Daily rhythms of native Brazilians in summer and winter

Access to electricity, granting relative independence of human activity on the dark phase of the day, has been pointed out as an important cause for the absence of seasonal changes in the daily rhythms of humans living in urban areas. Featuring a population of adult Guarani natives living without access to electricity, the present naturalistic study was designed to explore possible effects of different natural photoperiods and temperature on human circadian rhythms. We compared time series of wrist temperature (WT) and motor activity in winter and summer, respectively, 01 24 individuals aged 18 to 80. Twenty-four-hour rhythms of WT showed lower amplitudes and higher mean levels in summer, with no significant seasonal differences in acrophase. In contrast, rest-activity (RA) rhythms exhibited a significantly later rest on-and offset in summer, but no seasonal changes in duration, amplitude and mean level. We furthermore identified a phase advance of both the WT acrophase and rest onset with increasing age of the individuals. We concluded that in our study the effect of different seasons was reflected in the amplitude and mean level of the WT rhythm, as well the onset of nighttime rest, which was delayed in summer. (C) 2011 Elsevier Inc. All rights reserved.

Daily rhythm of salivary IL-1 beta, cortisol and melatonin in day and night workers

Shiftwork-induced sleep deprivation and circadian disruption probably leads to an increase in the production of cytokines and dysregulation of innate immune system, respectively. This project aims evaluating changes in salivary IL-1 beta, cortisol, and melatonin in night workers. Method. Two day and three night healthy workers participated in this study. Sleep was evaluated by actimetry and activity protocols. Saliva was collected at waking and bedtime the last workday and the following two days-off and was analyzed by ELISA. Results. Neither sleep duration nor efficiency showed any association with salivary IL-1beta. IL-1beta levels were higher at waking than at bedtime during working days for all workers, but only one day and one night-worker maintained this pattern and hormone rhythms during days off. For this night worker, melatonin levels were shifted to daytime. A second one presented clear alterations in IL-1beta and hormone rhythms on days-off. Conclusions. Our preliminary results suggest that night work can disturb the variation pattern of salivary IL-1beta. No association of this variation with sleep was observed. It seems that disruption in hormone rhythms interfere with salivary IL-1beta production. IL-1beta production pattern seems to be maintained when rhythms are present, in spite of a shift in melatonin secretion.

Sleep disorders in climacteric women

Introduction: This paper examines the various factors that contribute to the occurrence of sleep alterations during peri and post climacteric and thus produce significant imperil to women's quality of life. Among the probable causes of insomnia or sleep disorders associated to climacteric stand out the occurrence of vasomotor symptoms, depressive state and respiratory distress during sleep, such as sleep apnea, along with chronic pain, although psychosocial factors related to the climacteric bear major influence on such clinical status. Method: The bibliographic analysis was carried out using several electronic data base namely: Cochrane, Medline, Embase, Bni Plus, Biological Abstracts, Psycinfo, Web Of Science, Sigle, Dissertation Abstracts and ZETOC published in English, Spanish and Poruguese. The key terms used were: sleep, REM sleep, slow wave sleep polysomnography; electroencephalogram; sleep disturbances; disturbances of sleep onset and maintenance; excessive somnolence disturbances; climacteric; menopause; depression; neurobiology; biologic models; circadian rhythm; mental health and epidemiology. Case studies and letters to the editor were excluded. The summaries of the identified studies found in the data base were analyzed and assessed, and the data analyzed separately according to the subjective or objective criteria for data collection. Results: The climacteric transition constitutes a period of major risk for the development of depressive, vasomotor and insomnia symptoms although not caused solely by hypoestrogenism. The diagnostic methods used in the study of sleep disorders range from subjective assessment by means of response to specific questionnaires to the objective analysis of actigraphic or polissonographic daytime and nocturnal reports. Polissonographic studies of the whole night, performed at the laboratory, are the golden method of choice for diagnostic of sleep disorders. Studies point to the high prevalence of sleep disorders in the climacteric, especially insomnia, apnea and periodic movement of legs and also to the fact that this phase of life presents decrease in the quality of sleep. Women in peri and post climacteric show higher sleep latency and difficulty in its maintenance and refer being less satisfied with its quality even when compared to those who are not climacteric. Exception made to the vasomotor symptomatology, the other climacteric complaints such as mood disturbances, libido alterations, cognitive deficit, articular pain and sleep disorders are markedly associated to psychosocial factors, lifestyle and especially to women's perception of what the climacteric means to their lives. Conclusion: The analysis of the available studies revealed a proneness to deterioration of quality of life of climacteric women markedly in the sleep disturbances, depressed mood and anxiety domains and should not to be basically attributed to the climacteric. It is necessary that the professionals consider the need of assessment of such pathologies as complex phenomena and the literature lacks studies contemplating such dimensions.

