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 649 records · Page 36Linked to original sources
PubMed1991

Circadian myometrial and endocrine rhythms in the pregnant rhesus macaque: effects of constant light and timed melatonin infusion.

Six chronically catheterized rhesus macaques maintained on a 12-hour-light/dark cycle (lights on from 7 AM to 7 PM) showed a nocturnal uterine activity rhythm with peak contractile events between 9 and 11 PM (p less than 0.05). In blood samples collected at 3-hour intervals over a 24-hour period, we determined that plasma melatonin and progesterone concentrations were elevated at night whereas estradiol, estrone, and cortisol reached peak concentrations in the early morning (p less than 0.05). Lights were then left on for the remainder of the study. After 12 days in constant light, daily rhythms in uterine activity and plasma steroid levels were relatively unchanged, whereas melatonin concentrations were suppressed. Animals then received a timed infusion of melatonin (0.2 mg/kg/hr each day from 7 PM to 6 AM daily until delivery). The nocturnal uterine activity rhythm and the rhythms in plasma steroid concentrations were maintained. We conclude that the 24-hour patterns in maternal uterine activity and plasma steroid hormone levels are circadian rhythms generated by an endogenous biologic clock and do not appear to be driven by the pattern of melatonin in circulation.

Animals↗
PubMed1990

Aluminum fluoride reveals a phosphoinositide system within the suprachiasmatic region of rat hypothalamus.

The phosphoinositide (PI) transduction system has proven to be of major importance in several regions of mammalian brain. In this report, we examined in rats whether a PI system is present in the hypothalamic suprachiasmatic nuclei (SCN), the site of a biological clock that generate circadian rhythms. Autoradiographic localization of phorbol ester binding revealed moderate levels of protein kinase C, a component of the PI system, in the SCN. Hypothalamic explants containing SCN showed substantial incorporation of [3H]myoinositol into lipids. AlF4-, a non-specific activator of G proteins, produced a dose-dependent increase in inositol monophosphate (IP1) levels in the explants in calcium-free medium, with a maximum increase of 216% of control at 50 mM NaF. Medium containing 1.8 mM calcium stimulated a similar increase in IP1 levels, but the stimulatory effects of AlF4- and calcium were not additive, so that the effect of Al4- was obscured in medium containing calcium. AlF4- stimulated accumulation of IP1, as well as inositol bis-, and trisphosphate, over a 40-min time course in the presence and absence of lithium (10 mM LiCl). Lithium, a known inhibitor of phosphatases in the inositol phosphate recycling pathway, raised levels of all 3 inositol phosphates in SCN explants both at baseline (without A1F4-) and after 30 min AlF4- stimulation. The results show the existence of a lithium-sensitive PI system within the suprachiasmatic region of the rat hypothalamus.

Aluminum↗
PubMed1992

Development of inositol 1,4,5-trisphosphate 3-kinase immunoreactivity in cerebellar Purkinje cells in vivo and in vitro.

Development profiles in vivo and in vitro of inositol 1,4,5-trisphosphate 3-kinase (IP3K) were investigated immunohistochemically in the cerebellar Purkinje cells. In in vivo preparations of rat cerebellum, IP3K immunoreactivity appeared in Purkinje cell bodies and dendrites shortly after birth, increased rapidly by postnatal day 5, and was subsequently confined to their dendritic processes by day 20. The appearance and shift of IP3K immunoreactivity in Purkinje cells showed an identical time course even when Purkinje cells were placed under culture conditions commencing on day 0, suggesting that Purkinje cells have their own biological clock on the expression of IP3K in the absence of external influences.

Animals↗
PubMed1992

Circadian and developmental regulation of Oct-2 gene expression in the suprachiasmatic nuclei.

Oct-2 is a transcriptional activating factor that is expressed in the suprachiasmatic nuclei (SCN), the site of a biological clock. We examined in rats whether Oct-2 gene expression is regulated by the circadian pacemaker or by light using quantitative in situ hybridization. The ontogeny of Oct-2 gene expression in the SCN was also studied. Oct-2 mRNA levels remained constant throughout the circadian cycle. In contrast to c-fos mRNA levels which are acutely induced by acute light exposure at night, Oct-2 mRNA levels were not increased by light exposure at night. At gestational day 18, the first age the SCN are anatomically distinct, a prominent Oct-2 hybridization signal was present in the SCN. Our results suggest that Oct-2 is constitutively expressed in the SCN and is present from the time the SCN are discernible as discrete nuclei in fetal brain.

Animals↗
PubMed1992

Circadian rhythm of cell proliferation in the telencephalic ventricular zone: effect of in utero exposure to ethanol.

