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At least 433 records · Page 24Linked to original sources
PubMed2005

Computational model of an adaptive rhythm generator within the olivocerebellar system.

The aim of this study is to investigate via computation whether the olivocerebellar system is capable of functioning as an adaptive rhythm generator. For this purpose, a detailed and physiologically realistic computational model of the olivocerebellar system is developed, based on the known intrinsic cell and network topological properties of this brain system. The present network, where individual cells are modelled by leaky integrate-and-fire units, converts the irregular spikes produced by the olivary cells into a precise rhythmic signal at the output. The simulation results reveal that the computational model, which normally does not exhibit any rhythmic activity, could be switched into a new mode in which it functions as a rhythm generator producing pulses within three different frequency ranges corresponding to alpha, beta, or gamma bands, respectively. In either mode of operation, the firing rates of all simulated cell types are observed to match real data. The results of this study therefore support the experimental findings of researchers who argue that a biological clock producing rhythmic pulses within different temporal ranges is located within the cerebellum.

Action Potentials↗
PubMed1976

Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat.

Sequential blood samples were obtained from undisturbed freely-behaving male rats bearing chronic intracardiac venous cannulae. Blood was withdrawn every 15 min for periods of 4-24 h; plasma was separated, and saline-resuspended red cells were reinjected. Plasma GH was determined by radioimmunoassay. Pulsatile GH secretion was evident in each animal with most peak values greater than 200 ng/ml and most trough values less than ng/ml. The GH secretory episodes occurred at approximately 3 h intervals, and this rhythmic pattern of GH secretion persisted unchanged across all phases of a 12-h light-dark (L-D) cycle. Seven major episodes of GH secretion were observed during a single 24-h period. The mean period, or time interval between episodes, in 24 animals was 3.32 +/- 0.07 (SEM)h. The timing of the pulses with respect to the L-D cycle was similar in most animals, indicating that the rhythm may be entrained to the L-D cycle. The role of environmental lighting was further assessed in 14 animals exposed to constant light for 7 weeks. The results show that the basic rhythm was unchanged (mean period 3.18 +/- 0.06 h, peaks greater than 200 ng/ml, troughs less than 1 ng/ml), although entrainment to time of day was not evident. Subsequent exposure to the 12-h L-D cycle resulted in reversion to an entrained rhythm. These results suggest 1) that GH secretion in the rat is governed by an endogenous ultradian rhythm, with a periodicity of approximately 3.3 h, and 2) that the alternation of light and darkness probably serves as a Zeitgeber which sets the biological "clock" for GH secretion, but is not necessary for maintenance of the basic rhythm.

Animals↗
PubMed1976

Light, behavior, and biologic rhythms.

The most potent environmental synchronizer of "biologic clocks" in mammals is the light-dark cycle. The author describes experiments that identify a particular pathway--a derect connection between retina and hypothalamus--as the main route by which such biologic rhythms as the daily activity cycle, the estrous cycle, and the annual reproductive cycle are entrained to the external environment.

Animals↗
PubMed1979

Seasonality in biochemical determinations: a source of variance and a clue to the temporal incidence of affective illness.

Systematic investigation of seasonal variations revealed unimodal annual rhythms in platelet serotonin uptake and DBH activity, bimodal seasonal rhythms in free and total tryptophan, melatonin, and platelet serotonin, and significant fluctuations of higher frequency in platelet MAO activity and protein. The methodological importance of seasonality is emphasized by the fact that the seasonal changes noted were often greater than differences previously found in the same parameters between depressive patients and controls. Since seasonal rhythms are circadian in origin, impairment of a central 24-hour biological clock could provide a common basis for circadian rhythm disturbances and seasonality in affective disorders.

Adult↗
PubMed1993

Chronobiology: neural pacemakers of biological rhythms.

Biological rhythms are ubiquitous being demonstrable of any level of organization in living matter. However, the myriad of biological oscillators in peripheral organs are organized and synchronized by special structure, i.e., biological clocks, mostly located in central nervous system. Neural pacemakers show intrinsic properties which are illustrated and discussed. Understanding the meaning and function of neural oscillators is fundamental for those who wants to know how the biological structure of time is processed in living systems.

Animals↗
PubMed1977

Oscillatory chemical reactions: the Tomita-Kitahara model.

