Absence Of Circadian Rhythm Research Articles

Absence of Circadian Rhythm in Fecal Microbiota of Laying Hens under Common Light.

Simple SummaryThe circadian rhythm of gut microbiota is an important biological rhythm that plays a crucial role in host health. This study showed that the defecation time may be an important factor in the diversity, proportion, and functions of the feces microbial community. However, there was no circadian rhythm of microbial community assembly confirmed by JTK_Cycle analysis, which is a tool for identifying and characterizing oscillations and can efficiently identify and characterize cycling variables in large data sets. These results might suggest there was no obvious circadian rhythm of fecal microbiota in laying hens under common light.The circadian rhythm of gut microbiota is an important biological rhythm that plays a crucial role in host health. However, few studies have determined the associations between the circadian rhythm and gut microbiota in laying hens. The present experiment investigated the circadian rhythm of fecal microbiota in laying hens. Feces samples were collected from 10 laying hens at nine different time points (06:00–12:00–18:00–00:00–06:00–12:00–18:00–00:00–06:00) to demonstrate the circadian rhythm of fecal microbiota. The results showed that the α and β diversity of the fecal microbiota fluctuated significantly at different time points. Beta nearest taxon index analysis suggested that assembly strategies of the abundant and rare amplicon sequence variant (ASV) sub-communities were different. Abundant ASVs preferred dispersal limitation (weak selection), and rare ASVs were randomly formed due to the “non-dominant” fractions. Highly robust fluctuations of fecal microbiota at the phylum level were found. For example, Firmicutes and Proteobacteria fluctuated inversely to each other, but the total ratio remained in a dynamic balance over 48 h. We identified that temporal dynamic changes had a significant effect on the relative abundance of the important bacteria in the feces microbial community using the random forest algorithm. Eight bacteria, Ruminococcus gnavus, Faecalibacterium, Ruminococcaceae, Enterococcus cecorum, Lachnospiraceae, Clostridium, Clostridiales, and Megamonas, showed significant changes over time. One unexpected finding was the fact that these eight bacteria belong to Firmicutes. The pathways showed significant fluctuation, including xenobiotic biodegradation and metabolism, carbohydrate metabolism, and amino acid metabolism, which were consistent with the metabolic functions of amino acids and carbohydrates from the feed. This study showed that the defecation time may be an important factor in the diversity, proportion, and functions of the feces microbial community. However, there was no circadian rhythm of microbial community assembly confirmed by JTK_Cycle analysis. These results might suggest there was no obvious circadian rhythm of fecal microbiota in laying hens under common light.

Spaceflight-induced neuroplasticity in humans as measured by MRI: what do we know so far?

Space travel poses an enormous challenge on the human body; microgravity, ionizing radiation, absence of circadian rhythm, confinement and isolation are just some of the features associated with it. Obviously, all of the latter can have an impact on human physiology and even induce detrimental changes. Some organ systems have been studied thoroughly under space conditions, however, not much is known on the functional and morphological effects of spaceflight on the human central nervous system. Previous studies have already shown that central nervous system changes occur during and after spaceflight in the form of neurovestibular problems, alterations in cognitive function and sensory perception, cephalic fluid shifts and psychological disturbances. However, little is known about the underlying neural substrates. In this review, we discuss the current limited knowledge on neuroplastic changes in the human central nervous system associated with spaceflight (actual or simulated) as measured by magnetic resonance imaging-based techniques. Furthermore, we discuss these findings as well as their future perspectives, since this can encourage future research into this delicate and intriguing aspect of spaceflight. Currently, the literature suffers from heterogeneous experimental set-ups and therefore, the lack of comparability of findings among studies. However, the cerebellum, cortical sensorimotor and somatosensory areas and vestibular-related pathways seem to be involved across different studies, suggesting that these brain regions are most affected by (simulated) spaceflight. Extending this knowledge is crucial, especially with the eye on long-duration interplanetary missions (e.g. Mars) and space tourism.

Depression-like behaviour in mice is associated with disrupted circadian rhythms in nucleus accumbens andperiaqueductal grey.