The neocortical ventricular zone is composed of a desynchronized population of proliferating cells. These cells give rise to neurons in the infragranular laminae of neocortex. The present study documents a diurnal rhythmicity of cell proliferation in the ventricular zone and examines the effects of ethanol on this biological clock. Pregnant rats were fed one of 3 diets. They were provided an ethanol-containing (6.7% v/v) liquid diet ad libitum between gestational day (G) 6 and G18, pair-fed an isocaloric liquid control diet, or fed chow and water. Throughout the experiments, the rats were fed either at 08.00 h (E.S.T) or at 17.00 h (lights on 06.00 to 18.00 h). Rats were given a single injection of bromodeoxyuridine (BrdU) on G17 at one point during a 24 h period (03.00, 06.00, 09.00 h, etc.). The fraction of ventricular cells that incorporated the BrdU was determined using quantitative immunohistochemical methods. Pair-fed control rats (fed at 08.00 or 17.00 h) consumed their food within 4 h of presentation. The ratio of cells passing through the S-phase of the cell cycle changed diurnally; the ratio was highest during the day (0.52 +/- 0.01 at 12.00 h) and lowest during the night (0.40 +/- 0.02 at 03.00 h). In contrast, the ethanol-fed rats grazed on their food throughout the dark cycle regardless of when the food was presented. The mean peak blood ethanol concentration was 142 +/- 13 mg/dl during the dark phase and less than 25 mg/dl during the light phase. Prenatal exposure to ethanol eliminates the fetal circadian rhythm in cell proliferation (mean labeling index of 0.45 +/- 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Serotonin receptor gene expression in the rat suprachiasmatic nuclei.

Serotonin (5HT) is thought to reset the biological clock in the suprachiasmatic nuclei (SCN) in vitro through a postsynaptic 5HT-1a receptor. Thus we examined 5HT receptor gene expression in the SCN by in situ hybridization. On film autoradiograms, 5HT-1c receptor mRNA showed intense SCN hybridization, while 5HT-1b receptor mRNA displayed a weaker signal. Emulsion autoradiograms additionally revealed expression of 5HT-1a and 5HT-2 receptor mRNAs by a few scattered SCN cells. 5HT-3 receptor mRNA was not detected in the SCN, although the transcript was detected elsewhere in the brain. 5HT-1d and -1e receptor mRNAs were not detected in the SCN or elsewhere in brain within the sections examined. The results do not support a major role for postsynaptic 5HT-1a receptors in resetting SCN rhythms.

Animals↗
PubMed1994

Expression of a multifunctional DNA repair enzyme gene, apurinic/apyrimidinic endonuclease (APE; Ref-1) in the suprachiasmatic, supraoptic and paraventricular nuclei.

Apurinic/apyrimidinic endonuclease (APE; also referred to as Ref-1) repairs oxidative damage to DNA and regulates the redox state of DNA binding proteins. This later property influences the ability of DNA binding proteins, which include Fos and Jun, to bind to AP-1 complexes. Since DNA binding proteins may play important roles in regulating neuronal activity in the hypothalamus, we examined the expression of APE in the hypothalami of rats. In situ hybridization studies revealed high levels of APE mRNA expression in the suprachiasmatic nuclei (SCN), supraoptic nuclei (SON) and paraventricular nuclei (PVN). Since the SCN are the site of a biological clock, we examined whether APE gene expression was regulated by the circadian cycle or by light. Quantitative in situ hybridization studies showed that APE mRNA levels remained constant over the circadian cycle and were not increased by light exposure at night. We also tested if APE expression was under osmotic control in the SON and PVN. Hypertonic stimulus, however, did not induce further expression of APE mRNA in either the SON or the PVN. These findings identify the SCN, SON and PVN as sites of high level APE gene expression. These data suggest that APE may play an important role in these structures either to facilitate DNA repair or DNA binding protein action.

Animals↗
PubMed1994

A period (per)-like protein exhibits daily rhythmicity in the suprachiasmatic nuclei of the rat.

The period (per) gene of Drosophila melanogaster is considered an important biological clock gene, since it regulates multiple behavioral rhythms. Per mRNA and protein exhibit circadian rhythms in the fruitfly brain and these rhythms appear to influence each other through a feedback loop. More recently, using the same antibody as was used in the Drosophila studies, PER-like proteins were detected in the suprachiasmatic nuclei (SCN) of male rats. This region of the brain is considered to be a major neural circadian pacemaker in mammals. The purpose of this study was to confirm that PER-like proteins are detectable in the SCN of female rats and to determine whether PER-like proteins exhibit a circadian rhythm. Female rats were killed at several times of day under both light/dark and constant conditions. Using the same anti-PER antibody in Western blots with Enhanced Chemiluminescence (Western-ECL) detection, the levels of the PER-like proteins were quantified in the SCN and cerebral cortex. The antibody identified a doublet band of approximately 170-160 kDa and a single band at 115 kDa. Of the three PER-like proteins only the largest exhibited a daily rhythm in the SCN, which peaked in the middle of the dark and attained its nadir around lights off; levels during the light were intermediate with a tendency towards a second drop around lights on. This rhythm did not persist under constant dim red light.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Mutagenesis and behavioral screening for altered circadian activity identifies the mouse mutant, Wheels.

