scholarly journals Chronic caffeine treatment disrupts the circadian rhythm in Drosophila

2021 ◽  
Author(s):  
Aishwarya Segu ◽  
Nisha N Kannan
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Daily Basis ◽  
Caffeine Intake ◽  
Constant Darkness ◽  
Homeostatic Regulation ◽  
Caffeine Treatment ◽  
Chronic Caffeine ◽  
Anticipatory Activity ◽  
Free Running Period

The circadian clock governs the timing of sleep-wake cycles as well as of other behavioural, physiological and metabolic processes. While the endogenous circadian clock mediates the timing of sleep, homeostatic mechanisms modulate the amount and depth of sleep. Evidence from previous studies showed that caffeine intake promotes wakefulness, whereas adult-stage specific caffeine treatment not only suppresses sleep but also delays the phase of circadian rhythm in Drosophila. In humans, caffeine is consumed on a daily basis and hence it is important to understand the effect of prolonged caffeine intake on circadian and homeostatic regulation of sleep. In the present study we examined the differential effect of acute and chronic caffeine treatment on sleep ontogeny as well as on circadian and homeostatic regulation of sleep in Drosophila. The results of our study showed that acute caffeine treatment reduces day and night sleep in mature flies through the homeostatic pathway whereas it reduced only the day sleep in young flies. Chronic caffeine treatment did not exert any significant effect on sleep in young flies. On the other hand, it delayed the timing of sleep in mature flies and in addition flies under higher caffeine concentration reduced the morning and evening anticipatory activity under 12 hour: 12 hour light: dark cycles. These flies also exhibited either a longer free running period or arrhythmicity under constant darkness. The results of our study showed that acute caffeine treatment suppresses sleep through the homeostatic pathway whereas prolonged caffeine treatment disrupts the circadian rhythm in mature flies.

Altered hormone levels and circadian rhythm of activity in the WKY rat, a putative animal model of depression

2001 ◽  
Vol 281 (3) ◽  
pp. R786-R794 ◽  
Author(s):  
Leah C. Solberg ◽  
Susan Losee Olson ◽  
Fred W. Turek ◽  
Eva Redei
Keyword(s):  
Circadian Rhythm ◽  
Wistar Rats ◽  
Depressive Disorders ◽  
Rat Plasma ◽  
Thyroid Stimulating Hormone ◽  
Constant Darkness ◽  
Wky Rats ◽  
Animal Model Of Depression ◽  
Wistar Kyoto ◽  
Free Running Period

The Wistar Kyoto (WKY) rat is hyperreactive to stress and exhibits depressive-like behavior in several standard behavioral tests. Because patients with depressive disorders often exhibit disruptions in the circadian rhythm of activity, as well as altered secretory patterns of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid hormones, we tested the hypothesis that these phenomena occur in the WKY rat. Plasma ACTH and corticosterone levels remained significantly higher after the diurnal peak for several hours in WKY rats relative to Wistar rats. Also, plasma levels of thyroid-stimulating hormone were significantly higher in WKY relative to Wistar rats across the 24-h period, despite normal or slightly higher levels of 3,5,3′-triiodothyronine. In addition, under constant darkness conditions, WKY rats exhibited a shorter free running period and a decreased response to a phase-delaying light pulse compared with Wistar rats. In several ways these results are similar to those seen in other animal models of depression as well as in depressed humans, suggesting that the WKY rat could be used to investigate the genetic basis for these abnormalities.

