Postnatal ontogenesis of the circadian clock within the rat liver

2007 ◽  
Vol 292 (3) ◽  
pp. R1224-R1229 ◽  
Author(s):  
Martin Sládek ◽  
Zuzana Jindráková ◽  
Zdenka Bendová ◽  
Alena Sumová
Keyword(s):  
Circadian Rhythms ◽  
Rat Liver ◽  
Clock Genes ◽  
High Amplitude ◽  
Postnatal Ontogenesis ◽  
Amplitude Variation ◽  
Peripheral Tissues ◽  
Molecular Core ◽  
Peripheral Clocks ◽  
Low Amplitude

In mammals, the circadian oscillator within the suprachiasmatic nuclei (SCN) entrains circadian clocks in numerous peripheral tissues. Central and peripheral clocks share a molecular core clock mechanism governing daily time measurement. In the rat SCN, the molecular clockwork develops gradually during postnatal ontogenesis. The aim of the present work was to elucidate when during ontogenesis the expression of clock genes in the rat liver starts to be rhythmic. Daily profiles of mRNA expression of clock genes Per1, Per2, Cry1, Clock, Rev-Erbα, and Bmal1 were analyzed in the liver of fetuses at embryonic day 20 (E20) or pups at postnatal age 2 (P2), P10, P20, P30, and in adults by real-time RT-PCR. At E20, only a high-amplitude rhythm in Rev-Erbα and a low-amplitude variation in Cry1 but no clear circadian rhythms in expression of other clock genes were detectable. At P2, a high-amplitude rhythm in Rev-Erbα and a low-amplitude variation in Bmal1 but no rhythms in expression of other genes were detected. At P10, significant rhythms only in Per1 and Rev-Erbα expression were present. At P20, clear circadian rhythms in the expression of Per1, Per2, Rev-Erbα, and Bmal1, but not yet of Cry1 and Clock, were detected. At P30, all clock genes were expressed rhythmically. The phase of the rhythms shifted between all studied developmental periods until the adult stage was achieved. The data indicate that the development of the molecular clockwork in the rat liver proceeds gradually and is roughly completed by 30 days after birth.

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.

scholarly journals Modeling and analysis of the impacts of jet lag on circadian rhythm and its role in tumor growth

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4877 ◽  
Author(s):  
Azka Hassan ◽  
Jamil Ahmad ◽  
Hufsah Ashraf ◽  
Amjad Ali
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Clock Genes ◽  
Damage Control ◽  
Vital Role ◽  
Biochemical Networks ◽  
Jet Lag ◽  
Peripheral Tissues ◽  
Modeling And Analysis ◽  
Circadian Clock Proteins

Circadian rhythms maintain a 24 h oscillation pattern in metabolic, physiological and behavioral processes in all living organisms. Circadian rhythms are organized as biochemical networks located in hypothalamus and peripheral tissues. Rhythmicity in the expression of circadian clock genes plays a vital role in regulating the process of cell division and DNA damage control. The oncogenic protein, MYC and the tumor suppressor, p53 are directly influenced by the circadian clock. Jet lag and altered sleep/wake schedules prominently affect the expression of molecular clock genes. This study is focused on developing a Petri net model to analyze the impacts of long term jet lag on the circadian clock and its probable role in tumor progression. The results depict that jet lag disrupts the normal rhythmic behavior and expression of the circadian clock proteins. This disruption leads to persistent expression of MYC and suppressed expression of p53. Thus, it is inferred that jet lag altered circadian clock negatively affects the expressions of cell cycle regulatory genes and contribute in uncontrolled proliferation of tumor cells.

scholarly journals Entrainment of peripheral clock genes by cortisol

2012 ◽  
Vol 44 (11) ◽  
pp. 607-621 ◽  
Author(s):  
Panteleimon D. Mavroudis ◽  
Jeremy D. Scheff ◽  
Steve E. Calvano ◽  
Stephen F. Lowry ◽  
Ioannis P. Androulakis
Keyword(s):  
Clock Genes ◽  
Dynamic Regime ◽  
The Body ◽  
Molecular Function ◽  
Frequency Range ◽  
Peripheral Tissues ◽  
Peripheral Clock ◽  
Peripheral Clocks ◽  
Central Pacemaker ◽  
Peripheral Cells