The molecular processes underlying the generation of circadian behavior in mammals are virtually unknown. To identify genes that regulate or alter circadian activity rhythms, a mouse mutagenesis program was initiated in conjunction with behavioral screening for alterations in circadian period (tau), a fundamental property of the biological clock. Male mice of the inbred BALB/c strain, treated with the potent mutagen N-ethyl-N-nitrosourea were mated with wild-type hybrids. Wheel-running activity of approximately 300 male progeny was monitored for 6-10 weeks under constant dark (DD) conditions. The tau DD of a single mouse (#187) was longer than the population mean by more than three standard deviations (24.20 vs. 23.32 +/- 0.02 h; mean +/- S.E.M.; n = 277). In addition, mouse #187 exhibited other abnormal phenotypes, including hyperactive bi-directional circling/spinning activity and an abnormal response to light. Heterozygous progeny of the founder mouse, generated from outcrossings with wild-type C57BL/6J mice, displayed lengthened tau DD although approximately 20% of the animals showed no wheel-running activity despite being quite active. Under light:dark conditions, all animals displaying circling behavior that ran in the activity wheels exhibited robust wheel-running activity at lights-ON and these animals also showed enhanced wheel-running activity in constant light conditions. The genetic dissection of the complex behavior associated with this mutation was facilitated by the previously described genetic mapping of the mutant locus causing circling behavior, designated Wheels (Whl), to the subcentromeric portion of mouse chromosome 4. In this report, the same locus is shown to be responsible for the abnormal responses to light and presumably for the altered circadian behavior. Characterization of the gene altered in the novel Whl mutation will contribute to understanding the molecular elements involved in mammalian circadian regulation.

Animals↗
PubMed1983

A stone's throw and its launch window: timing precision and its implications for language and hominid brains.

Did bigger brains for more precise throwing lead to language, much as feathers for insulation may have set the stage for bird flight? Throwing rocks even at stationary prey requires great precision in the timing of rock release from an overarm throw, with the "launch window" narrowing eight-fold when the throwing distance is doubled from a beginner's throw. Paralleled timing neurons can overcome the usual neural noise limitations via the law of large numbers, suggesting that enhanced throwing skill could have produced a strong selection pressure for any evolutionary trends that provided additional timing neurons. This enhanced timing circuitry may have developed secondary uses for language reception and production.

Animals↗
PubMed1984

Self-transcription: RNA polymerase transcription of its own genes, and its role in cellular differentiation and cell cycling.

The concept of RNA polymerase self-transcription, where eukaryotic RNA polymerase II and prokaryotic holoenzyme are responsible for transcription of their own genes, would give these enzymes a unique role in the cellular transcriptional and translational machinery. This self-transcriptional ability would equip a cell with an exquisite mechanism of autogenous regulation for the appearance of these transcriptional units. Such a mechanism could allow layering of other transcriptional control pathways upon the RNA polymerase self-transcriptional pathway, thus forming a complex array of mechanisms to regulate transcription of genes concerned with cellular differentiation and cell cycling. It is proposed that RNA polymerase self-transcription is the central control point of gene expression in cellular differentiation and for cell cycling, thus fulfilling the role of an intrinsic biological clock.

Animals↗
PubMed1994

Function of melatonin in thermoregulatory processes.

Accumulated information shows that, besides its role in the timing of seasonal reproduction, melatonin also plays an important role in seasonal thermoregulatory adjustments of animals including torpor and hibernation. Furthermore, melatonin has a crucial role in circadian thermoregulatory adjustments of body temperature (Tb). Melatonin appears to send signals to the preoptic area of anterior hypothalamus (PoAH) where it adjusts the set point of Tb consistent with the metabolic rate of the animal. This new function for melatonin as a transducer mediating information about energy balance has been suggested in this review. Melatonin also adjusts the activity of the biological clock in vertebrates.

Animals↗
PubMed1983

Heat balance of rats acclimated to diurnal 2-hour feeding.

Heat production (M) and heat loss (H) of ad lib fed rats and of rats fed for 2-hr daily for 2 months (2-hr fed rats) were simultaneously measured by direct and indirect calorimetry over a period of 48 hours. The ad lib fed rats showed a clear nocturnal increase in M and H, which consisted of several discrete increases associated with discrete rises in feeding activity. In each increase, however, M and H were somewhat out of phase with each other. During feeding, a positive shift of heat storage occurred, which was repaid by H being higher than M thereafter. No such increases of M and H were observed in either the fasted ad lib fed rats or the 2-hr fed rats. The 2-hr fed rats showed a very large increase in M and H following the meal, which obscured the nocturnal increase of metabolic rate. Without food, this diurnal increase was greatly reduced but not to the minimum level, and two definite peaks of M and H associated with increased food exploratory activity, one in the day and the other at night, were obtained. There was a sharp fall in RQ 1-2 hr prior to the diurnal feeding. These observations suggest that, besides diet-induced heat production, feeding can be an additional time cue for increasing energy metabolism, but a more basic biological clock mechanism synchronizing the day-night cycle drives circadian rhythms of physical activity and biochemical processes related to energy expenditure in rats.

Animals↗
PubMed1991

Influence of running wheel activity on free-running sleep/wake and drinking circadian rhythms in mice.

Previous studies have indicated that manipulation of activity levels can modify characteristics of sleep/wake and activity rhythms. The generality of these observations was evaluated by simultaneously measuring drinking and sleep/wake rhythms while mice had free or no access to a running wheel in constant conditions (DD). Robust circadian rhythms in all parameters were observed in the "wheel free" (unrestricted) condition. When wheels were locked, the peak amplitude of the sleep/wake circadian rhythm decreased by approximately 50% without affecting the amplitude of the drinking rhythm. Total wake time decreased 11% per circadian day when wheels were locked with increases in both NREM and REM sleep. Whereas the amplitude of the drinking waveform was unaffected, wheel restriction caused an equivalent increase in period length (tau) for both rhythms. These results indicate that, unlike the generalized effects of activity on tau, activity restriction influences on rhythm amplitude do not generalize to all behavioral and/or physiological variables. This work also supports the notion that activity influences on sleep/wake rhythm amplitude reflect behavioral "masking" rather than a fundamental change in the direct coupling mechanisms of the biological clock.

Animals↗
PubMedDate not supplied

Adapting to phase shifts, II. Effects of melatonin and conflicting light treatment.

The effects of melatonin (MT) and placebo (P) on adaptation to a rapid 9-h advance phase shift, in the presence and absence of inappropriate bright light (BL) exposure were examined. Volunteers were initially subjected to a gradual 9-h delay phase shift over 5 days (D1-D5) using a combination of bright light and darkness/sleep. Readaptation to a subsequent rapid 9-h advance phase shift was studied using: 1) MT, 5 mg, 2300 h, D6-D8, 2) BL, 2,000 lx, 0800-1200 h, D7-D8, 3) MT+BL and 4) P, 2300 h, D6-D8. MT treatment was timed to phase advance and BL to phase delay. BL delayed the 6-sulphatoxymelatonin rhythm in five out of seven subjects. Two subjects delayed and five phase advanced with both MT and MT+BL. MT consistently improved subjective sleep, alertness, and performance even in the presence of inappropriate BL and before phase readaptation had occurred. BL improved alertness and performance transiently. The beneficial effects of MT are not wholly mediated through an effect on the biological clock.

Adaptation, Psychological↗
PubMed1989

Fate of allogeneic embryonal chick chondrocytes implanted orthotopically, as determined by the host's age.

Chondrocytes derived from chick embryos can be successfully implanted in defects of adult chick articular cartilage surfaces. Such implants thrive in their implantation site and create a new articular surface. The chondrocytes mature and hypertrophy in the orthotopic site without invoking an immune response. Eventually a steady state is reached in which mature chondrocytes resurface the defect while in the deeper areas spongy bone replaces the hypertrophic chondrocytes. Time schedules of these repair events have been studied in hosts of different ages. We compared 4-month-old chicks with 3-year-old chickens. The embryonal chondrocytes implanted in the latter group underwent an accelerated aging process. The defects were completely filled-up after 1 month as compared with 2-3 months in the younger age group. Endochondral ossification in the older group was evident as early as 2 months post implantation and was completed after 6 months. This contrasts with the situation in the younger group where the chondrocytes only began to hypertrophy after 6 months. At this stage endochondral ossification was hardly seen at all. A unique response to the cartilaginous implants is seen in the old group only in the vicinity of the reparative tissue, accumulation of hematopoietic centers. This study seem to indicate that the host's environment affects the "biological clock", i.e. rate and degree of aging of the implanted cells, as well as their matrices.

Age Factors↗