Control Of Circadian Rhythms Research Articles

Differential effect of restraint stress on MHC class II expression by murine peritoneal macrophages

The effect of restraint stress on the expression of MHC class II glycoproteins by peritoneal macrophages was evaluated. Restraint suppressed the expression of I-A by macrophages from mice that are susceptible to Mycobacterial infection. In contrast, restraint did not affect I-A expression by macrophages from resistant mice. The suppression of MHC class II expression required at least 8 h of restraint and recovered within 4 h after stress. The amount of restraint necessary to suppress I-A expression also resulted in higher levels of plasma corticosterone. Changes in I-A expression were under circadian rhythm control. The differences in the effect of restraint stress on expression of I-A by peritoneal macrophages from resistant and susceptible mice may, in part, be due to differences in the effect of corticosterone in MHC class II expression.

The role of the pineal gland in the control of circadian locomotor activity rhythms in the lacertid lizardPodarcis sicula campestris

The role of the pineal gland in the control of circadian locomotor activity rhythms in the lacertid lizard<i>Podarcis sicula campestris</i>

Olfactory bulb control of circadian activity rhythm in mice

Ablation of mouse olfactory bulbs lengthened the circadian period of wheel-running activity by 43 min and delayed the onset of entrained activity by 108 min. A transient increase in activity during the light phase of the 12:12 h light-dark photoperiod also occurred following surgery. These disruptions suggest that olfactory systems can modulate mammalian circadian rhythms.

Circadian rhythms in spontaneous neuronal discharges of the cultured suprachiasmatic nucleus

The suprachiasmatic nucleus (SCN) is believed to play a major role in the generation and control of circadian rhythms in mammals. In order to obtain further evidence concerning this, single and multiple neuronal discharges were continuously recorded over a period of several days in neonatal rat SCN explants. These organotypic explants, which had been cultured for several werks in a chemically defined medium, showed alternating high and low levels of spontaneous neuronal discharges with a periodicity around 24 h. Such explants can serve as a useful model to study the neuronal mechanisms underlying the generation of mammalian circadian rhythms.

24-Hour Profiles of Blood Pressure and Heart Rate in Cushing's Syndrome: Relationship Between Cortisol and Cardiovascular Rhythmicities

We monitored the circadian profiles of cortisol, systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR) in 33 matched normotensive subjects, 32 patients with essential hypertension and 16 patients with Cushing's Syndrome (8 pituitary adenomas, 6 adrenal adenomas and 2 adrenal carcinomas). Each subject underwent serial blood drawings at 4-hr intervals along the 24-hr cycle. BP and HR were automatically recorded every 30 min. Data were analyzed by conventional statistics and by chronobiological procedures (cosinor rhythmometry). Both the control subjects and essential hypertensives showed a circadian profile of BP and HR characterized by a peak in the early afternoon and a clear nocturnal fall (rhythm detection: P less than 0.001). The rhythmicity of BP was disrupted in patients affected by Cushing's Syndrome, whereas the 24-hr oscillation of HR was preserved (P less than 0.001). Our data are compatible with the view that glucocorticoids are involved in the control of BP circadian rhythm, whereas HR is not under their control.

Pineal and retinal melatonin is involved in the control of circadian locomotor activity and body temperature rhythms in the pigeon

Although pinealectomy or blinding resulted in loss of the clarity of the free-running rhythm of locomotor activity and body temperature and reduced the peak level of circulating melatonin rhythms to approximately a half in intact pigeons, neither pinealectomy nor blinding abolished any of these rhythms. However, when pinealectomy and blinding were combined, the rhythms of locomotor activity and body temperature disappeared in prolonged constant dim light, and melatonin concentration was reduced to the minimum level of detection. In order to examine the role of melatonin in the pigeon's circadian system, it was administered either daily or continuously to PX + EX-pigeons in LLdim. Daily administration of melatonin restored circadian rhythms of locomotor activity which entrained to melatonin injections, but continuous administration did not induce any remarkable change of locomotor activity. These results suggest that melatonin synthesized in the pineal body and the eye contributes to circulating melatonin and its rhythmicity is important for the control of circadian rhythms of locomotor activity and body temperature in the pigeon.

Circadian rhythm and phytochrome control of LHC-I gene transcription

A small amount of translatable mRNA for a nuclear-coded precursor apoprotein of the LHC-I (light-harvesting complex of photosystem I) with a molecular mass of 26 kDa is present in etiolated bean leaves. The expression of this protein is phytochrome-controlled and follows circadian oscillations, for the appearance of which a red-light pulse is sufficient. The rhythmical oscillations persist for many hours in the dark following the red-light pulse or in continuous white light. The similarity of this rhythm in the light-induced accumulation of LHC-I mRNA with that of LHC-II mRNA [(1989) Plant Physiol. 90, 665] suggests that the same oscillator may govern the expression of all chloroplast protein genes regulated by light.