An association between circadian rhythms and mood regulation is well established, and disturbed circadian clocks are believed to contribute to the development of mood disorders, including major depressive disorder. The circadian system is coordinated by the suprachiasmatic nucleus (SCN), the master pacemaker in the hypothalamus that receives light input from the retina and synchronizes circadian oscillators in other brain regions and peripheral tissues. Lacking the tight neuronal network that couples single-cell oscillators in the SCN, circadian clocks outside the SCN may be less stable and more susceptible to disturbances, for example by clock gene mutations or uncontrollable stress. However, non-SCN circadian clocks have not been studied extensively in rodent models of mood disorders. In the present study, it was hypothesized that disturbances of local circadian clocks in mood-regulating brain areas are associated with depression-like behaviour in mice. Using the learned helplessness procedure, depression-like behaviour was evoked in mice bearing the PER2::LUC circadian reporter, and then circadian rhythms of PER2 expression were examined in brain slices from these mice using luminometry and bioluminescence imaging. It was found that helplessness is associated with absence of circadian rhythms in the nucleus accumbens and the periaqueductal grey, two of the most critical brain regions within the reward circuit. The current study provides evidence that susceptibility of mice to depression-like behaviour is associated with disturbed local circadian clocks in a subset of mood-regulating brain areas, but the direction of causality remains to be determined.

Abstract 1515: Disruption of circadian rhythmicity in liver metastasis of colorectal cancer

Abstract Background: Liver metastases of colorectal cancer are a major cause of cancer related mortality. Resection of hepatic metastasis prolongs life, but 25% of the functional reserve of the liver should remain after resection to allow adequate liver regeneration. An effective means to downsize the tumor and enable resection is the use of chemotherapeutics. Efficacy and adverse side effects of chemotherapy may vary considerably over a 24 hour period. Chronotherapy (circadian rhythm adjusted chemotherapy) could take advantage of the fact that there may be asynchronies in circadian rhythm between normal and cancer tissue. In addition, genetic or functional disruption of the circadian clock may result in genomic instability and accelerated carcinogenisis and tumor growth. A more thorough understanding of circadian rhytmicity may help in elucidating the role of the clock in tumorigenesis and tumor growth and develop more effective chronotherapeutic chemotherapy treatment schedules. Therefore, in this study we investigated the 24-hour expression levels of key circadian clock genes in colorectal liver metastasis and adjacent healthy liver tissue in the mouse. Materials and methods: Male BALB/c mice were injected with C26 colorectal carcinoma cells into the spleen. Three weeks after tumor inoculation, a hepatectomy was performed at 6 different timepoints over a 24-hour period (n=4 per timepoint) to compare circadian rhythmicity in tumor and adjacent healthy tissue. RNA was isolated and RT-PCR was performed on 5 clock genes: Rev-erbα, Per2, Per1, DBP, and Bmal1 and a clock independent gene induced by feeding (Acss2). Results: Healthy liver tissue showed normal 24-hour oscillations of all 5 clock genes, consistent with normal circadian rhytmicity. In colorectal liver metastasis however, 24-hour oscillations were completely absent in all clock genes except Per2. Per2 oscillations were similar in tumor and adjacent liver tissue, although expression levels in tumor tissue were lower. Since Per2 may also be induced by feeding, we determined the expression of the food induced gene Acss2, which is independent of circadian rhythm. Acss2 levels rose in response to feeding, followed by a rise in Per2, strongly suggesting that the increased expression of Per2 was induced by feeding. Conclusion: Our data demonstrate the absence of circadian rhythm in hepatic metastasis of C26 coloncarcinoma in vivo. The difference between tumor and healthy tissue in this model may provide new clues to further understand the biology, and optimize treatment of hepatic metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1515. doi:10.1158/1538-7445.AM2011-1515

Autonomic Neurocardiac Dysregulation in R6/1 Huntington's Disease Transgenic Mice

Huntington’s disease (HD) is a heritable neurodegenerative disorder. While heart disease has been attributed as one of the major causes of death in HD patients, it has not been characterised. In addition, abnormal activity of the autonomic nervous system (ANS) has been reported in HD patients yet the potential cardiac consequences are unclear. Using the R6/1 mouse model of HD expressing a mutant human huntingtin gene, we studied the cardiac phenotype from pre-HD (3-mo) to advanced-HD (7-mo). HD mice exhibited a modest reduction in heart mass and cardiomyocyte size compared to wild-type (WT) littermates. Baseline cardiac function was preserved, even in seven month-old HD mice. ECG recordings revealed that from pre-HD phase HD mice had: (1) absence of circadian rhythm in heart rate, (2) marked instability in R–R intervals, which was normalised by atropine and (3) different forms of arrhythmias such as A–V conduction blockade, supra-ventricular ectopic beats, ventricular tachycardia, and short episodes of atrial fibrillation. Fur195 Cardiac Chamber Specific Gene Delivery Using AdenoAssociated Virus 2/9

