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Results for “Biological Clocks”

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PubMed1979

Kinetics of the cycloheximide-induced phase changes in the biological clock in Gonyaulax.

Cycloheximide, an inhibitor of protein synthesis on cytoplasmic ribosomes in eukaryotes, is shown to shift the phase of the circadian rhythm in stimulated bioluminescence in the marine dinoflagellate Gonyaulax polyedra. Kinetic analysis of the phase changes shows that this effect may be subdivided into two distinctly different and well-separated parts. The first (early) phase change occurs with 15-min exposure to cycloheximide and is saturated at low concentrations ( approximately 10 nM). The second (late) phase changes requires about 150 min of exposure to cycloheximide and is saturated at 0.36 muM cycloheximide. Twenty-times-higher concentrations cause no further phase changes. The magnitudes of both early and late phase changes depend on the time of day when the cells are exposed to cycloheximide. Early phase changes vary from 5 hr advance at circadian time (CT) 20 to 1 hr delay at CT 12; late phase changes are larger, the maximal advance being 12 hr at CT 16 and the greatest delay, 10 hr at CT 14. It is proposed that the early phase changes are caused by alterations in the ion distribution across membranes as a consequence of the permeation of cycloheximide. Late phase changes may be the result of inhibition of protein synthesis.The phase response curve for the late phase change is identical to that obtained with saturating light pulses in otherwise constant darkness in Gonyaulax. Maximal phase changes drive the clock into the part of the circadian cycle between CTs 4 and 9. Perturbations in this part of the circadian cycle are without effect on phase. Incubation of Gonyaulax with cycloheximide for a critical duration at a critical time induces arhythmicity, but longer exposures to the inhibitor at the same time do not. This observation suggests the existence of a singularity in the circadian clock of Gonyaulax.

Journal Article↗
PubMed1984

Molecular genetics of a biological clock in Drosophila.

Ninety kilobase pairs (kb) of DNA have been isolated from the 3B region of the X chromosome of Drosophila melanogaster. Previous cytogenetic analyses have placed a gene required for rhythmic behavior (per) in this chromosomal interval. Physical characterization of a series of chromosomal rearrangements altering per locus activity indicates that DNA affecting behavioral rhythms is found in a 7.1-kb HindIII fragment. A single 4.5-kb poly(A)(+) RNA is transcribed from this DNA in wild-type pupae and adult flies. The transcript is eliminated by a per mutant that retains some rhythmic activity, but this mutant substitutes two novel transcripts, 11.5 kb and 0.9 kb. It is suggested that the new poly(A)(+) transcripts provide residual per locus activity.

Journal Article↗
PubMed2000

Decreased vasopressin gene expression in the biological clock of Alzheimer disease patients with and without depression.

Circadian rhythm disturbances are frequently present in Alzheimer disease (AD). In the present study, we investigated the expression of vasopressin (AVP) mRNA in the human suprachiasmatic nucleus (SCN). The in situ hybridization procedure on formalin-fixed paraffin-embedded material was improved to such a degree that we could, for the first time, visualize AVP mRNA expressing neurons in the human SCN and carry out quantitative measurements. The total amount of AVP mRNA expressed as masked silver grains in the SCN was 3 times lower in AD patients (n = 14; 2,135 +/- 597 microm2) than in age- and time-of-death-matched controls (n = 11; 6,667 +/- 1466 microm2) (p = 0.003). No significant difference was found in the amount of AVP mRNA between AD patients with depression (n = 7) and without depression (n = 7) (2,985 +/-1103 microm2 and 1,285 +/- 298 microm2, respectively; p = 0.38). In addition, the human SCN AVP mRNA expressing neurons showed a marked day-night difference in controls under 80 years of age. The amount of AVP mRNA was more than 3 times higher during the daytime (9,028 +/- 1709 microm2, n = 7) than at night (2,536 +/- 740 microm2, n = 4; p = 0.02), whereas no clear diurnal rhythm of AVP mRNA in the SCN was observed in AD patients. There was no relationship between the amount of AVP mRNA in the SCN and age at onset of dementia, duration of AD and the neuropathological changes in the cerebral cortex. These findings suggest that the neurobiological basis of the circadian rhythm disturbances that are responsible for behavioral rhythm disorders is located in the SCN. It also explains the beneficial effects of light therapy on nightly restlessness in AD patients.

Aged↗
PubMed1968

Pineal function: the biological clock in the sparrow?

The pineal organ of the house sparrow, Passer domesticus, is essential for persistence of the circadian locomotor rhythm in constant conditions. Upon removal of the pineal body, activity becomes arrhythmic. However, pinealectomy does not abolish the rhythm of locomotor activity in birds exposed to light-dark cycles. Pinealectomized birds are entrained by light cycles in much the same manner as are normal birds. Our data demonstrate that the pineal organ is a crucial component of the endogenous time-measuring system of the sparrow.

Animals↗
PubMed1983

Maternal coordination of the fetal biological clock in utero.