Biological clocks share with excitable membrane (nerve, muscle) the requirement that the chemical systems that underlie them have unstable steady states, and hence are capable of limit-cycle oscillations. A particularly simple model of a chemical oscillator is discussed, especially with reference to the reverse reaction, which tends to damp the oscillations. For thermodynamic reasons (entropy production) reversibility can not, however, be neglected. The steady state, even when stable, does not minimize the dissipation function. Computer studies show the response to sinusoidal variation of the rate constant governing the autocatalytic step.

Animals↗
PubMed2005

Seasonal variation of the impact of a stressful procedure on open field behaviour and blood corticosterone in laboratory mice.

Behavioural and hormonal seasonal changes are well documented in various vertebrate species living in their natural environment but circannual variations that may occur in laboratory animals reared in standard conditions are poorly investigated. This study shows that, in laboratory mice, the effects of stress on behavioural inhibition, investigatory behaviour and blood concentration of corticosterone are seasonally dependent. No consistency was observed between the reactivity of biological structures controlling the hormonal response to stress and the behavioural activities investigated at every period of the year. During the spring time, stress, which elicited a decrease of investigatory behaviour (estimated by the walking time in an open field), increased behavioural inhibition (estimated by the percentage of walking in the central area of the open field) as well as the blood corticosterone concentration in laboratory mice. In autumn, stress had no significant effect on behaviour despite the great hormonal concentration increase. The results reveal that, at certain period of the year, a stressful procedure is unable to affect behavioural parameters in laboratory mice which were maintained in constant 12-h dark/12-h light cycle. The report constitutes a novel piece of information suggesting a potential role of the endogenous biological clock in the modulation of stress response in mammals.

Analysis of Variance↗
PubMed1998

Melatonin-responsive headache in delayed sleep phase syndrome: preliminary observations.

The occurrence of headache and its change after treatment with melatonin 5 mg were studied in 30 patients with delayed sleep phase syndrome. The medication was taken 5 hours before the endogenous nocturnal plasma melatonin concentration had reached 10 pg/mL. Three women (aged 14, 14, and 23 years) suffered from chronic tension-type headache. Their headache disappeared within 2 weeks after the start of treatment with melatonin. One 54-year-old man suffered from disabling migraine attacks without aura, twice a week. After starting melatonin treatment, only three migraine attacks were reported in 12 months. Ever since his 40s, a 60-year-old man complained of cluster headache episodes lasting about 2 months, twice a year. In the year since starting melatonin treatment, only one 5-day cluster episode occurred. Nocturnal melatonin secretion in the patients with delayed sleep phase syndrome and headache did not differ significantly from that in the patients with the sleep disorder but without headache. Melatonin may be helpful in patients with headache who are suffering from delayed sleep phase syndrome. Its effectiveness may be due to modification of vascular and nociceptive systems or to its chronobiological action which adjusts the patient's biological clock to his/her life-style.

Adolescent↗
PubMed2005

The human circadian system in normal and disordered sleep.

The human circadian system regulates rhythmicity in the human body and establishes normal sleep and wake phases. The suprachiasmatic nuclei (SCN), located in the hypothalamus above the optic chiasm, make up the human pacemaker known as the circadian or biological clock, but other essential parts of the circadian system include the pineal gland, retina, and retinohypothalamic tract. The importance of light in resetting the intrinsic human circadian cycle, the intrinsic period of which is slightly longer than 24 hours, ensures that the human cycle will stay entrained to the earth's 24-hour daily cycle. Within the SCN neurons, circadian rhythmicity is generated by the regular transcription of proteins. Since the circadian system is the foundation of the sleep-wake cycle, disorders and abnormalities in sleep are often connected with disorders or abnormalities in the circadian system. Circadian rhythm sleep disorders, such as jet lag syndrome and shift work sleep disorder, are those specifically attributed to dysfunctions or insufficiencies in the circadian system. Taking into consideration the preeminence of the circadian clock in timing sleep, it is likely that other sleep disorders, such as insomnia, are also linked to circadian system abnormalities.

Biological Clocks↗
PubMed1994

Circadian clock locus frequency: protein encoded by a single open reading frame defines period length and temperature compensation.