Involvement of the hypothalamo—pituitary—adrenal axis in the control of circadian blood pressure rhythm

The circadian blood pressure rhythm was compared between patients with Cushing's syndrome and those with essential hypertension or primary aldosteronism. In patients with essential hypertension or primary aldosteronism, clear nocturnal falls in systolic and diastolic blood pressure and the heart rate were observed. In contrast, in patients with Cushing's syndrome there was no nocturnal fall in blood pressure, and even a rise in some cases. In all cases with Cushing's syndrome, there was a nocturnal fall in the heart rate. Exogenous glucocorticoid abolished a nocturnal fall of blood pressure in patients with chronic glomerulonephritis or systemic lupus erythematosus, but did not affect nocturnal falls in the heart rate. These results indicate that the normal circadian rhythm of blood pressure may be regulated, at least in part, by the hypothalamopituitary-adrenal system.

Melatonin and the circadian rhythms of feeding and perch-hopping in the European starling,Sturnus vulgaris

The role of melatonin plasma titers in the control of free-running circadian rhythms was investigated in European starlings,Sturnus vulgaris, held in continuous dim light. Simultaneous recordings of plasma melatonin, perch-hopping and feeding activity revealed synchronous circadian variations in all three functions with high melatonin titers during resting and low titers during activity periods. Implanting birds with melatonin silastic capsules resulted in a 100-fold increase in plasma concentrations and an abolition of the endogenous melatonin rhythm. Feeding rhythms persisted during this treatment, although the activity time (α) was lengthened and the circadian period (τ) shortened. Similar changes were found in perchhopping activity, but in some birds, this activity was more or less suppressed. These data demonstrate that although melatonin plasma titers freerun synchronously with other circadian parameters, fluctuations in peripheral melatonin are not essential for the expression of circadian activity.

An ergonomic approach to stress.

The relationships between psychology and ergonomics centre around the concept of stress. This paper outlines the concept that stress is a mismatch between the demands made on an individual and his ability to cope. The nature and theories of stress are reviewed and sources of stress in the nursing profession are analysed. Coping is recognized as a way of reducing the actual or perceived stresses. However, a common method of coping is to disguise the symptoms by taking therapeutic drugs, tobacco or alcohol. It is argued that these methods are a maladaptation since in themselves they can cause illness and death. Evidence of smoking habits in relation to perceived stress in the nursing profession is given. It is concluded that a direct action approach to reduce workplace (organizational) stressors can be achieved by an ergonomic approach to the problem, and that this, if successful, will obviate the need to resort to unhealthy coping mechanisms. Suggestions are put forward as to how some of the major recognised sources of stress in the nursing profession can be analysed and removed by applying ergonomic methods. Shift working is seen by many nurses as a particular stressor. The relationships between lighting quality and circadian rhythm control are discussed as a further example of how an ergonomic solution might be sought.

Pharmacological Manipulation of the Serotoninergic Input to the Suprachiasmatic Nucleus—An Insight into the Control of Circadian Rhythmsa

Pharmacological Manipulation of the Serotoninergic Input to the Suprachiasmatic Nucleus—An Insight into the Control of Circadian Rhythms^a

The neuropharmacological approach to the study of the central control of circadian rhythmicity in animal behaviour

The neuropharmacological approach to the study of the central control of circadian rhythmicity in animal behaviour

Propylthiouracil causes phase delays and circadian period lengthening in male and female hamsters.

The thyroid neuroendocrine axis has been implicated in the control of circadian rhythmicity. The present work examined the ability of a thyroid hormone-inhibiting agent, propylthiouracil (PTU), to modulate phase and period of the hamster wheel-running circadian rhythm. The circadian period (tau) of blind male hamsters was lengthened by approximately 0.2 h when they were fed a diet containing 0.6% PTU. Removal of the PTU reversed the change in tau. Pinealectomy did not alter the tau response to PTU. Blind ovariectomized female hamsters showed changes in tau during and after PTU treatment that were similar to those of males. Males were also tested with 0.3, 0.6, or 1.2% PTU diets, and a dose-response relationship was established. Under 14:10 light-dark (LD 14:10) conditions, the phase of activity onset relative to lights off (psi) was not affected by 0.6% PTU. In LD 6:18, mean psi was 16.7 h, but this shortened to 13.3 h during PTU, returning to 16.0 h after PTU removal. In intact males under LD 14:10, the three PTU diet concentrations failed to differentially suppress thyroxine and triiodothyronine levels. Food intake and body weight were differentially reduced by the PTU treatments. A 0.5% quinine hydrochloride diet also reduced food intake and body weight but did not change tau. The inconsistency between the dose-tau response and the dose-thyroid hormone response suggest that PTU may affect circadian rhythmicity independent of its action on the thyroid neuroendocrine axis.