Field and Laboratory Studies Provide Insights into the Meaning of Day-Time Activity in a Subterranean Rodent (Ctenomys aff. knighti), the Tuco-Tuco

South American subterranean rodents (Ctenomys aff. knighti), commonly known as tuco-tucos, display nocturnal, wheel-running behavior under light-dark (LD) conditions, and free-running periods >24 h in constant darkness (DD). However, several reports in the field suggested that a substantial amount of activity occurs during daylight hours, leading us to question whether circadian entrainment in the laboratory accurately reflects behavior in natural conditions. We compared circadian patterns of locomotor activity in DD of animals previously entrained to full laboratory LD cycles (LD12:12) with those of animals that were trapped directly from the field. In both cases, activity onsets in DD immediately reflected the previous dark onset or sundown. Furthermore, freerunning periods upon release into DD were close to 24 h indicating aftereffects of prior entrainment, similarly in both conditions. No difference was detected in the phase of activity measured with and without access to a running wheel. However, when individuals were observed continuously during daylight hours in a semi-natural enclosure, they emerged above-ground on a daily basis. These day-time activities consisted of foraging and burrow maintenance, suggesting that the designation of this species as nocturnal might be inaccurate in the field. Our study of a solitary subterranean species suggests that the circadian clock is entrained similarly under field and laboratory conditions and that day-time activity expressed only in the field is required for foraging and may not be time-dictated by the circadian pacemaker.

Activity, movement and secretive behavior of a threatened arboreal folivore, the thin-spined porcupine, in the Atlantic forest of southern Bahia, Brazil

Activity and behavior patterns are important components of a given species ecological strategy, as they have profound implications for its survival and reproduction. Here, we studied the activities, movements and secretive behavior of the thin-spined porcupine Chaetomys subspinosus (Rodentia: Erethizontidae), a threatened arboreal folivore in the Brazilian Atlantic rainforest. We aimed to ascertain the behavioral strategies used by this species as well as its responses to seasonal and daily climatic changes. Four radio-collared individuals were followed continuously for 72-h in the summer and winter, as well as during 146 half-night sessions conducted from April 2005 to September 2006 in forest remnants in southern Bahia. The thin-spined porcupines were nocturnally active (17:30-05:40 h), with peaks in activity and movement from 19:00 to 20:00 h and 03:00 to 04:00 h. Animals followed a circadian rhythm of activity during both the summer and winter. During the diel cycle, porcupines spent 74% of their time resting, 14% feeding, 11% traveling and 2% performing other activities. Distance traveled during the diel cycle averaged 277.5 +/- 117.9 m sd. The mean movement rate during the night was 21.6 +/- 30.1 m/h sd. No significant changes in activity budget or daily distance traveled were observed between seasons, most likely in response to the low fluctuations in climatic conditions and food availability throughout the year in the study region. However, rainfall reduced the time that the animals spent on feeding activities and explained day-to-day differences in activity budgets. We also provide details about intraspecific interactions and defecation behavior. Our observations confirmed that thin-spined porcupines, similar to other folivorous species, present low activity levels and short daily movements, and have adopted various cryptic habits, such as nocturnality, a solitary lifestyle, the tendency to leave offspring alone most of the time and defecation in concealed latrines.