The frequency (frq) locus encodes a key component, a state variable, in a cellular oscillator generating circadian rhythmicity. Two transcripts have been mapped to this region, and data presented here are consistent with the existence of a third transcript. Analysis of cDNA clones and clock mutants from this region focuses attention on one transcript encoding a protein. FRQ, which is a central clock component: (i) mutations in all of the semidominant frq alleles are the result of single amino acid substitutions and map to the open reading frame (ORF) encoding FRQ; (ii) deletion of this ORF, or a frameshift mutation within it, results in a strain with a recessive clock phenotype characterized by the loss of rhythm stability and compensation. Single amino acid substitutions within, or disruption of, this single ORF are thus sufficient to drive major alterations in both period length and temperature compensation, two canonical characteristics of circadian systems. The 989-amino acid FRQ protein species the circadian function of frq in the assembly of the Neurospora biological clock.

Alleles↗
PubMed2000

The rat arylalkylamine N-acetyltransferase E-box: differential use in a master vs. a slave oscillator.

The rat arylalkylamine N-acetyltransferase (AA-NAT) gene encodes the key enzyme whose rhythmic expression drives the nocturnal production of melatonin. It is of interest that this enzyme is expressed virtually exclusively in two phylogenetically related tissues: retinal photoreceptors, which harbor an endogenous clock, and pinealocytes which, in higher vertebrates, function strictly in response to the master oscillator in the suprachiasmatic nucleus (SCN). While much is known about AA-NAT transcriptional regulation in the rat pineal gland (a slave oscillator), a full understanding of the mechanisms controlling AA-NAT gene expression in the retina by the clock is lacking. In the present study we have identified a functional E box in the first intron of the rat AA-NAT gene which is capable of mediating transcriptional upregulation via the action of a bMAL/CLOCK heterodimer. This is the first report to characterize the AA-NAT gene as a possible direct transcriptional target of the biological clock loop in a master oscillator.

Animals↗
PubMed1999

Acute and chronic effects of toxic metals on viability, encystment and bioluminescence in the dinoflagellate Gonyaulax polyedra.

Toxicity bioassays based on survival were carried out with cells of the marine dinoflagellate Gonyaulax polyedra exposed to mercury (Hg2+ ), cadmium (Cd2+), lead (Pb2+) and copper (Cu2+). The toxicity scale of these metals found was Hg2+ > Cu2+ > Cd2+ > Pb2+. Cells exposed to metals promptly underwent encystment, which is an important strategy for surviving metal exposure. Following 48 h exposure to Cu2+, complete excystment occurred within 96 h after reinoculation of cells in fresh metal-free media, and with Pb2+ partial recovery occurred in that time. Bioluminescence was affected by the metals in a dose-dependent manner primarily by increasing the frequency of flashing, but the glow emission was also altered with acute Cu2+ and Pb2+ treatments. Several physiological processes in G. polyedra are under circadian control. Chronic exposures to metals caused no substantial alterations in the circadian rhythm of bioluminescence glow, indicating that the biological clock of this dinoflagellate is not sensitive to these metals at the concentrations tested.

Animals↗
PubMed2005

The pineal aging and death program: life prolongation in pre-aging pinealectomized mice.

A precise temporal program for growth, fertility, aging, and death exists in the "pineal complex" of the brain. It tracks, like a "clock," the ontogenetic phases of our life program. Transplantation of a very old pineal gland into the thymus or under the kidney capsule of a young mouse produces acceleration of aging and early death. We investigated the existence of such an inner biological clock on the assumption that a time exists in the pineal program when the pineal gland actively starts to deliver aging and death "signals" to the body, thus accomplishing its genetically inscribed sequence. Groups of BALB/c male or female mice were surgically pinealectomized (PX) at the age of 3, 5, 7, 9, 14, and 18 months, and their life span was evaluated. Periodical measurements of blood and hormonal and metabolic parameters were taken. Results showed that while PX at the age of 3 and 5 months promotes acceleration of aging, no relevant effect of PX is observed in mice PX at 7 or 9 months of age. On the contrary, a remarkable life prolongation was observed when mice were PX at the age of 14 months. No effects were seen when the mice were PX at 18 months of age. The same aging-promoting or -delaying effects were confirmed in the hematological and hormonal-metabolic values measured. The findings demonstrate the existence of an evolutionary-developmental role for the pineal complex during growth, fertility, and aging. The dominant role of the pineal in the initiation and progression of aging as a death signal is clear, but its nature and mechanism are totally unknown. In fact new experiments showed that an additional pineal gland from a young donor, when grafted into a young mouse, induces acceleration of aging. The significance of these intriguing findings is discussed.

Age Factors↗
PubMed2001

Circadian programming in cyanobacteria.

