Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Biological Clocks”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1999

Photic induction of mPer1 and mPer2 in cry-deficient mice lacking a biological clock.

Mice lacking mCry1 and mCry2 are behaviorally arrhythmic. As shown here, cyclic expression of the clock genes mPer1 and mPer2 (mammalian Period genes 1 and 2) in the suprachiasmatic nucleus and peripheral tissues is abolished and mPer1 and mPer2 mRNA levels are constitutively high. These findings indicate that the biological clock is eliminated in the absence of both mCRY1 and mCRY2 (mammalian cryptochromes 1 and 2) and support the idea that mammalian CRY proteins act in the negative limb of the circadian feedback loop. The mCry double-mutant mice retain the ability to have mPer1 and mPer2 expression induced by a brief light stimulus known to phase-shift the biological clock in wild-type animals. Thus, mCRY1 and mCRY2 are dispensable for light-induced phase shifting of the biological clock.

Animals↗
PubMed2003

The daily rhythm in plasma glucagon concentrations in the rat is modulated by the biological clock and by feeding behavior.

Plasma glucose concentrations display a daily rhythm generated by the hypothalamic biological clock, located in the suprachiasmatic nucleus (SCN). How the SCN orchestrates this rhythm is unknown. Because glucagon stimulates hepatic glucose production, we hypothesized that if glucagon has a daily rhythm, then it may be responsible for the glucose rhythm. From hourly blood samples, we determined daily glucagon concentrations for intact and SCN-lesioned rats. Intact ad libitum-fed rats showed a clear daily glucagon rhythm, and fasting resulted in an even more pronounced rhythm. It is interesting that a decrease in glucagon concentrations, instead of the expected increase, occurred already shortly after food removal. Toward the start of the active period, a peak in glucagon levels occurred, with concentrations similar to those measured in ad libitum-fed rats. SCN lesions abolished rhythmicity in plasma glucagon profiles. Scheduled-fed rats showed meal-induced glucagon peaks but also a daily rhythm in basal premeal glucagon concentrations. Plasma glucose concentrations of ad libitum-and scheduled-fed rats, however, were similar. In conclusion, feeding and the biological clock control 24-h plasma glucagon concentrations. In fed rats, glucagon is not responsible for the daily glucose rhythm. During fasting, however, glucagon may contribute to energy mobilization when the activity period starts.

Animals↗
PubMed1972

Mutants of the biological clock in Chlamydomonas reinhardi.

A genetic analysis of the biological clock in Chlamydomonas reinhardi has been initiated. Of six wild-type strains tested (3 mt(+) and 3 mt(-)), five had periods close to 24 hr whereas one had a 21-hr period. Mutants with altered clock period have been isolated. The periods of 3 of these variant strains are temperature compensated. Genetic crosses involving a long-period mutant suggest that a single gene confers the long-period character, and in general clock-period length seems to be a useful phenotypic measure of alterations in the clock due to genetic differences. One phase mutant was found but its behavior was variable and the phase of the rhythm, relative to a light-dark transition which initiates the rhythm, does not seem to be reliable as a parameter of clock differences. No markers have yet been mapped.

Biological Clocks↗
PubMed1998

Pituitary adenylate cyclase activating peptide (PACAP) in the retinohypothalamic tract: a daytime regulator of the biological clock.

The retinohypothalamic tract (RHT) relays photic information from the eyes to the brain biological clock in the suprachiasmatic nucleus (SCN). Activation of this pathway by light plays a role in adjusting circadian timing to light exposure at night. Here we report a new signaling pathway by which the RHT regulates circadian timing in the daytime as well. Using dual-immunocytochemistry for PACAP and the in vivo tracer Cholera toxin subunit B (ChB), intense PACAP immunoreactivity (PACAP-IR) was observed in retinal afferents at the rat SCN as well as in the intergeniculate leaflet (IGL) of the thalamus. This PACAP-IR was nearly lost upon bilateral eye enucleation. PACAP afferents originated from ganglion cells distributed throughout the retina. The phase of circadian rhythm measured as SCN neuronal activity in vitro was significantly advanced by application of PACAP-38 during the subjective day, but not at night. The effect is channelled to the clock via a PACAP 1 receptor-cAMP signaling mechanism. Thus, in addition to its role in nocturnal regulation by glutamatergic neurotransmission, the RHT can adjust the biological clock by a PACAP-cAMP-dependent mechanism during the daytime.

Animals↗
PubMed2000

GFP fluorescence reports Period 1 circadian gene regulation in the mammalian biological clock.