Neurochemical basis for the photic control of circadian rhythms and seasonal reproductive cycles: role for acetylcholine.

A pharmacological approach was used to examine the role of acetylcholine in the photic control of circadian rhythms and seasonal reproductive cycles. The experimental protocol was designed to determine whether the administration of carbachol, a cholinergic agonist, could mimic the effects of brief light pulses on gonadal function and/or the circadian rhythm of wheel-running activity in golden hamsters. Intraventricular injections of carbachol, administered singularly at discrete phase points throughout the circadian cycle, induced phase-dependent shifts in the free-running rhythm of activity similar to those caused by a brief light exposure. Injections of carbachol once every 23.33 hr for 9 weeks entrained the activity rhythm and stimulated the neuroendocrine-gonadal axis in a manner similar to that observed after the presentation of 1-hr light pulses at this frequency. In contrast, the administration of carbachol once every 24 hr did not consistently provide an entraining signal for the activity rhythm and did not stimulate reproductive function. Importantly, the effects of carbachol on the seasonal reproductive response were correlated with the timing of the injections relative to the activity rhythm. These findings suggest that acetylcholine may play an important role in the mechanism by which light regulates circadian rhythms and seasonal reproductive cycles.

Daily rhythms of benzodiazepine receptor numbers in frontal lobe and cerebellum of the rat

Behavioural, biochemical and neurophysiological evidence suggests that gamma-aminobutyric acid (GABA) may play an important role in the neural control of circadian rhythms. Central receptors for benzodiazepines are functionally coupled to GABA receptors and appear to mediate behavioural effects of exogenous benzodiazepines. The binding of 3H-flunitrazepam to synaptic plasma membranes prepared from various regions of rat brain was examined at 6-hour intervals over a 36-hour period. Prominent daily rhythms in receptor number (Bmax) were observed in the frontal lobe and the cerebellum but not in the temporoparietal regions, hypothalamus or medulla/pons. Binding was highest during periods of sleep/low activity with a significant decrease occurring just prior to waking. These results suggest that daily fluctuations in benzodiazepine receptor numbers may be related to the temporal control of sleep/wake and muscle activity cycles.

Differences in the ability of reserpine and chlorpromazine to block ovulation throughout the estrous cycle of the rat

Abstract Rats with a 4‐day estrous cycle were given a single dose of reserpine (62.5, 125, 500, 1000 or 2000 μg/kg body wt) or chlorpromazine (1, 2.5 or 5 mg/kg body wt) at 13.00 h on the days of estrus, diestrus 1, diestrus 2 or proestrus and were autopsied on the next expected day of estrus. The doses of reserpine (in μg/kg body wt) necessary to block ovulation during the cycle were 500 at estrus, 62.5 at diestrus 1, 500 at diestrus 2 and 2000 at proestrus, and for chlorpromazine (in μg/kg body wt) 2.5 on diestrus 1 and diestrus 2 and 1 in proestrus. On estrus, at 13.00 h, chlorpromazine was ineffective to block ovulation. A single dose of reserpine (125 μg/kg) or chlorpromazine (2.5 mg/kg) was given at estrus, diestrus 1 or diestrus 2 at 09.00, 13.00, 17.00 or 21.00 h, autopsy again being performed on the next expected day of estrus. The ability of reserpine to block ovulation begins at 17.00 on estrus, reaches its maximum throughout diestrus 1 and disappears at diestrus 2. Chlorpromazine ability to block ovulation appeared to have a circadian rhythm on diestrus 1 and diestrus 2, with a maximum at 13.00 and a minimum at 21.00 h, and no effect on estrus. Hormone replacement (human chorionic gonadotrophin) on diestrus 1, diestrus 2 and proestrus re‐established ovulation in rats whose ovulation was blocked by reserpine on diestrus 1 (125 μg/kg) and had no effect when the replacement was done only on diestrus 1 or diestrus 2. Rats blocked with chlorpromazine (1 mg/kg) on proestrus ovulated 24 hrs after the next expected day of estrus. The weight of the ovaries diminished in almost all rats treated with chlorpromazine, while the effects of reserpine depend on the dose used and the day of the cycle considered. Results obtained in these experiments suggest that the dopaminergic system susceptible to blocking by chlorpromazine, stimulates gonadotrophin control secretion on diestrus 1, diestrus 2 and proestrus. On diestrus 1 and diestrus 2, a circadian rhythm control system linked to dopaminergic system might exist. Blockade induced by reserpine might be related to changes observed in the hypothalamus content of norepinephrine throughout the estrus cycle, and also to the blockade on ovarian innervation exerted by reserpine.

