to culture neuronal precursor cells (NPC) and glutamatergic neurons from BD patients characterized for lithium responsiveness and matched controls. We identified strong circadian rhythms in Per2-luc expression in NPCs and neurons from controls and Li-R, but NPC rhythms in Li-R had a shorter circadian period. Li-NR rhythms were low-amplitude and profoundly weakened. In NPCs and neurons, expression of PER2 was higher in both BD groups compared to controls. In neurons, PER2 protein levels were higher in BD than controls, especially in Li-NR samples. In single cells, NPC and neuron rhythms in both BD groups were desynchronized compared to controls. Lithium lengthened period in Li-R and control neurons but failed to alter rhythms in Li-NR. In contrast, temperature entrainment increased amplitude across all groups, and partly restored rhythms in Li-NR neurons. We conclude that neuronal circadian rhythm abnormalities are present in BD and most pronounced in Li-NR. Rhythm deficits in BD may be partly reversible through stimulation of entrainment pathways.Item The Diurnal Rhythm of Insulin Receptor Substrate-1 (IRS-1) and Kir4.1 in Diabetes: Implications for a Clock Gene Bmal1(ARVO, 2019-05) Luo, Qianyi; Xiao, Yucheng; Alex, Alpha; Cummins, Theodore R.; Bhatwadekar, Ashay D.; Ophthalmology, School of MedicinePurpose: Diabetes leads to the downregulation of the retinal Kir4.1 channels and Müller cell dysfunction. The insulin receptor substrate-1 (IRS-1) is a critical regulator of insulin signaling in Müller cells. Circadian rhythms play an integral role in normal physiology; however, diabetes leads to a circadian dysrhythmia. We hypothesize that diabetes will result in a circadian dysrhythmia of IRS-1 and Kir4.1 and disturbed clock gene function will have a critical role in regulating Kir4.1 channels. Methods: We assessed a diurnal rhythm of retinal IRS-1 and Kir4.1 in db/db mice. The Kir4.1 function was evaluated using a whole-cell recording of Müller cells. The rat Müller cells (rMC-1) were used to undertake in vitro studies using a siRNA. Results: The IRS-1 exhibited a diurnal rhythm in control mice; however, with diabetes, this natural rhythm was lost. The Kir4.1 levels peaked and troughed at times similar to the IRS-1 rhythm. The IRS-1 silencing in the rMC-1 led to a decrease in Kir4.1 and BMAL1. The insulin treatment of retinal explants upregulated Kir4.1 possibly via upregulation of BMAL1 and phosphorylation of IRS-1 and Akt-1. Conclusions: Our studies highlight that IRS-1, by regulating BMAL1, is an important regulator of Kir4.1 in Müller cells and the dysfunctional signaling mediated by IRS-1 may be detrimental to Kir4.1.Item Drugs of Abuse Can Entrain Circadian Rhythms(Hindawi Publishing Corporation, 2007-11-02) Kosobud, Ann E.K.; Gillman, Andrea G.; Leffel, Joseph K., II; Pecoraro, Norman C.; Rebec, G.V.; Timberlake, William; Neurology, School of MedicineCircadian rhythms prepare organisms for predictable events during the Earth's 24-h day. These rhythms are entrained by a variety of stimuli. Light is the most ubiquitous and best known zeitgeber, but a number of others have been identified, including food, social cues, locomotor activity, and, most recently drugs of abuse. Given the diversity of zeitgebers, it is probably not surprising that genes capable of clock functions are located throughout almost all organs and tissues. Recent evidence suggests that drugs of abuse can directly entrain some circadian rhythms. We have report here that entrainment by drugs of abuse is independent of the suprachiasmatic nucleus and the light/dark cycle, is not dependent on direct locomotor stimulation, and is shared by a variety of classes of drugs of abuse. We suggest that drug-entrained rhythms reflect variations in underlying neurophysiological states. This could be the basis for known daily variations in drug metabolism, tolerance, and sensitivity to drug reward. These rhythms could also take the form of daily periods of increased motivation to seek and take drugs, and thus contribute to abuse, addiction and relapse.Item Mapping the daily rhythmic transcriptome in the diabetic retina(Elsevier, 2024) Silk, Ryan P.; Winter, Hanagh R.; Dkhissi-Benyahya, Ouria; Evans-Molina, Carmella; Stitt, Alan W.; Tiwari, Vijay K.; Simpson, David A.; Beli, Eleni; Medicine, School of MedicineRetinal function changes dramatically from day to night, yet clinical diagnosis, treatments, and experimental sampling occur during the day. To begin to