Endogenous cyclic activation of a specific set of genes, including Period 1 (Per1), drive circadian rhythms in the suprachiasmatic nucleus (SCN), a biological clock nucleus of the brain. We have produced transgenic mice in which a degradable form of recombinant jellyfish green fluorescent protein (GFP) is driven by the mouse Period 1 (mPer1) gene promoter. GFP protein is expressed in the circadian neural structures of the retina and SCN. Fluorescent signals are resolved at the level of individual neurons. mPer1-driven GFP fluorescence intensity reports light-induction and circadian rhythmicity in SCN neurons. This circadian reporter transgene captures the gene expression dynamics of living biological clock neurons and ensembles, providing a novel view of this brain function.

Animals↗
PubMed1990

Steps linking the photosynthetic light reactions to the biological clock require calcium.

The effect of modifying calcium concentration on the expression of the photosynthesis circadian rhythm was examined in Euglena gracilis, Klebs strain Z. Expression of the oxygen evolution rhythm required the presence of both extracellular and intracellular calcium. Several treatments were found to uncouple the rate of the light reactions from the biological clock. In the presence of these chemical agents, the rate of oxygen evolution increased steadily throughout the light portion of the light/dark cycle, instead of showing a peak of activity in the middle of the light cycle. Oxygen evolution was uncoupled from the biological clock when extracellular calcium concentrations were altered by the presence of EGTA or LaCl(3). Uncoupling was also observed when intracellular calcium concentrations were disrupted by the use of Ca(2+) channel blockers, the intracellular Ca(2+) antagonist 8-(diethylamino)-octyl-3,4,5-trimethoxybenzoate, or by disrupting expression of the inositol trisphosphate system. Uncoupling was also observed when the diacylglycerol signaling system, which activates kinase C, was inhibited by acridine orange. The inhibition was reversed by the presence of phorbol esters which activate the kinase. It was concluded that both the inositol trisphosphate and diacylglycerol signaling systems were required for the expression of the oxygen evolution rhythm generated by the biological clock.

Journal Article↗
PubMed1999

[Molecular mechanisms of the biological clock].

Considerable progress has been made in elucidating the mechanisms underlying the generation of circadian rhythmicity. This review describes recent observations and hypothesis on the nature of circadian biological clock in different organisms, such as cyanobacteria (Synechococcus; in which the first noneukaryotic clock was described), Neurospora and Drosophila (representing respectively a fungal and insect system of crucial value for the molecular dissection of circadian timing systems), as well as mammals. Being specific for particular group of organisms, a common model of the circadian biological clock can be depicted which involves a negative transcription/translation-based feedback loop, containing positive and negative elements, and clock genes, as well as clock controlled genes that are directly related to rhythmic metabolism and behavior.

Animals↗
PubMed2004

The biological clock: the bodyguard of temporal homeostasis.

In order for any organism to function properly, it is crucial that it be table to control the timing of its biological functions. An internal biological clock, located, in mammals, in the suprachiasmatic nucleus of the hypothalamus (SCN), therefore carefully guards this temporal homeostasis by delivering its message of time throughout the body. In view of the large variety of body functions (behavioral, physiological, and endocrine) as well as the large variety in their preferred time of main activity along the light:dark cycle, it seems logical to envision different means of time distribution by the SCN. In the present review, we propose that even though it presents a unimodal circadian rhythm of general electrical and metabolic activity, the SCN seems to use several sorts of output connections that are active at different times along the light:dark cycle to control the rhythmic expression of different body functions. Although the SCN is suggested to use diffusion of synchronizing factors in the rhythmic control of behavioral functions, it also needs neuronal connections for the control of endocrine functions. The distribution of the time-of-day message to neuroendocrine systems is either directly onto endocrine neurons or via intermediate neurons located in specific SCN targets. In addition, the SCN uses its connections with the autonomic nervous system for spreading its time-of-day message, either by setting the sensitivity of endocrine glands (i.e., thyroid, adrenal, ovary) or by directly controlling an endocrine output (i.e., melatonin synthesis). Moreover, the SCN seems to use different neurotransmitters released at different times along the light:dark cycle for each of the different connection types presented. Clearly, the temporal homeostasis of endocrine functions results from a diverse set of biological clock outputs.

Animals↗
PubMed2003

Facilitation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor transmission in the suprachiasmatic nucleus by aniracetam enhances photic responses of the biological clock in rodents.

This study was designed to test whether the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor-facilitating drug, aniracetam, could potentiate photic responses of the biological clock in the suprachiasmatic nucleus (SCN) of rodents. Using the whole-cell patch technique, we first demonstrated that AMPA currents elicited by either local AMPA application or optic chiasm stimulation were augmented by aniracetam in the neurons of the SCN. The AMPA application-elicited increase of intracellular Ca2+ concentration in SCN slices was also enhanced by aniracetam treatment. The systemic injection of aniracetam dose-dependently (10-100 mg/kg) potentiated the phase delay in behavioral rhythm induced by brief light exposure of low intensity (3 lux) but not high intensity (10 or 60 lux) during early subjective night. Under the blockade of NMDA receptors by (+) MK801, aniracetam failed to potentiate a light (3 lux)-induced phase delay in behavioral rhythm. Aniracetam increased the photic induction of c-Fos protein in the SCN that was elicited by low intensity light exposure (3 lux). These results suggest that AMPA receptor-mediated responses facilitated by aniracetam can explain enhanced photic responses of the biological clock in the SCN of rodents.

Animals↗
PubMed1994

The pineal organ as a component of the biological clock. Phylogenetic and ontogenetic considerations.

In conclusion, several trends are observed in regard to the phylogenetic development of the pineal organ, which are relevant for our understanding of the evolution of biological clock mechanisms. 1. The pineal organ of all vertebrates investigated thus far is capable of producing and releasing melatonin. Melatonin is rhythmically produced and released during darkness and, thus, represents an important neuroendocrine information on the ambient photoperiod. 2. The rhythmic production of melatonin is under control of endogenous oscillators and photoreceptor cells. In several nonmammalian species, these endogenous oscillators and photoreceptors are located within the pineal organ itself. In some avian species, the inherent rhythmicity of the pineal organ appears to be influenced by pacemakers located in other parts of the central nervous system. Their information may be transmitted to the pineal organ via the sympathetic innervation. This innervation develops progressively in the course of phylogeny. In mammals certain pinealocytes express proteins which are specific of retinal and pineal photoreceptors, but these proteins are obviously not involved in photoreception and phototransduction. The mammalian pineal organ lacks not only functioning photoreceptors, but also endogenous oscillators. The photoreceptor cells involved in regulation of the melatonin biosynthesis are located in the retina; the major endogenous oscillator is the suprachiasmatic nucleus (SCN) of the hypothalamus. Information from the retina and the SCN is transmitted to the mammalian pineal organ via a complex neuronal chain, whose last member is the sympathetic innervation originating from the superior cervical ganglion. This innervation is mandatory to maintain the rhythm of the melatonin biosynthesis in the mammalian pineal organ. Interestingly, the effects of noradrenaline, the major neurotransmitter in the sympathetic nerve fibers, displays opposite effects on the melatonin biosynthesis in birds and mammals: it stimulates the melatonin biosynthesis in the mammalian pineal organ, but inhibits the melatonin formation in the chicken. This conversion occurs at the level of the adrenoreceptors. 3. The intrapineal nerve cells giving rise to pinealofugal neuronal projections are reduced in the course of phylogeny. Nevertheless, direct neuronlike connections appear to exist between the pineal organ and the central nervous system of mammals. These projections originate from a population of pinealocytes. Whether such projections are involved in biological clock mechanisms remains an issue not yet resolved. The ontogenetic data reviewed support the notion that, in lower vertebrates, melatonin biosynthesis is primarily controlled by intrapineal photoreceptors, whereas, in mammals, it depends on retinal photoreceptors and the sympathetic innervation of the pineal.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Putative melatonin receptors in a human biological clock.

In vitro autoradiography with 125I-labeled melatonin was used to examine melatonin binding sites in human hypothalamus. Specific 125I-labeled melatonin binding was localized to the suprachiasmatic nuclei, the site of a putative biological clock, and was not apparent in other hypothalamic regions. Specific 125I-labeled melatonin binding was consistently found in the suprachiasmatic nuclei of hypothalami from adults and fetuses. Densitometric analysis of competition experiments with varying concentrations of melatonin showed monophasic competition curves, with comparable half-maximal inhibition values for the suprachiasmatic nuclei of adults (150 picomolar) and fetuses (110 picomolar). Micromolar concentrations of the melatonin agonist 6-chloromelatonin completely inhibited specific 125I-labeled melatonin binding, whereas the same concentrations of serotonin and norepinephrine caused only a partial reduction in specific binding. The results suggest that putative melatonin receptors are located in a human biological clock.

Autoradiography↗
PubMed2002

Biochemical basis for the biological clock.

NADH oxidases at the external surface of plant and animal cells (ECTO-NOX proteins) exhibit stable and recurring patterns of oscillations with potentially clock-related, entrainable, and temperature-compensated period lengths of 24 min. To determine if ECTO-NOX proteins might represent the ultradian time keepers (pacemakers) of the biological clock, COS cells were transfected with cDNAs encoding tNOX proteins having a period length of 22 min or with C575A or C558A cysteine to alanine replacements having period lengths of 36 or 42 min. Here we demonstrate that such transfectants exhibited 22, 36, or 40 to 42 h circadian patterns in the activity of glyceraldehyde-3-phosphate dehydrogenase, a common clock-regulated protein, in addition to the endogenous 24 h circadian period length. The fact that the expression of a single oscillatory ECTO-NOX protein determines the period length of a circadian biochemical marker (60 X the ECTO-NOX period length) provides compelling evidence that ECTO-NOX proteins are the biochemical ultradian drivers of the cellular biological clock.

Amino Acid Substitution↗
PubMed1997

Resetting the biological clock: mediation of nocturnal CREB phosphorylation via light, glutamate, and nitric oxide.

Synchronization between the environmental lighting cycle and the biological clock in the suprachiasmatic nucleus (SCN) is correlated with phosphorylation of the Ca2+/cAMP response element binding protein (CREB) at the transcriptional activating site Ser133. Mechanisms mediating the formation of phospho-CREB (P-CREB) and their relation to clock resetting are unknown. To address these issues, we probed the signaling pathway between light and P-CREB. Nocturnal light rapidly and transiently induced P-CREB-like immunoreactivity (P-CREB-lir) in the rat SCN. Glutamate (Glu) or nitric oxide (NO) donor administration in vitro also induced P-CREB-lir in SCN neurons only during subjective night. Clock-controlled sensitivity to phase resetting by light. Glu, and NO is similarly restricted to subjective night. The effects of NMDA and nitric oxide synthase (NOS) antagonists on Glu-mediated induction of P-CREB-lir paralleled their inhibition of phase shifting. Significantly, among neurons in which P-CREB-lir was induced by light were NADPH-diaphorase-positive neurons of the SCN's retinorecipient area. Glu treatment increased the intensity of a 43 kDa band recognized by anti-P-CREB antibodies in subjective night but not day, whereas anti-alpha CREB-lir of this band remained constant between night and day. Inhibition of NOS during Glu stimulation diminished the anti-P-CREB-lir of this 43 kDa band. Together, these data couple nocturnal light, Glu, NMDA receptor activation and NO signaling to CREB phosphorylation in the transduction of brief environmental light stimulation of the retina into molecular changes in the SCN resulting in phase resetting of the biological clock.

2-Amino-5-phosphonovalerate↗
PubMed2006

"Diabetes of the elderly" and type 2 diabetes in younger patients: possible role of the biological clock.

The increased prevalence of type 2 diabetes in the aged has been recognized for a long time. Within the last decades, a growing number of younger subjects and even children are prone to develop type 2 diabetes. In both groups, aged and young, the biological clock, located in the suprachiasmatic nucleus of the hypothalamus (SCN) is malfunctioning as evidenced by disturbed sleep cycles and altered circadian rhythms. While elderly patients have an impaired function of the SCN due to the degeneration of neurons, we propose that in younger subjects the clock loses its "feeling" for internal and external rhythms caused by the modern lifestyle. Sleeping late and less coupled with constant metabolic excess alter both internal and external environmental stimuli to the brain. In response to these alterations, the rhythm of the biological clock is disrupted which may lead to the metabolic syndrome and type 2 diabetes.

Adult↗
PubMed2004

Importance of magnesium depletion with hypofunction of the biological clock in the pathophysiology of headhaches with photophobia, sudden infant death and some clinical forms of multiple sclerosis.

Mg depletion is a type of Mg deficit due to a dysregulation of the Mg status. It cannot be corrected through nutritional supplementation only, but requires the most specific correction of the dysregulating mechanism. Among those, Biological Clock (BC) dysrhythmias are to be considered. The aim of this study is to analyze the clinical forms of Mg depletion with hypofunction of the Biological Clock (hBC). hBC may be due to either Primary disorders of BC [Suprachiasmatic Nuclei (SCN) and pineal gland (PG)] or Secondary with homeostatic response [reactive Photophobia (Pphi] to light neurostimulating effects [Nervous Hyper Excitability (NHE)]. The symptomatology is mainly diurnal and observed during fair weather (Spring,Summer). The elective marker of hBC is represented by a decrease in melatonin and in its metabolites in various fluids. The clinical forms of NHE due to Mg depletion with hBC are central and peripheral. The central forms associate anxiety, headaches and dyssomnia. The peripheral manifestations are neuromuscular: photosensitive epilepsia mainly. Three chronopathological forms of Mg depletion with hBC have been highlighted: 1. Headaches with Pphi: mainly migraine; 2. Sudden Infant Death Syndrome (SIDS); 3. Multiple Sclerosis (MS).- Headaches with Pphi, migraine particularly. These cephalalgias are diurnal with Pphi and are aggravated during the fair seasons (particularly during midnight sun-summer). Migraine is their typical form with its dishabituation to visual stimuli and its occipital cortex hyperexcitability. Comorbidity with anxiety is frequent. In 2/3 of the cases, it appears first.- SIDS might be linked to an impaired maturation of both photoendocrine system and brown adipose tissue. MS may be associated with primary disorders of BC Clinical forms of Mg depletion with hBC in MS present diurnal exacerbations and relapses during fair seasons. They have been underestimated because they disagree with the dogma of the << latitude gradient >>, presently questioned. Comorbidities with anxiety and migraine are frequent.hBC may be treated by using darkness therapy with a balanced Mg status. Absolute light deprivation should only be used only in acute indications and is time-limited. Partial substitutive therapy and chromatotherapy have not been validated yet and are still uncertain.

Biological Clocks↗
PubMed1995

Genetic Regulation of Development in Sorghum bicolor (X. Greatly Attenuated Photoperiod Sensitivity in a Phytochrome-Deficient Sorghum Possessing a Biological Clock but Lacking a Red Light-High Irradiance Response).

The role of a light-stable, 123-kD phytochrome in the biological clock, in photoperiodic flowering and shoot growth in extended photoperiods, and in the red light-high irradiance response was studied in Sorghum bicolor using a phytochrome-deficient mutant, 58M (ma3R ma3R), and a near-isogenic wild-type cultivar, 100M (Ma3 Ma3). Since chlorophyll a/b-binding protein mRNA and ribulose bisphosphate carboxylase small subunit mRNA cycled in a circadian fashion in both 58M and 100M grown in constant light, the 123-kD phytochrome absent from 58M does not appear necessary for expression or entrainment of a functional biological clock. Although 58M previously appeared photoperiod insensitive in 12-h photoperiods, extending the photoperiod up to 24 h delayed floral initiation for up to 2 weeks but did not much affect shoot elongation. Thus, although 58M flowers early in intermediate photoperiods, a residual photoperiod sensitivity remains that presumably is not due to the missing 123-kD phytochrome. Since rapid shoot elongation persists in 58M under extended photoperiods despite delayed floral initiation, long photoperiods uncouple those processes. The observed absence of a red light-high irradiance response in 58M, in contrast to the presence of the response in 100M, strengthens the suggestion that the 123-kD phytochrome missing from 58M is a phyB.

Journal Article↗
PubMed2004

Daily variations in type II iodothyronine deiodinase activity in the rat brain as controlled by the biological clock.

Type II deiodinase (D2) plays a key role in regulating thyroid hormone-dependent processes in, among others, the central nervous system (CNS) by accelerating the intracellular conversion of T4 into active T3. Just like the well-known daily rhythm of the hormones of the hypothalamo-pituitary-thyroid axis, D2 activity also appears to show daily variations. However, the mechanisms involved in generating these daily variations, especially in the CNS, are not known. Therefore, we decided to investigate the role the master biological clock, located in the hypothalamus, plays with respect to D2 activity in the rat CNS as well as the role of one of its main hormonal outputs, i.e. plasma corticosterone. D2 activity showed a significant daily rhythm in the pineal and pituitary gland as well as hypothalamic and cortical brain tissue, albeit with a different timing of its acrophase in the different tissues. Ablation of the biological clock abolished the daily variations of D2 activity in all four tissues studied. The main effect of the knockout of the suprachiasmatic nuclei (SCN) was a reduction of nocturnal peak levels in D2 activity. Moreover, contrary to previous observations in SCN-intact animals, in SCN-lesioned animals, the decreased levels of D2 activity are accompanied by decreased plasma levels of the thyroid hormones, suggesting that the SCN separately stimulates D2 activity as well as the hypothalamo-pituitary-thyroid axis.

Adrenal Cortex Hormones↗