Retinal projections and neurochemical characterization of the pregeniculate nucleus of the common marmoset (Callithrix jacchus)

In mammals, the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) are the main components of the circadian timing system. The SCN is the site of the endogenous biological clock that generates rhythms and synchronizes them to environmental cues. The IGL is a key structure that modulates SCN activity and is responsible for the transmission of non-photic information to the SCN, thus participating in the integration between photic and non-photic stimuli. Both the SCN and IGL receive projections of retinal ganglion cells and the IGL is connected to the SCN through the geniculohypothalamic tract. Little is known about these structures in the primate brain and the pregeniculate nucleus (PGN) has been suggested to be the primate equivalent of the rodent IGL. The aim of this study was to characterize the PGN of a primate, the common marmoset (Callithrix jacchus), and to analyze its retinal afferents. Here, the marmoset PGN was found to be organized into three subsectors based on neuronal size, pattern of retinal projections, and the distribution of neuropeptide Y-, GAD-, serotonin-, enkephalin- and substance P-labeled terminals. This pattern indicates that the marmoset PGN is equivalent to the IGL. This detailed description contributes to the understanding of the circadian timing system in this primate species considering the importance of the IGL within the context of circadian regulation. (C) 2012 Elsevier B.V. All rights reserved.

Body weight, metabolism and clock genes

Biological rhythms are present in the lives of almost all organisms ranging from plants to more evolved creatures. These oscillations allow the anticipation of many physiological and behavioral mechanisms thus enabling coordination of rhythms in a timely manner, adaption to environmental changes and more efficient organization of the cellular processes responsible for survival of both the individual and the species. Many components of energy homeostasis exhibit circadian rhythms, which are regulated by central (suprachiasmatic nucleus) and peripheral (located in other tissues) circadian clocks. Adipocyte plays an important role in the regulation of energy homeostasis, the signaling of satiety and cellular differentiation and proliferation. Also, the adipocyte circadian clock is probably involved in the control of many of these functions. Thus, circadian clocks are implicated in the control of energy balance, feeding behavior and consequently in the regulation of body weight. In this regard, alterations in clock genes and rhythms can interfere with the complex mechanism of metabolic and hormonal anticipation, contributing to multifactorial diseases such as obesity and diabetes. The aim of this review was to define circadian clocks by describing their functioning and role in the whole body and in adipocyte metabolism, as well as their influence on body weight control and the development of obesity.

The expression of melanopsin and clock genes in Xenopus laevis melanophores and their modulation by melatonin

Vertebrates have a central clock and also several peripheral clocks. Light responses might result from the integration of light signals by these clocks. The dermal melanophores of Xenopus laevis have a photoreceptor molecule denominated melanopsin (OPN4x). The mechanisms of the circadian clock involve positive and negative feedback. We hypothesize that these dermal melanophores also present peripheral clock characteristics. Using quantitative PCR, we analyzed the pattern of temporal expression of Opn4x and the clock genes Per1, Per2, Bmal1, and Clock in these cells, subjected to a 14-h light:10-h dark (14L:10D) regime or constant darkness (DD). Also, in view of the physiological role of melatonin in the dermal melanophores of X. laevis, we determined whether melatonin modulates the expression of these clock genes. These genes show a time-dependent expression pattern when these cells are exposed to 14L:10D, which differs from the pattern observed under DD. Cells kept in DD for 5 days exhibited overall increased mRNA expression for Opn4x and Clock, and a lower expression for Per1, Per2, and Bmal1. When the cells were kept in DD for 5 days and treated with melatonin for 1 h, 24 h before extraction, the mRNA levels tended to decrease for Opn4x and Clock, did not change for Bmal1, and increased for Per1 and Per2 at different Zeitgeber times (ZT). Although these data are limited to one-day data collection, and therefore preliminary, we suggest that the dermal melanophores of X. laevis might have some characteristics of a peripheral clock, and that melatonin modulates, to a certain extent, melanopsin and clock gene expression.