Circadian rhythm of acidification in insect vas deferens regulated by rhythmic expression of vacuolar H+-ATPase

2002 ◽  
Vol 205 (1) ◽  
pp. 37-44
Author(s):  
Piotr Bebas ◽  
Bronislaw Cymborowski ◽  
Jadwiga M. Giebultowicz
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Vas Deferens ◽  
Apical Cell ◽  
Transport Processes ◽  
Daily Rhythm ◽  
Constant Darkness ◽  
Cotton Leaf ◽  
Apical Cell Membrane ◽  
Peripheral Tissues

SUMMARY Recent studies have demonstrated that the peripheral tissues of vertebrates and invertebrates contain circadian clocks; however, little is known about their functions and the rhythmic outputs that they generate. To understand clock-controlled rhythms at the cellular level, we investigated a circadian clock located in the reproductive system of a male moth (the cotton leaf worm Spodoptera littoralis) that is essential for the production of fertile spermatozoa. Previous work has demonstrated that spermatozoa are released from the testes in a daily rhythm and are periodically stored in the upper vas deferens (UVD). In this paper, we demonstrate a circadian rhythm in pH in the lumen of the UVD, with acidification occurring during accumulation of spermatozoa in the lumen. The daily rhythm in pH correlates with a rhythmic increase in the expression of a proton pump, the vacuolar H+-ATPase (V-ATPase), in the apical portion of the UVD epithelium. Rhythms in pH and V-ATPase persist in light/dark cycles and constant darkness, but are abolished in constant light, a condition that disrupts clock function and renders spermatozoa infertile. Treatment with colchicine impairs the migration of V-ATPase-positive vesicles to the apical cell membrane and abates the acidification of the UVD lumen. Bafilomycin, a selective inhibitor of V-ATPase activity, also prevents the decline in luminal pH. We conclude that the circadian clock generates a rhythm of luminal acidification by regulating the levels and subcellular distribution of V-ATPase in the UVD epithelium. Our data provide the first evidence for circadian control of V-ATPase, the fundamental enzyme that provides the driving force for numerous secondary transport processes. They also demonstrate how circadian rhythms displayed by individual cells contribute to the synchrony of physiological processes at the organ level.

scholarly journals Effects of chronic caffeine consumption on sleep and the sleep electroencephalogram in mice

2018 ◽  
Vol 33 (1) ◽  
pp. 122-131 ◽  
Author(s):  
Maria Panagiotou ◽  
Mandy Meijer ◽  
Johanna H Meijer ◽  
Tom Deboer
Keyword(s):  
Sleep Deprivation ◽  
Chronic Condition ◽  
Daily Basis ◽  
Light Period ◽  
Caffeine Intake ◽  
Rapid Eye Movement Sleep ◽  
Caffeine Consumption ◽  
Chronic Caffeine ◽  
Circadian Physiology ◽  
The Impact

Background: Caffeine is one of the most widely consumed psychostimulants, and it impacts sleep and circadian physiology. Aim: Caffeine is generally used chronically on a daily basis. Therefore, in the current study, we investigated the chronic effect of caffeine on sleep in mice. Methods: We recorded the electroencephalogram and electromyogram on a control day, on the first day of caffeine consumption (acute), and following two weeks of continuous caffeine consumption (chronic). In the latter condition, a period of six-hour sleep deprivation was conducted during the light period. Control mice, which received normal drinking water, were also recorded and sleep deprived. Results: We found that caffeine induced differential effects following acute and chronic consumption. Over 24 h, waking increased following acute caffeine whereas no changes were found in the chronic condition. The daily amplitude of sleep–wake states increased in both acute and chronic conditions, with the highest amplitude in the chronic condition, showing an increase in sleep during the light and an increase in waking during the dark. Furthermore, electroencephalogram slow-wave-activity in non-rapid eye-movement sleep was increased, compared with both control conditions, during the first half of the light period in the chronic condition. It was particularly challenging to keep the animals awake during the sleep deprivation period under chronic caffeine. Conclusions: Together the data suggest an increased sleep pressure under chronic caffeine. In contrast to the traditional conception on the impact on sleep, chronic caffeine intake seems to increase the daily sleep–wake cycle amplitude and increase sleep pressure in mice.

Zebrafish arylalkylamine-N-acetyltransferase genes – targets for regulation of the circadian clock

2006 ◽  
Vol 36 (2) ◽  
pp. 337-347 ◽  
Author(s):  
L Appelbaum ◽  
D Vallone ◽  
A Anzulovich ◽  
L Ziv ◽  
M Tom ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Pineal Gland ◽  
Circadian Clock ◽  
Fluorescent Protein ◽  
Transgenic Fish ◽  
Constant Darkness ◽  
Rhythmic Expression ◽  
E Box

Daily rhythms of melatonin production are controlled by changes in the activity of arylalkylamine-N-acetyltransferase (AANAT). Zebrafish possess two aanats, aanat1 and aanat2; the former is expressed only in the retina and the latter is expressed in both the retina and the pineal gland. Here, their differential expression and regulation were studied using transcript quantification and transient and stable in vivo and in vitro transfection assays. In the pineal gland, the aanat2 promoter exhibited circadian clock-controlled activity, as indicated by circadian rhythms of Enhanced green fluorescent protein (EGFP) mRNA in AANAT2:EGFP transgenic fish. In vivo transient expression analyses of the aanat2 promoter indicated that E-box and photoreceptor conserved elements (PCE) are required for expression in the pineal gland. In the retina, the expression of both genes was characterized by a robust circadian rhythm of their transcript levels. In constant darkness, the rhythmic expression of retinal aanat2 persisted while the aanat1 rhythm disappeared; indicating that the former is controlled by a circadian clock and the latter is also light driven. In the light-entrainable clock-containing PAC-2 zebrafish cell line, both stably transfected aanat1 and aanat2 promoters exhibited a clock-controlled circadian rhythm, characteristic for an E-box-driven expression. Transient co-transfection experiments in NIH-3T3 cells revealed that the two, E-box- and PCE-containing, promoters are driven by the synergistic action of BMAL/CLOCK and orthehodenticle homeobox 5. This study has revealed a shared mechanism for the regulation of two related genes, yet describes their differential phases and photic responses which may be driven by other gene-specific regulatory mechanisms and tissue-specific transcription factor profiles.

scholarly journals Altered Light Sensitivity of Circadian Clock in Shank3+/– Mouse

2021 ◽  
Vol 15 ◽  
Author(s):  
Javier Alamilla ◽  
Yazmín Ramiro-Cortés ◽  
Adriana Mejía-López ◽  
José-Luis Chavez ◽  
Dulce Olivia Rivera ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Neurodevelopmental Disorder ◽  
Red Light ◽  
Bright Light ◽  
Light Sensitivity ◽  
Autism Spectrum ◽  
Constant Darkness ◽  
Light Pulses ◽  
Immunohistochemical Techniques

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in communication and social interaction, repetitive or stereotypical behaviors, altered sensory perception, and sleep disorders. In general, the causes of ASD remain unknown, but in Phelan–McDermid syndrome, it is known that the disorder is related to the haploinsufficiency of the Shank3 gene. We used an autism model with compromised glutamatergic signaling, the Shank3+/– mouse, to study the circadian rhythm architecture of locomotion behavior and its entrainment to light. We also analyzed the synapse between the retinohypothalamic tract (RHT) and the suprachiasmatic nucleus (SCN), employing tract tracing and immunohistochemical techniques. We found that Shank3+/– mice were not impaired in the SCN circadian clock, as indicated by a lack of differences between groups in the circadian architecture in entrained animals to either long or short photoperiods. Circadian rhythm periodicity (tau) was unaltered between genotypes in constant darkness (DD, dim red light). Similar results were obtained in the re-entrainment to shifts in the light–dark cycle and in the entrainment to a skeleton photoperiod from DD. However, Shank3+/– mice showed larger phase responses to light pulses, both delays and advances, and rhythm disorganization induced by constant bright light. Immunohistochemical analyses indicated no differences in the RHT projection to the SCN or the number of SCN neurons expressing the N-methyl-D-aspartate (NMDA) receptor subunit NR2A, whereas the Shank3+/– animals showed decreased c-Fos induction by brief light pulses at CT14, but increased number of vasoactive intestinal polypeptide (VIP)-positive neurons. These results indicate alterations in light sensitivity in Shank3+/– mice. Further studies are necessary to understand the mechanisms involved in such increased light sensitivity, probably involving VIP neurons.