Effects of partial destruction of the suprachiasmatic nuclei on two circadian parameters: wheel-running activity and short-day induced testicular regression

Many circadian rhythms in mammals are regulated by the suprachiasmatic nuclei located in the anterior hypothalamus. The suprachiasmatic nuclei are a heterogeneous population of neurons loosely segregated into regions. In an effort to determine if a regional specificity of control of different circadian rhythms exists within the SCN, the effect of small electrolytic lesions of the suprachiasmatic nuclei was examined on two parameters which are known to depend on the circadian system for their normal expression: wheel-running activity and short-day induced testicular regression. While some SCN lesions altered both the circadian rhythm of locomotor activity and the normal temporal pattern of gonadal regression on short-days, other partial lesions of the suprachiasmatic nuclei were found to effect one parameter without effecting the other. Detailed histological analysis of the neural damage sustained by the suprachiasmatic nuclei did not indicate an obvious regional specificity of function within the nuclei. However, the results do suggest that functionally specific neural pathways emerging from the suprachiasmatic nuclei carry circadian information to independent neural circuits responsible for locomotor activity and neuroendocrine-gonadal function.

Efferent control of circadian rhythms in the Limulus lateral eye.

Efferent control of circadian rhythms in the Limulus lateral eye.

Circadian variation in plasma corticosterone in the American alligator, Alligator mississippiensis, and the effects of ACTH injections

Crocodilians are unique among the reptiles in that they lack a pineal gland. Since the pineal is believed to play a role in the regulation of photoperiodic control of circadian rhythms in activity and corticosterone secretion in vertebrates, plasma corticosterone was measured by radioimmunoassay (RIA) in samples collected over a 24-hr period from captive-reared, juvenile crocodilians ( Alligator mississippiensis) held under a constant temperature but exposed to natural photoperiod. A clear biphasic rhythm in plasma corticosterone levels was observed, with a peak at 0800 hr and a second peak at 2000 hr, which corresponds to the biphasic activity cycle of this reptile. A single injection of 8 IU of mammalian ACTH into juvenile alligators resulted in a significant increase in corticosterone levels by 1 hr; hormone levels remained elevated for 24 hr, returning to baseline by 48 hr. Whereas handling and bleeding the alligators caused a significant increase in plasma corticosterone at 1, 4, and 24 hr, hormone levels in the ACTH-injected animals were significantly higher than the saline-injected controls at these times. Corticosterone levels in alligators range between 0.1 and 6 ng/ml as measured by RIA. These values are an order of magnitude lower than values previously reported for crocodilians.

Unilateral lesions of the hamster suprachiasmatic nuclei: evidence for redundant control of circadian rhythms

Several properties of vertebrate circadian rhythms can be attributed to the behavior of an underlying pacemaker system which is composed of two separate but mutually interacting circadian oscillators. As originally formulated, the model for such a pacemaker system proposed that two oscillators or populations of oscillators have different properties, specifically in their responses to light (Pittendrigh 1974; Pittendrigh and Daan 1976b). We have tested the proposition that the right and left suprachiasmatic nuclei (SCN) of the golden hamster contribute in different ways to the regulation of circadian rhythmicity by measuring the wheel-running activity rhythms of hamsters with lesions to either the right or left SCN. Although effects of unilateral or other partial SCN lesions on pacemaker properties were observed, these effects were not different in hamsters receiving right- or left-side lesions. More specifically: (1) free-running period (τ) in constant light was shorter in lesioned hamsters irrespective of the side lesioned (Fig. 3a), and the total amount of SCN destruction was found to correlate with τ (Fig. 4). (2) Phase-angle difference (Ψ) of some lesioned hamsters (both right- and left-side) during entrainment to L∶D, 14∶10 was significantly more positive than that of controls (Fig. 3b). (3) The rate of phase-shift following a shift of the light/dark cycle was not different in hamsters with right- or left-side lesions (Fig. 3c). And (4) the simultaneous expression of different circadian periods, similar to ‘splitting’, was observed in hamsters with unilateral lesions (Fig. 5). It is concluded that the right and left SCN are similar in their contributions to the control of circadian rhythmicity and that there is as yet no evidence for the permanent loss of multioscillator properties resulting from the destruction of only one of the two SCN.