Daily cycling of nitric oxide synthase (NOS) in the hippocampus of pigeons (C. livia)

Abstract: Background: Nitric oxide synthase (NOS) is essential for the synthesis of nitric oxide (NO), a non-conventional neurotransmitter with an important role in synaptic plasticity underlying processes of hippocampus-dependent memory and in the regulation of biological clocks and circadian rhythms. Many studies have shown that both the NOS cytosolic protein content and its enzymatic activity present a circadian variation in different regions of the rodent brain, including the hippocampus. The present study investigated the daily variation of NOS enzymatic activity and the cytosolic content of nNOS in the hippocampus of pigeons. Results: Adult pigeons kept under a skeleton photoperiod were assigned to six different groups. Homogenates of the hippocampus obtained at six different times-of-day were used for NOS analyses. Both iNOS activity and nNOS cytosolic protein concentrations were highest during the subjective light phase and lowest in the subjective dark phase of the circadian period. ANOVA showed significant time differences for iNOS enzymatic activity (p < 0.05) and for nNOS protein content (p < 0.05) in the hippocampus. A significant daily rhythm for both iNOS and nNOS was confirmed by analysis with the Cosinor method (p < 0.05). The present findings indicate that the enzymatic activity of iNOS and content of nNOS protein in the hippocampus of pigeons exhibit a daily rhythm, with acrophase values occurring during the behavioral activity phase. Conclusions: The data corroborate the reports on circadian variation of NOS in the mammalian hippocampus and can be considered indicative of a dynamic interaction between hippocampus-dependent processes and circadian clock mechanisms.

Melatonin acts through MT1/MT2 receptors to activate hypothalamic Akt and suppress hepatic gluconeogenesis in rats

Melatonin can contribute to glucose homeostasis either by decreasing gluconeogenesis or by counteracting insulin resistance in distinct models of obesity. However, the precise mechanism through which melatonin controls glucose homeostasis is not completely understood. Male Wistar rats were administered an intracerebroventricular (icv) injection of melatonin and one of following: an icv injection of a phosphatidylinositol 3-kinase (PI3K) inhibitor, an icv injection of a melatonin receptor (MT) antagonist, or an intraperitoneal (ip) injection of a muscarinic receptor antagonist. Anesthetized rats were subjected to pyruvate tolerance test to estimate in vivo glucose clearance after pyruvate load and in situ liver perfusion to assess hepatic gluconeogenesis. The hypothalamus was removed to determine Akt phosphorylation. Melatonin injections in the central nervous system suppressed hepatic gluconeogenesis and increased hypothalamic Akt phosphorylation. These effects of melatonin were suppressed either by icv injections of PI3K inhibitors and MT antagonists and by ip injection of a muscarinic receptor antagonist. We conclude that melatonin activates hypothalamus-liver communication that may contribute to circadian adjustments of gluconeogenesis. These data further suggest a physiopathological relationship between the circadian disruptions in metabolism and reduced levels of melatonin found in type 2 diabetes patients.

Daily cycling of nitric oxide synthase (NOS) in the hippocampus of pigeons (C. livia)

Background: Nitric oxide synthase (NOS) is essential for the synthesis of nitric oxide (NO), a non-conventional neurotransmitter with an important role in synaptic plasticity underlying processes of hippocampus-dependent memory and in the regulation of biological clocks and circadian rhythms. Many studies have shown that both the NOS cytosolic protein content and its enzymatic activity present a circadian variation in different regions of the rodent brain, including the hippocampus. The present study investigated the daily variation of NOS enzymatic activity and the cytosolic content of nNOS in the hippocampus of pigeons. Results: Adult pigeons kept under a skeleton photoperiod were assigned to six different groups. Homogenates of the hippocampus obtained at six different times-of-day were used for NOS analyses. Both iNOS activity and nNOS cytosolic protein concentrations were highest during the subjective light phase and lowest in the subjective dark phase of the circadian period. ANOVA showed significant time differences for iNOS enzymatic activity (p < 0.05) and for nNOS protein content (p < 0.05) in the hippocampus. A significant daily rhythm for both iNOS and nNOS was confirmed by analysis with the Cosinor method (p < 0.05). The present findings indicate that the enzymatic activity of iNOS and content of nNOS protein in the hippocampus of pigeons exhibit a daily rhythm, with acrophase values occurring during the behavioral activity phase. Conclusions: The data corroborate the reports on circadian variation of NOS in the mammalian hippocampus and can be considered indicative of a dynamic interaction between hippocampus-dependent processes and circadian clock mechanisms.