Circadian rhythmicity in mammals is primarily driven by the suprachiasmatic nucleus (SCN), often called the central pacemaker, which converts the photic information of light and dark cycles into neuronal and hormonal signals in the periphery of the body. Cells of peripheral tissues respond to these centrally mediated cues by adjusting their molecular function to optimize organism performance. Numerous systemic cues orchestrate peripheral rhythmicity, such as feeding, body temperature, the autonomic nervous system, and hormones. We propose a semimechanistic model for the entrainment of peripheral clock genes by cortisol as a representative entrainer of peripheral cells. This model demonstrates the importance of entrainer's characteristics in terms of the synchronization and entrainment of peripheral clock genes, and predicts the loss of intercellular synchrony when cortisol moves out of its homeostatic amplitude and frequency range, as has been observed clinically in chronic stress and cancer. The model also predicts a dynamic regime of entrainment, when cortisol has a slightly decreased amplitude rhythm, where individual clock genes remain relatively synchronized among themselves but are phase shifted in relation to the entrainer. The model illustrates how the loss of communication between the SCN and peripheral tissues could result in desynchronization of peripheral clocks.

scholarly journals Circadian Clock and The Cardiometabolic Risk

2010 ◽  
Vol 2 (2) ◽  
pp. 16
Author(s):  
Anna Meiliana ◽  
Andi Wijaya
Keyword(s):  
Circadian Rhythms ◽  
Cardiometabolic Risk ◽  
Clock Genes ◽  
Epidemiological Data ◽  
Circadian System ◽  
Temporal Organization ◽  
Liver Fat ◽  
Peripheral Tissues ◽  
The Central Nervous System ◽  
Rotation Of The Earth

BACKGROUND: Epidemiological data reveal parallel trends of decreasing sleep duration and increases in metabolic disorders such as obesity, diabetes and hypertension. There is growing evidence that these trends are mechanistically related.CONTENT: The circadian system orchestrates the temporal organization of many aspects of physiology, including metabolism, in synchrony with the 24 hours rotation of the Earth. The circadian system is a complex feedback network that involves interactions between the central nervous system and peripheral tissues. Circadian regulation is intimately linked to metabolic homeostasis and that dysregulation of circadian rhythms can contribute to disease. Conversely, metabolic signals also feed back into the circadian system, modulating circadian gene expression and behavior.SUMMARY: Both inter- and intraorgan desynchrony may be involved in the pathogenesis of cardiometabolic disease attributable to effects in brain and multiple metabolic tissues including heart, liver, fat, muscle, pancreas and gut. Efforts to dissect the molecular mediators that coordinate circadian, metabolic, and cardiovascular systems may ultimately lead to both improved therapeutics and preventive interventions.KEYWORDS: circadian rhythms, clock genes, nuclear receptor, sleep, obesity, cardiometabolic risk

scholarly journals The Angiotensin-Melatonin Axis

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Luciana A. Campos ◽  
Jose Cipolla-Neto ◽  
Fernanda G. Amaral ◽  
Lisete C. Michelini ◽  
Michael Bader ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Metabolic Disorders ◽  
Clock Genes ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Beneficial Effects ◽  
Progression Of Disease ◽  
The Central Nervous System ◽  
Peripheral Clocks

Accumulating evidence indicates that various biological and neuroendocrine circadian rhythms may be disrupted in cardiovascular and metabolic disorders. These circadian alterations may contribute to the progression of disease. Our studies direct to an important role of angiotensin II and melatonin in the modulation of circadian rhythms. The brain renin-angiotensin system (RAS) may modulate melatonin synthesis, a hormone with well-established roles in regulating circadian rhythms. Angiotensin production in the central nervous system may not only influence hypertension but also appears to affect the circadian rhythm of blood pressure. Drugs acting on RAS have been proven effective in the treatment of cardiovascular and metabolic disorders including hypertension and diabetes mellitus (DM). On the other hand, since melatonin is capable of ameliorating metabolic abnormalities in DM and insulin resistance, the beneficial effects of RAS blockade could be improved through combined RAS blocker and melatonin therapy. Contemporary research is evidencing the existence of specific clock genes forming central and peripheral clocks governing circadian rhythms. Further research on the interaction between these two neurohormones and the clock genes governing circadian clocks may progress our understanding on the pathophysiology of disease with possible impact on chronotherapeutic strategies.

scholarly journals Regulation of Melanopsins andPer1byα-MSH and Melatonin in PhotosensitiveXenopus laevisMelanophores