address this gap in our understanding of disease pathobiology, this study investigates whether diabetes affects the retina's daily rhythm of gene expression. Diabetic, Ins2Akita/J mice, and non-diabetic littermates were kept under a 12 h:12 h light/dark cycle until 4 months of age. mRNA sequencing was conducted in retinas collected every 4 h throughout the 24 hr light/dark cycle. Computational approaches were used to detect rhythmicity, predict acrophase, identify differential rhythmic patterns, analyze phase set enrichment, and predict upstream regulators. The retinal transcriptome exhibited a tightly regulated rhythmic expression with a clear 12-hr transcriptional axis. Day-peaking genes were enriched for DNA repair, RNA splicing, and ribosomal protein synthesis, night-peaking genes for metabolic processes and growth factor signaling. Although the 12-hr transcriptional axis is retained in the diabetic retina, it is phase advanced for some genes. Upstream regulator analysis for the phase-shifted genes identified oxygen-sensing mechanisms and HIF1alpha, but not the circadian clock, which remained in phase with the light/dark cycle. We propose a model in which, early in diabetes, the retina is subjected to an internal desynchrony with the circadian clock and its outputs are still light-entrained whereas metabolic pathways related to neuronal dysfunction and hypoxia are phase advanced. Further studies are now required to evaluate the chronic implications of such desynchronization on the development of diabetic retinopathy.Item Modeling bivariate longitudinal hormone profiles by hierarchical state space models(Taylor & Francis, 2014-01-01) Liu, Ziyue; Cappola, Anne R.; Crofford, Leslie J.; Guo, Whensheng; Department of Medicine, IU School of MedicineThe hypothalamic-pituitary-adrenal (HPA) axis is crucial in coping with stress and maintaining homeostasis. Hormones produced by the HPA axis exhibit both complex univariate longitudinal profiles and complex relationships among different hormones. Consequently, modeling these multivariate longitudinal hormone profiles is a challenging task. In this paper, we propose a bivariate hierarchical state space model, in which each hormone profile is modeled by a hierarchical state space model, with both population-average and subject-specific components. The bivariate model is constructed by concatenating the univariate models based on the hypothesized relationship. Because of the flexible framework of state space form, the resultant models not only can handle complex individual profiles, but also can incorporate complex relationships between two hormones, including both concurrent and feedback relationship. Estimation and inference are based on marginal likelihood and posterior means and variances. Computationally efficient Kalman filtering and smoothing algorithms are used for implementation. Application of the proposed method to a study of chronic fatigue syndrome and fibromyalgia reveals that the relationships between adrenocorticotropic hormone and cortisol in the patient group are weaker than in healthy controls.Item Prolonged Administration of Melatonin Ameliorates Liver Phenotypes in Cholestatic Murine Model(Elsevier, 2022) Ceci, Ludovica; Chen, Lixian; Baiocchi, Leonardo; Wu, Nan; Kennedy, Lindsey; Carpino, Guido; Kyritsi, Konstantina; Zhou, Tianhao; Owen, Travis; Kundu, Debjyoti; Sybenga, Amelia; Isidan, Abdulkadir; Ekser, Burcin; Franchitto, Antonio; Onori, Paolo; Gaudio, Eugenio; Mancinelli, Romina; Francis, Heather; Alpini, Gianfranco; Glaser, Shannon; Medicine, School of MedicineBackground & aims: Primary sclerosing cholangitis (PSC) is characterized by biliary senescence and hepatic fibrosis. Melatonin exerts its effects by interacting with Melatonin receptor 1 and 2 (MT1/MT2) melatonin receptors. Short-term (1 wk) melatonin treatment reduces a ductular reaction and liver fibrosis in bile duct-ligated rats by down-regulation of MT1 and clock genes, and in multidrug resistance gene 2 knockout (Mdr2-/-) mice by decreased miR200b-dependent angiogenesis. We aimed to evaluate the long-term effects of melatonin on liver phenotype that may be mediated by changes in MT1/clock genes/miR200b/maspin/glutathione-S transferase (GST) signaling. Methods: Male wild-type and Mdr2-/- mice had access to drinking water with/without melatonin for 3 months. Liver damage, biliary proliferation/senescence, liver fibrosis, peribiliary inflammation, and angiogenesis were measured by staining in