Prokaryotic cyanobacteria express robust circadian (daily) rhythms under the control of a timing mechanism that is independent of the cell division cycle. This biological clock orchestrates global regulation of gene expression. Competition experiments demonstrate that fitness is enhanced when the circadian period is consonant with the period of the environmental cycle. Mutational analyses have identified three clock genes in the organism, one of which is related to DNA recombinases and helicases. We propose a new model for the core 'clockwork' that implicates rhythmic changes in the status of the chromosome that underly the rhythms of gene expression.

Biological Clocks↗
PubMed1999

Circadian programs in cyanobacteria: adaptiveness and mechanism.

At least one group of prokaryotes is known to have circadian regulation of cellular activities--the cyanobacteria. Their "biological clock" orchestrates cellular events to occur in an optimal temporal program, and it can keep track of circadian time even when the cells are dividing more rapidly than once per day. Growth competition experiments demonstrate that the fitness of cyanobacteria is enhanced when the circadian period matches the period of the environmental cycle. Three genes have been identified that specifically affect circadian phenotypes. These genes, kaiA, kaiB, and kaiC, are adjacent to each other on the chromosome, thus forming a clock gene cluster. The clock gene products appear to interact with each other and form an autoregulatory feedback loop.

Adaptation, Physiological↗
PubMed1996

Let there be light: signal transduction in a mammalian circadian system.

Mammalian circadian rhythms are controlled by a biological clock located in the hypothalamic suprachiasmatic nuclei (SCN). This clock is entrained by light through a retinohypothalamic pathway that interacts with the SCN through glutamate neurotransmission. Light pulses during the subjective night induce phase shifts of behavioral rhythms, and also trigger intracellular changes such as the expression of immediate-early genes and activation of transcription factors. In this review, we present a model of the signal transduction pathway leading to photic synchronization of the circadian clock, including the activity of specific second messenger systems, gene expression, and interaction between potential agents capable of producing phase shifts.

Animals↗
PubMed1976

The chronomutagenic effect of deuterium oxide on the period and entrainment of a biological rhythm. II. The reestablishment of lost entrainment by artificial LD cycles.

Mice caused to ingest 25% or 30% deuterium oxide could no longer be entrained to a 12:12 light-dark cycle. Reentrainment could be established by artificially lengthening the light-dark cycle from a natural 24-hours one, to LD 13:13 or 14:14. It is noted that the relationship between biological rhythms and the ambient LD cycle is strikingly similar to that between coupled unidirectional physical oscillators. It is concluded that while the similarity between the responses of a great many organismic rhythms to deuterium oxide administration suggests that the biological clocks of all organisms are very similar, if not the same, a substance with more specificity to key biological processes than D2O will be required to eventually elucidate the escapement mechanism of the enigmatic living clock.

Animals↗
PubMed2004

Circadian genes in a blind subterranean mammal III: molecular cloning and circadian regulation of cryptochrome genes in the blind subterranean mole rat, Spalax ehrenbergi superspecies.

The blind subterranean mole rat superspecies Spalax ehrenbergi is an extreme example of mammalian adaptation to life underground. Though this rodent is totally visually blind, harboring a drastically degenerated subcutaneous rudimentary eye, its daily activity rhythm is entrainable to LD cycles. This indicates that it confers light information to the clock, as has been previously shown by the authors in behavioral studies as well as by molecular analyses of its Clock/MOP3 and its three Per genes. The Cryptochrome (Cry) genes found in animals and plants act both as photoreceptors and as essential components of the negative feedback mechanism of the biological clock. To further understand the circadian system of this unique mammal, the authors cloned and characterized the open reading frame of Spalax Cry1 and Cry2. The Spalax CRY1 protein is significantly closer to the human homolog than to the mice one, in contrast to the evolutionary expectations. They have found two isoforms of Cry2 in Spalax, which differ in their 5' end of the open reading frame and defined their expression in Spalax populations. They found a large and significant excess of heterozygotes of sCry2 (sCry2L/S genotype). Both sCry1 and sCry2 mRNAs were found in the SCN, the eye, the harderian gland, as well as in a wide range of peripheral tissues. Their expression pattern under different LD conditions has also been analyzed. As was already shown for other circadian genes, despite being blind and living in darkness, the Cry genes of Spalax behave in a similar, though not identical, pattern as in sighted animals. Once again, the results indicate that the uniquely hypertrophied harderian gland of Spalax plays a key role in its circadian system.

Amino Acid Sequence↗