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Maria Nathália de Carvalho Magalhães Moraes ◽  
Luciane Rogéria dos Santos ◽  
Nathana Mezzalira ◽  
Maristela Oliveira Poletini ◽  
Ana Maria de Lauro Castrucci
Keyword(s):  
Gene Expression ◽  
Circadian Rhythms ◽  
Intracellular Signaling ◽  
Cultured Cells ◽  
Clock Genes ◽  
Circadian System ◽  
Time Of Application ◽  
Intracellular Signaling Pathways ◽  
Peripheral Clocks ◽  
Internal Signal

α-MSH and light exert a dispersing effect on pigment granules ofXenopus laevismelanophores; however, the intracellular signaling pathways are different. Melatonin, a hormone that functions as an internal signal of darkness for the organism, has opposite effects, aggregating the melanin granules. Because light functions as an important synchronizing signal for circadian rhythms, we further investigated the effects of both hormones on genes related to the circadian system, namely,Per1(one of the clock genes) and the melanopsins,Opn4xandOpn4m(photopigments).Per1showed temporal oscillations, regardless of the presence of melatonin orα-MSH, which slightly inhibited its expression. Melatonin effects on melanopsins depend on the time of application: if applied in the photophase it dramatically decreasedOpn4xandOpn4mexpressions, and abolished their temporal oscillations, opposite toα-MSH, which increased the melanopsins’ expressions. Our results demonstrate that unlike what has been reported for other peripheral clocks and cultured cells, medium changes or hormones do not play a major role in synchronizing theXenopusmelanophore population. This difference is probably due to the fact thatX. laevismelanophores possess functional photopigments (melanopsins) that enable these cells to primarily respond to light, which triggers melanin dispersion and modulates gene expression.

scholarly journals Differential impacts of the head onPlatynereis dumeriliiperipheral circadian rhythms

2019 ◽  
Author(s):  
Enrique Arboleda ◽  
Martin Zurl ◽  
Kristin Tessmar-Raible
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Clock Genes ◽  
Functional Model ◽  
Circadian Clocks ◽  
Constant Darkness ◽  
Dark Cycle ◽  
Peripheral Tissues ◽  
Platynereis Dumerilii ◽  
Strong Control

AbstractBackgroundThe marine bristle wormPlatynereis dumeriliiis a useful functional model system for the study of the circadian clock and its interplay with others, e.g. circalunar clocks. The focus has so far been on the worm’s head. However, behavioral and physiological cycles in other animals typically arise from the coordination of circadian clocks located in the brain and in peripheral tissues. Here we focus on peripheral circadian rhythms and clocks, revisit and expand classical circadian work on the worm’s chromatophores, investigate locomotion as read-out and include molecular analyses.ResultsWe establish that different pieces of the trunk exhibit synchronized, robust oscillations of core circadian clock genes. These circadian core clock transcripts are under strong control of the light-dark cycle, quickly losing synchronized oscillation under constant darkness, irrespective of the absence or presence of heads. Different wavelengths are differently effective in controlling the peripheral molecular synchronization. We have previously shown that locomotor activity is under circadian clock control. Here we show that upon decapitation it still follows the light-dark cycle, but does not free-run under constant darkness. We also observe the rhythmicity of pigments in the worm’s individual chromatophores, confirming that chromatophore size changes follow a circadian pattern. These size changes continue under constant darkness, but cannot be re-entrained by light upon decapitation.ConclusionsHere we provide the first basic characterization of the peripheral circadian clock ofPlatynereis dumerilii. In the absence of the head, light is essential as a major synchronization cue for peripheral molecular and locomotor circadian rhythms. Circadian changes in chromatophore size can however continue for several days in the absence of light/dark changes and the head. Thus, the dependence on the head depends on the type of peripheral rhythm studied. These data show that peripheral circadian rhythms and clocks should be considered when investigating the interactions of clocks with different period lengths, a notion likely also true for other organisms with circadian and non-circadian clocks.

scholarly journals Circadian Rhythm Variations and Nutrition in Children

2018 ◽  
Vol 08 (01) ◽  
pp. e60-e66 ◽  
Author(s):  
Marie Gombert ◽  
Joaquín Carrasco-Luna ◽  
Gonzalo Pin-Arboledas ◽  
Pilar Codoñer-Franch
Keyword(s):  
Circadian Rhythms ◽  
Metabolic Diseases ◽  
Clock Genes ◽  
Light Exposure ◽  
Daily Basis ◽  
Biological Processes ◽  
Life Habits ◽  
Peripheral Clocks ◽  
Opposite Situation ◽  
Central Clock