Intrinsic organization of the suprachiasmatic nucleus in the capuchin monkey

The suprachiasmatic nucleus (SCN), which is the main circadian biological clock in mammals, is composed of multiple cells that function individually as independent oscillators to express the self-sustained mRNA and protein rhythms of the so-called clock genes. Knowledge regarding the presence and localization of the proteins and neuroactive substances of the SCN are essential for understanding this nucleus and for its successful manipulation. Although there have been advances in the investigation of the intrinsic organization of the SCN in rodents, little information is available in diurnal species, especially in primates. This study, which explores the pattern of expression and localization of PER2 protein in the SCN of capuchin monkey, evaluates aspects of the circadian system that are common to both primates and rodents. Here, we showed that PER2 protein immunoreactivity is higher during the light phase. Additionally, the complex organization of cells that express vasopressin, vasoactive intestinal polypeptide, neuron-specific nuclear protein, calbindin and calretinin in the SCN, as demonstrated by their immunoreactivity, reveals an intricate network that may be related to the similarities and differences reported between rodents and primates in the literature.

Norepinephrine activates NF-κB transcription factor in cultured rat pineal gland

AIMS: The circadian rhythm in mammalian pineal melatonin secretion is modulated by norepinephrine (NE) released at night. NE interaction with β1-adrenoceptors activates PKA that phosphorylates the transcription factor CREB, leading to the transcription and translation of the arylalkylamine-N-acetyltransferase (AANAT) enzyme. Several studies have reported the interplay between CREB and the nuclear factor-κB (NF-κB) and a circadian rhythm for this transcription factor was recently described in the rat pineal gland. In this work we studied a direct effect of NE on NF-κB activation and the role played by this factor on melatonin synthesis and Aanat transcription and activity. MAIN METHODS: Cultured rat pineal glands were incubated in the presence of two different NF-κB inhibitors, pyrrolidine-dithiocarbamate or sodium salicylate, and stimulated with NE. Melatonin content was quantified by HPLC with electrochemical detection. AANAT activity was measured by a radiometric assay and the expression of Aanat mRNA was analyzed by real-time PCR. Gel shift assay was performed to study the NF-κB activation in cultured rat pineal glands stimulated by NE. KEY FINDINGS: Our results showed that the p50/p50 homodimer of NF-κB is activated by NE and that it has a role in melatonin synthesis, acting on Aanat transcription and activity. SIGNIFICANCE: Here we present evidence that NF-κB is an important transcription factor that acts, directly or indirectly, on Aanat transcription and activity leading to a modulation of melatonin synthesis. NE plays a role in the translocation of NF-κB p50/p50 homodimer to the nucleus of pinealocytes, thus probably influencing the nocturnal pineal melatonin synthesis

L'influenza del sonno sull'andamento temporale della consolidazione delle abilità procedurali

Background: It is well known, since the pioneristic observation by Jenkins and Dallenbach (Am J Psychol 1924;35:605-12), that a period of sleep provides a specific advantage for the consolidation of newly acquired informations. Recent research about the possible enhancing effect of sleep on memory consolidation has focused on procedural memory (part of non-declarative memory system, according to Squire’s taxonomy), as it appears the memory sub-system for which the available data are more consistent. The acquisition of a procedural skill follows a typical time course, consisting in a substantial practice-dependent learning followed by a slow, off-line improvement. Sleep seems to play a critical role in promoting the process of slow learning, by consolidating memory traces and making them more stable and resistant to interferences. If sleep is critical for the consolidation of a procedural skill, then an alteration of the organization of sleep should result in a less effective consolidation, and therefore in a reduced memory performance. Such alteration can be experimentally induced, as in a deprivation protocol, or it can be naturally observed in some sleep disorders as, for example, in narcolepsy. In this research, a group of narcoleptic patients, and a group of matched healthy controls, were tested in two different procedural abilities, in order to better define the size and time course of sleep contribution to memory consolidation. Experimental Procedure: A Texture Discrimination Task (Karni & Sagi, Nature 1993;365:250-2) and a Finger Tapping Task (Walker et al., