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Chromosoma Aug 2007For life forms to survive, they must adapt to their environmental conditions. One such factor that impacts on both prokaryotic and eukaryotic organisms is the light-dark... (Review)
Review
For life forms to survive, they must adapt to their environmental conditions. One such factor that impacts on both prokaryotic and eukaryotic organisms is the light-dark cycle, a consequence of planetary rotation in relation to our sun. In mammals, the daily light cycle has affected the regulation of many cellular processes such as sleep-wake and calorific intake activities, hormone secretion, blood pressure and immune system responses. Such rhythmic behaviour is the consequence of circadian rhythm/biological clock (BC) systems which are controlled in a light stimulus-dependent manner by a master clock called the suprachiasmatic nucleus (SCN) situated within the anterior hypothalamus. Peripheral clocks located in other organs such as the liver and kidneys relay signals from the SCN, which ultimately leads to tightly controlled expression of several protein families that in turn act on a broad range of cellular functions. Work in lower organisms has demonstrated a link between aging processes and BC factors, and studies in both animal models and clinical trials have postulated a role for certain BC-associated proteins in tumourigenesis and cancer progression. Recent exciting data reported within the last year or so have now established a molecular link between specific BC proteins and factors that control the mammalian cell cycle and DNA damage checkpoints. This mini review will focus on these discoveries and emphasise how such BC proteins may be involved, through their interplay with cell cycle/DNA damage response pathways, in the development of human disease such as cancer.
Topics: Animals; Biological Clocks; Cell Cycle; Checkpoint Kinase 1; Circadian Rhythm; DNA Damage; DNA Repair; Genes, cdc; Humans; Light; Protein Kinases; Protein Serine-Threonine Kinases; Protein-Tyrosine Kinases; Suprachiasmatic Nucleus
PubMed: 17492458
DOI: 10.1007/s00412-007-0108-6 -
Nihon Shinkei Seishin Yakurigaku Zasshi... Jun 2007Mammalians circadian pacemaker resides in the paired suprachiasmatic nuclei (SCN). Clock genes are the genes that control the circadian rhythms in physiology and... (Review)
Review
Mammalians circadian pacemaker resides in the paired suprachiasmatic nuclei (SCN). Clock genes are the genes that control the circadian rhythms in physiology and behavior. The effectiveness and toxicity of many drugs vary depending on dosing time associated with 24-hr rhythms of biochemical, physiological and behavioral processes under the control of the circadian clock. However, many drugs are still given without regard to the time of day. Identification of a rhythmic marker for selecting dosing time will lead to advanced chronopharmacotherapy. To monitor the rhythmic marker may be useful to choose the most appropriate time of day for administration of drugs that may increase their therapeutic effects and/or reduce their side effects. On the other hand, several drugs can cause alterations to the 24-hr rhythms, which leads to illness and altered homeostatic regulation. Furthermore, to produce new rhythmicity by manipulating the conditions of living organs by using rhythmic administration of altered feeding schedules or several drugs appears to lead to the new concept of chronopharmacotherapy. One approach to increasing the efficiency of pharmacotherapy is administering drugs at times during which they are best effective and/or tolerated.
Topics: Animals; Biological Clocks; Chronotherapy; Circadian Rhythm; Drug Delivery Systems; Humans; Pharmaceutical Preparations; Pharmacokinetics; Suprachiasmatic Nucleus
PubMed: 17633520
DOI: No ID Found -
PLoS Computational Biology Jun 2022The biological master clock, suprachiasmatic nucleus (of rat and mouse), is composed of ~10,000 clock cells which are heterogeneous with respect to their circadian...
The biological master clock, suprachiasmatic nucleus (of rat and mouse), is composed of ~10,000 clock cells which are heterogeneous with respect to their circadian periods. Despite this inhomogeneity, an intact SCN maintains a very good degree of circadian phase (time) coherence which is vital for sustaining various circadian rhythmic activities, and it is supposedly achieved by not just one but a few different cell-to-cell coupling mechanisms, among which action potential (AP)-mediated connectivity is known to be essential. But, due to technical difficulties and limitations in experiments, so far very little information is available about the morphology of the connectivity at a cellular scale. Building upon this limited amount of information, here we exhaustively and systematically explore a large pool (~25,000) of various network morphologies to come up with some plausible network features of SCN networks. All candidates under consideration reflect an experimentally obtained 'indegree distribution' as well as a 'physical range distribution of afferent clock cells.' Then, importantly, with a set of multitude criteria based on the properties of SCN circadian phase waves in extrinsically perturbed as well as in their natural states, we select out appropriate model networks: Some important measures are, 1) level of phase dispersal and direction of wave propagation, 2) phase-resetting ability of the model networks subject to external circadian forcing, and 3) decay rate of perturbation induced "phase-singularities." The successful, realistic networks have several common features: 1) "indegree" and "outdegree" should have a positive correlation; 2) the cells in the SCN ventrolateral region (core) have a much larger total degree than that of the dorsal medial region (shell); 3) The number of intra-core edges is about 7.5 times that of intra-shell edges; and 4) the distance probability density function for the afferent connections fits well to a beta function. We believe that these newly identified network features would be a useful guide for future explorations on the very much unknown AP-mediated clock cell connectome within the SCN.
Topics: Action Potentials; Animals; Biological Clocks; Circadian Clocks; Circadian Rhythm; Connectome; Mice; Rats; Suprachiasmatic Nucleus
PubMed: 35666776
DOI: 10.1371/journal.pcbi.1010213 -
Magnesium Research Dec 2002The main mechanisms of the chronopathological forms of magnesium depletion associate a low Mg intake with various dysregulating biorhythms. The differentiation between... (Review)
Review
The main mechanisms of the chronopathological forms of magnesium depletion associate a low Mg intake with various dysregulating biorhythms. The differentiation between forms with hyperfunction and forms with hypofunction of the biological clock is seminal and the main marker is the production of melatonin (MT). The clinical forms of the various patterns of the chronopathological forms of Mg depletion may be central or peripheral. The clinical forms with hyperfunction of the biological clock (marker: increase in MT) may associate diverse expressions of nervous hypoexcitability: depression (i.e. Seasonal affective disease); cephalalgias nocturnal, without photophobia (i.e. cluster headaches); dyssomnia LASPS (advanced sleep phase syndrome) particularly]; asthenia and myalgias (i.e. fibromyalgia, chronic fatigue syndrome). The main comorbidity is found with depressive states. The therapy relies on classical bright light phototherapy, sometimes associated with psychoanaleptics. The clinical forms with hypofunction of biological clock (marker: decrease in MT) may associate various signs of nervous hyperexcitability (HEN): anxiety (from generalized anxiety to panic attacks); cephalalgias diurnal with photophobia (mainly migraine); dyssomnia [DSPS (delayed sleep phase syndrome) particularly, jet lag, night work disorders, age related insomnia, sometimes with inappropriate behaviour; photogenic epilepsia, generalized or focal; some clinical forms of chronic fatigue syndrome and fibromyalgia. The main comorbidity is between migraine and epilepsia. The treatment relies on the diverse forms of darkness therapy, possibly with the help of some psycholeptics: anxiolytics and anticonvulsants. The indications of chromatotherapy remain to be validated.
Topics: Animals; Biological Clocks; Humans; Magnesium; Magnesium Deficiency; Seasonal Affective Disorder
PubMed: 12635882
DOI: No ID Found -
Hypertension Research : Official... Jul 2010Cardiovascular functions, including blood pressure and vascular functions, show diurnal oscillation. Circadian variations have been clearly shown in the occurrence of... (Review)
Review
Cardiovascular functions, including blood pressure and vascular functions, show diurnal oscillation. Circadian variations have been clearly shown in the occurrence of cardiovascular events such as acute myocardial infarction. Circadian rhythm strongly influences human biology and pathology. The identification and characterization of mammalian clock genes revealed that they are expressed almost everywhere throughout the body in a circadian manner. In contrast to the central clock in the suprachiasmatic nucleus (SCN), the clock in each tissue or cell is designated as a peripheral clock. It is now accepted that peripheral clocks have their own roles specific to each peripheral organ by regulating the expression of clock-controlled genes (CCGs), although the oscillation mechanisms of the peripheral clock are similar to that of the SCN. However, little was known about how the peripheral clock in the vasculature contributes to the process of cardiovascular disorders. The biological clock allows each organ or cell to anticipate and prepare for changes in external stimuli. Recent evidence obtained using genetically engineered mice with disrupted circadian rhythm showed a novel function of the internal clock in the pathogenesis of endothelial dysfunction, hypertension and hemostasis. Loss of synchronization between the central and peripheral clock also contributes to the pathogenesis of cardiovascular diseases, as restoration of clock homeostasis could prevent disease progression. Identification of CCGs in each organ, as well as discovery of tools to manipulate the phase of each biological clock, will be of great help in establishing a novel chronotherapeutic approach to the prevention and treatment of cardiovascular disorders.