AbstractCircadian rhythms are the changes in biological processes that occur on a daily basis. Among these processes are reactions involved in metabolic homeostasis. Circadian rhythms are structured by the central clock in the suprachiasmatic nucleus of the hypothalamus via the control of melatonin expression. Circadian rhythms are also controlled by the peripheral clocks, which are intracellular mechanisms composed of the clock genes, whose expression follows a circadian pattern. Circadian rhythms are impacted by signals from the environment called zeitgebers, or time givers, which include light exposure, feeding schedule and composition, sleeping schedule and pattern, temperature, and physical exercise. When the signals from the environment are synchronized with the internal clocks, metabolism is optimized. The term chronodisruption is used to describe the opposite situation. The latest research has demonstrated that life habits coherent with the internal clocks should be adopted, especially during childhood, to prevent metabolic diseases. Nevertheless, a few studies have investigated this link in children, and key information remains unknown.

scholarly journals Impact of Short-Term Fasting on The Rhythmic Expression of the Core Circadian Clock and Clock-Controlled Genes in Skeletal Muscle of Crucian Carp (Carassius auratus)

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 526 ◽  
Author(s):  
Ping Wu ◽  
Lingsheng Bao ◽  
Ruiyong Zhang ◽  
Yulong Li ◽  
Li Liu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Circadian Rhythms ◽  
Crucian Carp ◽  
Clock Genes ◽  
Functional Genes ◽  
Short Term ◽  
Peripheral Tissues ◽  
Circadian Genes ◽  
Rhythmic Expression ◽  
The Core

The peripheral tissue pacemaker is responsive to light and other zeitgebers, especially food availability. Generally, the pacemaker can be reset and entrained independently of the central circadian structures. Studies involving clock-gene expressional patterns in fish peripheral tissues have attracted considerable attention. However, the rhythmic expression of clock genes in skeletal muscle has only scarcely been investigated. The present study was designed to investigate the core clock and functional gene expression rhythms in crucian carp. Meanwhile, the synchronized effect of food restrictions (short-term fasting) on these rhythms in skeletal muscle was carefully examined. In fed crucian carp, three core clock genes (Clock, Bmal1a, and Per1) and five functional genes (Epo, Fas, IGF1R2, Jnk1, and MyoG) showed circadian rhythms. By comparison, four core clock genes (Clock, Bmal1a, Cry3, and Per2) and six functional genes (Epo, GH, IGF2, Mstn, Pnp5a, and Ucp1) showed circadian rhythms in crucian carp muscle after 7-day fasting. In addition, three core clock genes (Clock, Per1, and Per3) and six functional genes (Ampk1a, Lpl, MyoG, Pnp5a, PPARα, and Ucp1) showed circadian rhythms in crucian carp muscle after 15-day fasting. However, all gene rhythmic expression patterns differed from each other. Furthermore, it was found that the circadian genes could be altered by feed deprivation in crucian carp muscle through the rhythms correlation analysis of the circadian genes and functional genes. Hence, food-anticipatory activity of fish could be adjusted through the food delivery restriction under a light–dark cycle. These results provide a potential application in promoting fish growth by adjusting feeding conditions and nutritional state.

scholarly journals Circadian rhythms in bipolar disorder patient-derived neurons predict lithium response

2020 ◽  
Author(s):  
Himanshu K Mishra ◽  
Noelle M. Ying ◽  
Angelica Luis ◽  
Heather Wei ◽  
Metta Nguyen ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Clock Genes ◽  
Single Cells ◽  
Neuronal Precursor Cells ◽  
Disorder Patient ◽  
Induced Pluripotent ◽  
And Control ◽  
Low Amplitude

Bipolar disorder (BD) is a neuropsychiatric disorder with genetic risk factors defined by recurrent episodes of mania/hypomania, depression and circadian rhythm abnormalities. While lithium is an effective drug for BD, 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, rhythm abnormalities in BD have not been evaluated in neurons and it is unknown if neuronal rhythms differ between Li-R and Li-NR. We used induced pluripotent stem cells (iPSCs) to culture neuronal precursor cells (NPC) and glutamatergic neurons from BD patients and controls. We identified strong circadian rhythms in Per2-luc expression in NPCs and neurons from controls and Li-R. 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 expression was 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.

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