P.2.a.014 Rapid effect of escitalopram in a behavioural model of depression: the chronic escape deficit

The chronobiological circadian behaviour in serum levels of β-microglobulin has been investigated in three groups of subjects: (A) 6 healthy controls; (B) 6 patients with untreated multiple myeloma; (C) 6 patients with multiple myeloma in complete remission after polychemotherapy. From all subjects, under the same standard life conditions, venous blood samples were drawn at 4-hour intervals starting from midnight during the span of a whole day. Circulating serum β2-microglobulin levels were determined by RIA method. The time-related data were analyzed by chronograms and the “mean-group cosinor” method. A significant circadian rhythm for serum β2-microglobulin was detected in the control group, with a peak in the morning hours, and in untreated patients, with a peak in the afternoon hours. No significant rhythm was found in treated patients with multiple myeloma. A significant mesor reduction was noted in patients with complete remission, correlated with the absence of circadian rhythm, in respect to untreated patients. These data suggests that serum levels of β2-microglobulin could be related to the neoplastic plasma cell proliferation and to the effect of therapy, and that the circadian evaluation could be used as a guide in monitoring myeloma patients.

Circadian Rhythms in Infants

After completing this article, readers should be able to: 1. Describe how circadian rhythms are generated. 2. Describe how lighting influences the circadian system. 3. Delineate the period during which the origin of circadian rhythms develops. 4. Describe the relationship between maternal circadian rhythms and the development of circadian rhythms in infants. 5. Characterize the potential sequelae of impaired fetal and early neonatal circadian rhythms related to sleep patterns. 6. Describe beneficial lighting patterns for preterm infants in the neonatal intensive care nursery. Circadian rhythms are endogenously generated rhythms that have a period length of about 24 hours. Evidence gathered over the past decade indicates that the circadian timing system develops prenatally, with the suprachiasmatic nuclei (SCN) in the anterior hypothalamus, the site of a circadian clock, present by mid-gestation in primates. Recent evidence also shows that the circadian system of primate infants is responsive to light at very early stages (as early as 25 to 28 weeks’ gestation in humans) and that low-intensity lighting can regulate the developing clock. After birth, circadian system outputs mature progressively, with rhythms in sleep-wake cycles, body temperature, and hormone production generally developing between 1 and 3 months of age. The importance of light in regulation of circadian rhythm in infants is highlighted by the early establishment of rest-activity patterns that are in phase with the 24-hour light-dark cycle in preterm infants exposed to low-intensity cycled lighting. With the continued elucidation of circadian system development and influences on human physiology and illness, it is anticipated that consideration of circadian biology will become an increasingly important component of neonatal care. ### The Circadian Timing System Notable examples of circadian rhythms include the sleep-wake cycle and daily rhythms in body temperature and hormone production. Circadian rhythms are also involved in the pathogenesis of illnesses, such as reactive airway disease (eg, asthma) and myocardial infarction. The system responsible …

The Suprachiasmatic Nucleus Is Essential for Circadian Body Temperature Rhythms in Hibernating Ground Squirrels

Body temperature (T(b)) was recorded at 10 min intervals over 2.5 years in female golden-mantled ground squirrels that sustained complete ablation of the suprachiasmatic nucleus (SCNx). Animals housed at an ambient temperature (T(a)) of 6.5 degrees C were housed in a 12 hr light/dark cycle for 19 months followed by 11 months in constant light. The circadian rhythm of T(b) was permanently eliminated in euthermic and torpid SCNx squirrels, but not in those with partial destruction of the SCN or in neurologically intact control animals. Among control animals, some low-amplitude T(b) rhythms during torpor were driven by small (<0.1 degrees C) diurnal changes in T(a). During torpor bouts in which T(b) rhythms were unaffected by T(a), T(b) rhythm period ranged from 23.7 to 28.5 hr. Both SCNx and control squirrels were more likely to enter torpor at night and to arouse during the day in the presence of the light/dark cycle, whereas entry into and arousal from torpor occurred at random clock times in both SCNx and control animals housed in constant light. Absence of circadian rhythms 2.5 years after SCN ablation indicates that extra-SCN pacemakers are unable to mediate circadian organization in euthermic or torpid ground squirrels. The presence of diurnal rhythms of entry into and arousal from torpor in SCNx animals held under a light/dark cycle, and their absence in constant light, suggest that light can reach the retina of hibernating ground squirrels maintained in the laboratory and affect hibernation via an SCN-independent mechanism.