Topics: Animals; Biological Clocks; Blood Pressure; Cardiovascular Diseases; Circadian Rhythm; Cricetinae; Hemostasis; Humans; Hypertension; Mice; Suprachiasmatic Nucleus; Thrombosis
PubMed: 20448639
DOI: 10.1038/hr.2010.68 -
Irish Medical Journal Jun 2015
Topics: Biological Clocks; Female; Fertility Preservation; Humans; Ireland; Male; Oocyte Retrieval
PubMed: 26182796
DOI: No ID Found -
Drug Metabolism and Pharmacokinetics Feb 2007The mammalians circadian pacemaker resides in the paired suprachiasmatic nuclei (SCN) and influences a multitude of biological processes, including the sleep-wake...
The mammalians circadian pacemaker resides in the paired suprachiasmatic nuclei (SCN) and influences a multitude of biological processes, including the sleep-wake rhythm. Clock genes are the genes that control the circadian rhythms in physiology and behavior. The effectiveness and toxicity of many drugs vary depending on dosing time associated with 24 hr rhythms of biochemical, physiological and behavioral processes under the control of circadian clock. Such chronopharmacological phenomena are influenced by not only the pharmacokinetics but also pharmacodynamics of medications. Identification of a rhythmic marker for selecting dosing time will lead to improved progress and diffusion of chronopharmacotherapy. The mechanisms underlying chronopharmacological findings should be clarified from the viewpoint of clock genes. On the other hand, several drugs have an effect on circadian clock. The knowledge of interactions between circadian clock and drugs should be very useful for clinical practice. Therefore, I introduce the regulatory system of biological rhythm from viewpoints of clock genes and the possibility of pharmacotherapy based on clock genes.
Topics: Animals; Biological Clocks; Drug Therapy; Environment; Humans; Pharmacokinetics; Pharmacology
PubMed: 17329905
DOI: 10.2133/dmpk.22.3 -
Cell and Tissue Research Jul 2002Mechanisms underlying circadian clock function in Drosophila melanogaster have been revealed by genetic and molecular approaches. Two interlocked transcriptional... (Review)
Review
Mechanisms underlying circadian clock function in Drosophila melanogaster have been revealed by genetic and molecular approaches. Two interlocked transcriptional feedback loops involving at least the period, timeless, Clock,and cycle genes generate molecular oscillations that are believed to control behavioral rhythmicity and other clock outputs. These oscillations are further enhanced and fine-tuned to match the duration of the solar day by post-transcriptional and post-translational mechanisms depending on the PERIOD and TIMELESS proteins and on the protein kinases DOUBLE-TIME and SHAGGY. Light is the principal zeitgeber for synchronizing molecular and behavioral rhythmicity via the blue-light photoreceptor CRYPTOCHROME and the TIMELESS protein. In addition, light seems required for maintaining robust molecular oscillations at least in peripheral clock-gene-expressing tissues like the eyes, antennae, or Malpighian tubules. Relaying temporal information to cells and tissues expressing overt biological rhythms involves regulation of "output genes" at multiple levels. Although their regulation depends on the major clock genes, the majority of the clock-controlled genes are not direct targets of clock factors.
Topics: Animals; Biological Clocks; Drosophila
PubMed: 12111533
DOI: 10.1007/s00441-002-0569-0 -
Advanced Drug Delivery Reviews Jul 2010
Topics: Animals; Circadian Clocks; Circadian Rhythm; Drug Chronotherapy; Drug Delivery Systems; Humans; Pharmaceutical Preparations
PubMed: 20553776
DOI: 10.1016/j.addr.2010.05.007 -
Cell Aug 1994
Review
Topics: Animals; Biological Clocks; Circadian Rhythm; Gene Expression Regulation; Hypothalamus; Periodicity; Seasons; Transcription, Genetic
PubMed: 8062383
DOI: 10.1016/0092-8674(94)90415-4