scholarly journals PER2 Circadian Oscillation Sensitizes Esophageal Cancer Cells to Chemotherapy

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 266
Author(s):  
Juan Alfonso Redondo ◽  
Romain Bibes ◽  
Alizée Vercauteren Drubbel ◽  
Benjamin Dassy ◽  
Xavier Bisteau ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Circadian Rhythm ◽  
Survival Rate ◽  
Circadian Clock ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Response To Therapy ◽  
Circadian Oscillation ◽  
Resistance To Therapy

Esophageal squamous cell carcinoma (eSCC) accounts for more than 85% cases of esophageal cancer worldwide and the 5-year survival rate associated with metastatic eSCC is poor. This low survival rate is the consequence of a complex mechanism of resistance to therapy and tumor relapse. To effectively reduce the mortality rate of this disease, we need to better understand the molecular mechanisms underlying the development of resistance to therapy and translate that knowledge into novel approaches for cancer treatment. The circadian clock orchestrates several physiological processes through the establishment and synchronization of circadian rhythms. Since cancer cells need to fuel rapid proliferation and increased metabolic demands, the escape from circadian rhythm is relevant in tumorigenesis. Although clock related genes may be globally repressed in human eSCC samples, PER2 expression still oscillates in some human eSCC cell lines. However, the consequences of this circadian rhythm are still unclear. In the present study, we confirm that PER2 oscillations still occur in human cancer cells in vitro in spite of a deregulated circadian clock gene expression. Profiling of eSCC cells by RNAseq reveals that when PER2 expression is low, several transcripts related to apoptosis are upregulated. Consistently, treating eSCC cells with cisplatin when PER2 expression is low enhances DNA damage and leads to a higher apoptosis rate. Interestingly, this process is conserved in a mouse model of chemically-induced eSCC ex vivo. These results therefore suggest that response to therapy might be enhanced in esophageal cancers using chronotherapy.

scholarly journals Circadian Rhythm: Potential Therapeutic Target for Atherosclerosis and Thrombosis

2021 ◽  
Vol 22 (2) ◽  
pp. 676
Author(s):  
Andy W. C. Man ◽  
Huige Li ◽  
Ning Xia
Keyword(s):  
Circadian Rhythm ◽  
Cardiovascular Diseases ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Therapeutic Target ◽  
Environmental Changes ◽  
Clock Genes ◽  
Vascular System ◽  
Peripheral Tissues ◽  
Inflammatory Processes

Every organism has an intrinsic biological rhythm that orchestrates biological processes in adjusting to daily environmental changes. Circadian rhythms are maintained by networks of molecular clocks throughout the core and peripheral tissues, including immune cells, blood vessels, and perivascular adipose tissues. Recent findings have suggested strong correlations between the circadian clock and cardiovascular diseases. Desynchronization between the circadian rhythm and body metabolism contributes to the development of cardiovascular diseases including arteriosclerosis and thrombosis. Circadian rhythms are involved in controlling inflammatory processes and metabolisms, which can influence the pathology of arteriosclerosis and thrombosis. Circadian clock genes are critical in maintaining the robust relationship between diurnal variation and the cardiovascular system. The circadian machinery in the vascular system may be a novel therapeutic target for the prevention and treatment of cardiovascular diseases. The research on circadian rhythms in cardiovascular diseases is still progressing. In this review, we briefly summarize recent studies on circadian rhythms and cardiovascular homeostasis, focusing on the circadian control of inflammatory processes and metabolisms. Based on the recent findings, we discuss the potential target molecules for future therapeutic strategies against cardiovascular diseases by targeting the circadian clock.

Are membrane properties essential for the circadian rhythm of Gonyaulax?