Influence of Pulsatile and Nonpulsatile Left Heart Bypass on the Hormonal Circadian Rhythm

We investigated endocrine circadian rhythm (CR) during pulsatile and nonpulsatile left heart bypass (PLHB and NLHB). A ventricular assist device (VAD) was installed in five goats. After 2 weeks of PLHB, NLHB was subsequently conducted for 4 weeks. The levels of melatonin, cortisol, and renin activity were measured every 2 hours for 24 hours on the last day of the second PLHB week and the second and fourth NLHB weeks. Acquired data were compared with those of the normal control goats (Cont) to determine the presence or absence of CR, as well as the timing, acrophase, amplitude, and mesor of CR. Variations in melatonin, CR were consistently detected at all sampling points. In contrast, CR of cortisol during PLHB and NLHB was observed in a few cases, although considerable CR was noted in most of the Cont cases. The variations in renin activity indicated CR in most of the Cont cases and in all cases at all sampling points during PLHB and NLHB, whereas their acrophases were diversified. In conclusion, the CR of melatonin, reflecting the fundamental circadian clock, was maintained during both PLHB and NLHB, while it could be modified for stress sensitive cortisol and hemodynamic responsive renin during these bypass modalities.

The effects of period mutations and light on the activity rhythms of Drosophila melanogaster.

Strains of Drosophila melanogaster homozygous for alleles of the period gene (perO, perL, perS, and per+) were reared for multiple generations either in light:dark cycles (LD), continuous illumination (LL), or chronic darkness (DD). The locomotor activity of adult flies from these cultures was monitored in either LL or DD. Flies that were reared and tested in DD had a lower proportion of individuals with normal circadian rhythms than flies reared in LD or LL and tested in DD. The activity rhythms of DD-reared DD-tested animals, when present, showed phase coherence within two out of seven populations, while 8 out of 10 LL-reared DD-tested showed phase coherence. Flies tested in LL were largely devoid of circadian rhythms regardless of their rearing environment. Ultradian rhythms were more evident under conditions disruptive to circadian rhythmicity, but were observed in the presence and absence of circadian rhythms. The periods of the ultradian rhythms of LL-reared DD-tested and LD-reared DD-tested flies varied significantly among genotypes, while in other rearing and testing regimes, no relationship was found.

Light-induced suppression of the rat circadian system.

In a constant environment, circadian rhythms persist with slightly altered period lengths. Results of studies with continuous light exposure are less clear, because of short exposure durations and single-variable monitoring. This study sought to characterize properties of the oscillator(s) controlling the rat's circadian system by monitoring both body temperature and locomotor activity. We observed that prolonged exposure of male Sprague-Dawley rats to continuous light (LL) systematically induced complete suppression of body temperature and locomotor activity circadian rhythms and their replacement by ultradian rhythms. This was preceded by a transient loss of coupling between both functions. Continuous darkness (DD) restored circadian synchronization of temperature and activity circadian rhythms within 1 wk. The absence of circadian rhythms in LL coincided with a mean sixfold decrease in plasma melatonin and a marked dampening but no abolition of its circadian rhythmicity. Restoration of temperature and activity circadian rhythms in DD was associated with normalization of melatonin rhythm. These results demonstrated a transient internal desynchronization of two simultaneously monitored functions in the rat and suggested the existence of two or more circadian oscillators. Such a hypothesis was further strengthened by the observation of a circadian rhythm in melatonin, despite complete suppression of body temperature and locomotor activity rhythms. This rat model should be useful for investigating the physiology of the circadian timing system as well as to identify agents and schedules having specific pharmacological actions on this system.

Absence of circadian rhythm in the disposition of melatonin in the cow.

Five adult pasture-bred Prim Holstein cows were used to document the time invariance of melatonin disposition in the cow. Melatonin was administered by an intravenous route as a bolus (5 micrograms/kg of body weight) at either 1430 or 2230. Data were analysed according to a three-compartment open model with melatonin elimination from the central compartment. The mean (+/- SD) kinetic parameters describing melatonin disposition, during day and night, respectively, were plasma clearances: 0.0267 +/- 0.0084 l/kg per min and 0.0229 +/- 0.0031 l/kg per min; steady state volume of distribution: 0.826 +/- 0.229 l/kg and 0.780 +/- 0.193 l/kg; terminal half lives: 58.9 +/- 23.7 min and 64.1 +/- 33.7 min; mean residence times: 32.0 +/- 8.8 min and 33.9 +/- 6.2 min. No statistical difference was found between diurnal and nocturnal values for these parameters. These results support the concept of time invariance for melatonin kinetics in cattle and validate the use of diurnal experiments for the study of melatonin kinetics.