liver sections, and by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay in liver samples. We confirmed a link between MT1/clock genes/miR200b/maspin/GST/angiogenesis signaling by Ingenuity Pathway Analysis software and measured liver phenotypes and the aforementioned signaling pathway in liver samples from the mouse groups, healthy controls, and PSC patients and immortalized human PSC cholangiocytes. Results: Chronic administration of melatonin to Mdr2-/- mice ameliorates liver phenotypes, which were associated with decreased MT1 and clock gene expression. Conclusions: Melatonin improves liver histology and restores the circadian rhythm by interaction with MT1 through decreased angiogenesis and increased maspin/GST activity.Item Quantitative Trait Locus Determining the Time of Blood Feeding in Culex pipiens (Diptera: Culicidae)(Oxford University Press, 2022) Hickner, Paul V.; Mori, Akio; Rund, Samuel S. C.; Severson, David W.; Medical and Molecular Genetics, School of MedicineMosquitoes and other blood feeding arthropods are vectors of pathogens causing serious human diseases, such as Plasmodium spp. (malaria), Wuchereria bancrofti (lymphatic filariasis), Borrelia burgdorferi (Lyme disease), and viruses causing dengue, Zika, West Nile, chikungunya, and yellow fever. Among the most effective strategies for the prevention of vector-borne diseases are those aimed at reducing human-vector interactions, such as insecticide applications and insecticide-treated bed nets (ITNs). In some areas where ITNs are widely used, behavioral adaptations have resulted in mosquitoes shifting their time of blood feeding to earlier or later in the night when the bed nets are not being employed. Little is known about the genetic basis of these behavioral shifts. We conducted quantitative trait locus (QTL) analysis using two strains of Culex pipiens sensu lato with contrasting blood feeding behaviors, wherein the lab adapted Shasta strain blood feeds at any time of the day or night, while the newly established Trinidad strain feeds only at night. We identified a single locus on chromosome 2 associated with the observed variation in feeding times. None of the core clock genes period, timeless, clock, cycle, PAR-domain protein 1, vrille, discs overgrown, cryptochrome 1, or cryptochrome 2 were located within the QTL region. We then monitored locomotor behavior to determine if they differed in their flight activity. The highly nocturnal Trinidad strain showed little daytime activity while the day-feeding Shasta strain was active during the day, suggesting blood feeding behavior and flight activity are physiologically linked.Item Variants in Ion Channel Genes Link Phenotypic Features of Bipolar Illness to Specific Neurobiological Process Domains(Karger, 2015-05) Balaraman, Yokesh; Lahiri, Debomoy K.; Nurnberger, John I.; Department of Psychiatry, IU School of MedicineRecent advances in genome-wide association studies are pointing towards a major role for voltage-gated ion channels in neuropsychiatric disorders and, in particular, bipolar disorder (BD). The phenotype of BD is complex, with symptoms during mood episodes and deficits persisting between episodes. We have tried to elucidate the common neurobiological mechanisms associated with ion channel signaling in order to provide a new perspective on the clinical symptoms and possible endophenotypes seen in BD patients. We propose a model in which the multiple variants in genes coding for ion channel proteins would perturb motivational circuits, synaptic plasticity, myelination, hypothalamic-pituitary-adrenal axis function, circadian neuronal rhythms, and energy regulation. These changes in neurobiological mechanisms would manifest in endophenotypes of aberrant reward processing, white matter hyperintensities, deficits in executive function, altered frontolimbic connectivity, increased amygdala activity, increased melatonin suppression, decreased REM latency, and aberrant myo-inositol/ATP shuttling. The endophenotypes result in behaviors of poor impulse control, motivational changes, cognitive deficits, abnormal stress response, sleep disturbances, and energy changes involving different neurobiological process domains. The hypothesis is that these disturbances start with altered neural circuitry during development, following which multiple environmental triggers may disrupt the neuronal excitability balance through an activity-dependent molecular process, resulting in clinical mood episodes.