1984 ◽  
Vol 247 (2) ◽  
pp. R250-R256
Author(s):  
H. G. Scholubbers ◽  
W. Taylor ◽  
L. Rensing
Keyword(s):  
Circadian Rhythm ◽  
Phase Shift ◽  
Fluorescence Polarization ◽  
The Other ◽  
Membrane Properties ◽  
Response Curves ◽  
Whole Cells ◽  
Different Temperatures ◽  
Free Running ◽  
Free Running Period

Membrane properties of whole cells of Gonyaulax polyedra were measured by fluorescence polarization. Circadian changes of fluorescence polarization exist in exponentially growing cultures. They show an amplitude larger than that of stationary cultures, indicating that a part of the change is due to or amplified by an ongoing cell cycle. Measurements of parameters of the circadian glow rhythm were analyzed for possible correlation with the membrane data. Considerable differences (Q10 = 2.5-3.0) in fluorescence polarization were found in cultures kept at different temperatures ranging from 15 to 27.5 degrees C. The free-running period length at different temperatures, on the other hand, differed only slightly (Q10 = 0.9-1.1). Stationary cultures showed higher fluorescence polarization compared with growing cultures, whereas the free-running period lengths did not differ in cultures of various densities and growth rates. Temperature steps of different sign changed the fluorescence polarization slightly in different directions. The phase shift of 4-h pulses (-5, -9, +7 degrees C) resulted in maximal phase advances of 4, 6, and 2 h, respectively. The phasing of the phase-response curves was identical in all these experiments, a finding not to be expected if the pulses act via the measured membrane properties. Pulses of drugs that change the fluorescence polarization (e.g., chlorpromazine and lidocaine) did not or only slightly phase-shift the circadian rhythm.

Gonadal hormones organize and modulate the circadian system of the rat

1981 ◽  
Vol 241 (1) ◽  
pp. R62-R66 ◽  
Author(s):  
H. E. Albers
Keyword(s):  
Testosterone Propionate ◽  
Wheel Running ◽  
Activity Rhythm ◽  
Gonadal Hormones ◽  
Circadian System ◽  
Female Rats ◽  
Constant Darkness ◽  
Before And After ◽  
Free Running ◽  
Free Running Period

The circadian wheel-running rhythms of gonadectomized adult male, female, and perinatally androgenized female rats, maintained in constant darkness, were examined before and after implantation of Silastic capsules containing cholesterol (C) or estradiol-17 beta (E). The free-running period of the activity rhythm (tau) before capsule implantation tended to be shorter in animals exposed to perinatal androgen. Administration of C did not reliably alter tau in any group. E significantly shortened tau in 100% of females injected with oil on day 3 of life. In females, injected with 3.5 micrograms testosterone propionate on day 3, and males, E shortened or lengthened tau, with the direction and magnitude of this change in tau inversely related to the length of the individual's pretreatment tau. These data indicate that the presence of perinatal androgen does not eliminate the sensitivity of the circadian system of the rat to estrogen, since estrogen alters tau in a manner that depends on its pretreatment length.

Caffeine-Induced Psychosis

CNS Spectrums ◽  
2009 ◽  
Vol 14 (3) ◽  
pp. 127-131 ◽  
Author(s):  
Dawson W. Hedges ◽  
Fu Lye Woon ◽  
Scott P. Hoopes
Keyword(s):  
Antipsychotic Medication ◽  
Healthy People ◽  
Caffeine Intake ◽  
Adenosine Antagonist ◽  
Dopamine Transmission ◽  
Chronic Caffeine ◽  
Chronic Psychosis

ABSTRACTAs a competitive adenosine antagonist, caffeine affects dopamine transmission and has been reported to worsen psychosis in people with schizophrenia and to cause psychosis in otherwise healthy people. We report of case of apparent chronic caffeine-induced psychosis characterized by delusions and paranoia in a 47-year-old man with high caffeine intake. The psychosis resolved within 7 weeks after lowering caffeine intake without use of antipsychotic medication. Clinicians might consider the possibility of caffeinism when evaluating chronic psychosis.

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