Circadian rhythms of food and water intake and urine excretion in diabetic rats

The light/dark (L/D) rhythms of food and water intake and urine output were studied in normal and diabetic rats for 7 consecutive days at 4-h intervals. The control rats showed the highest values of these parameters during the dark phase (83.68% food, 68.71% water, and 67.44% urine). The diabetic rats also maintained this nocturnal predominance, although the values were less marked (59.55% food, 55% water, and 56% urine). A circadian rhythm of food ( ø = 3.31 h) and water ( ø = 3.54 h) intake as well as of the volume of urine excreted ( ø = 1.10) was detected in the control animals. The diabetic rats, in spite of presenting polyphagia, maintain the circadian rhythm of food intake, whereas a loss of the normal circadian variation of drinking intake was observed as well as the absence of circadian rhythm in urinary excretion. It was concluded that in streptozotocin-diabetic rats we have observed a loss of the normal patterns of water intake and urinary excretion, perhaps masked by the polydipsia and polyuria, whereas the circadian rhythm of food intake remains.

Diurnal variations of serum β2-microglobulin in multiple myeloma

The chronobiological circadian behaviour in serum levels of β-microglobulin has been investigated in three groups of subjects: (A) 6 healthy controls; (B) 6 patients with untreated multiple myeloma; (C) 6 patients with multiple myeloma in complete remission after polychemotherapy. From all subjects, under the same standard life conditions, venous blood samples were drawn at 4-hour intervals starting from midnight during the span of a whole day. Circulating serum β2-microglobulin levels were determined by RIA method. The time-related data were analyzed by chronograms and the “mean-group cosinor” method. A significant circadian rhythm for serum β2-microglobulin was detected in the control group, with a peak in the morning hours, and in untreated patients, with a peak in the afternoon hours. No significant rhythm was found in treated patients with multiple myeloma. A significant mesor reduction was noted in patients with complete remission, correlated with the absence of circadian rhythm, in respect to untreated patients. These data suggests that serum levels of β2-microglobulin could be related to the neoplastic plasma cell proliferation and to the effect of therapy, and that the circadian evaluation could be used as a guide in monitoring myeloma patients.

Circadian rhythms in maternal plasma cortisol and estriol concentrations at 30 to 31, 34 to 35, and 38 to 39 weeks' gestational age

In order to examine the relationship between circadian rhythms in different steroids cortisol and estriol were measured by radioimmunoassay in maternal venous plasma taken at 30- to 60-minute intervals over 24 hours from nine healthy women at 30 to 31, 11 at 34 to 35 and 10 at 38 to 39 weeks' gestation. Maternal cortisol was maximal at 0730 to 0830 hours and fell significantly to its lowest concentration between 1830 and 0130 hours. At 30 to 31 and 34 to 35 weeks there was a significant circadian rhythm in estriol concentrations which was inversely related to the circadian rhythm in cortisol. At 38 to 39 weeks mean estriol concentrations were significantly higher than those at 30 to 31 and 34 to 35 weeks but there was no significant circadian pattern. We concluded that there is an inverse relationship between maternal cortisol and estriol at 30 to 31 and 34 to 35 weeks, which would be consistent with a maternal effect on fetal adrenal function. The increase in mean concentration and absence of circadian rhythm in maternal plasma estriol at term might suggest an additional positive stimulus to fetal adrenal function. The existence of patterns in maternal estriol concentrations must be taken into account in the use of sequential measurements of this hormone during the last 10 weeks of pregnancy.

Probable Pituitary Adenoma with Adrenocorticotropin Hypersecretion (Corticotropinoma) Secondary to Addison's Disease

A 50-yr-old woman with Addison's disease from the age of 14 yr was diagnosed as empty sella turcica in 1974 (Rev Clin Esp 139: 183, 1975). She subsequently continued with hyperpigmentation in spite of adequate hormone substitution therapy which permitted her to lead a normal life. When studied she showed an extreme elevation of plasma ACTH (1500--2000 pg/ml), and with dexamethasone (2 and 8 mg/day) continued to have levels of 900 pg/ml. With 60 mg hydrocortisone daily, effects of overdosage were observed (swelling and Cushingoid facies) associated with depigmentation. However, she continued to manifest levels of plasma ACTH of 700 pg/ml and an absence of circadian rhythm. It seems likely that this patient represents a case of pituitary ACTH secretory adenoma (corticotropinoma) secondary to the preexisting Addison's disease. The circulating levels of other pituitary hormones were normal.