Deoxyglucose labeled with carbon-14 was used in studying the utilization of glucose in the suprachiasmatic nuclei of fetal rats. The results showed that an entrainable circadian clock is present in the suprachiasmatic nuclei during fetal development and that the maternal circadian system coordinates the phase of the fetal clock to environmental lighting conditions.

Animals↗
PubMed1994

[A biological clock in the brain--the suprachiasmatic nucleus of the hypothalamus].

Rhythms of 24 hr periodicity underlie most aspects of daily life, although we are rarely aware of its presence. This circadian rhythmicity is a consequence of evolution of the living organism, which takes place on the earth for millions of years. Some of these rhythms are actually derived from an endogenous oscillating mechanism whose inherent period is not exactly 24 hrs. Therefore, it must be constantly adjusted to the solar cycle of day and night. It has been firmly established that the suprachiasmatic nucleus (SCN) of the hypothalamus is the highest center of these endogenous circadian rhythms. Lesions of the SCN eliminates most behavioral and physiological rhythms and actvities of the SCN exhibited a dramatic change between day and night. Furthermore, rhythms of SCN neurons persist under in vitro conditions. The cellular or molecular mechanism for these neurons to generate a 24 hr rhythm is unclear at present. The SCN contains many neuropeptides and some of them display circadian rhythms, while others do not. We found that this distinct behavior of peptides in the SCN was due to different regulation of MRNA or gene transcription. This observation indicate the possibility that genes are involved in the generation of circadian rhythms in the SCN.

Animals↗
PubMed1981

Catecholamine neurotransmitters, psychoactive drugs, and biological clocks. The 1981 Harvey Cushing oration.

In his Cushing oration, the 1970 Nobel Laureate reviews the experimental history of the vital role which chemical agents play in the transmission of nerve impulses and the important functions of the brain. He reveals the intriguing steps in his own early involvement in the field of neurotransmitters. A beacon for neuroscientists of the future is his unique talent for not only looking, but seeing potentially significant clues.

Animals↗
PubMed2000

Collagen fragments in urine derived from bone resorption are highly racemized and isomerized: a biological clock of protein aging with clinical potential.

Fragments of the alpha1 C-terminal telopeptide of type I collagen containing the sequence AHDGGR(1209-1214) (CTx) can be measured in urine as an index of bone resorption. We report here that these molecules undergo racemization and isomerization of Asp(1211) in vitro and in vivo, generating a mixture of four isomers: the native peptide form (alphaL), an isomerized form containing a beta-Asp bond (betaL), a racemized form containing a D-Asp residue (alphaD) and an isomerized/racemized form (betaD). To study these reactions at this specific site in collagen, we have employed four immunoassays, each specific for one of the isoforms, and developed HPLC methods for their separation. The kinetics of these reactions were studied in vitro under physiological conditions by incubation of synthetic AHDGGR hexapeptide or mineralized bone collagen. Reactions were found to be strongly shifted towards the beta-Asp forms and slightly in favour of the D-enantiomeric forms. CTx isomers were measured in human urine and in enzymic digests of bovine bone collagen. The results indicated that the extent of racemization and isomerization were correlated with the age and turnover of collagen. The ratios between the native and age-related forms of CTx were elevated in urine from patients with Paget's disease or osteoporosis as compared with that from healthy adults. The alphaL/alphaD CTx ratio had the highest discriminatory power (T-score=23.2; P<0.0001 and T-score=1. 5; P<0.0001 for Paget's disease and osteoporosis respectively). In conclusion, these findings indicate that an assessment of CTx ratios in urine may provide an estimate of bone turnover, aiding in the diagnosis of metabolic bone diseases.

Adult↗
PubMed2000

The human body circadian: How the biologic clock influences sleep and emotion.

Diurnal, nocturnal or seasonal modes of behavior are not passive responses to changes in the environment; rather, they are generated by an endogenous circadian pacemaker, entrained by a few environmental cues like lightdark cycles. Circadian clock mechanisms involve periodic gene expression, synchronized by a hierarchically superior structure located in mammals in the hypothalamic suprachiasmatic nuclei. Cycles of sleep and wakefulness are the most conspicuous circadian rhythm. Since modern humans use artificial light to extend their period of wakefulness and activity into the evening hours, they adhere to a shortnight sleep schedule with a highly consolidated and efficient sleep. As shown by studies in artificial long nights, modern humans may be sleepdeprived. Humans have also increasingly insulated themselves from the natural cycles of light and darkness. Still, the human circadian pacemaker has conserved a capacity to detect seasonal changes in day length. A mood disorder involving a recurring autumn or winter depression (seasonal affective disorder, SAD) is related to latitude, with the number of cases increasing with distance from the equator. SAD is ameliorated by using brilliant light. In nonseasonal depression, mood typically fluctuates daily, with improvement over the course of the day, and various physiological functions exhibit an altered circadian pattern, suggesting a link with circadian disruption. Treatment of circadian rhythm disorders, whether precipitated by intrinsic factors (e.g., sleep disorders, blindness, mental disorders, aging) or by extrinsic factors (e.g., jet lag, shift work) has led to the development of a new type of agents called "chronobiotics," among which melatonin is the prototype.

Journal Article↗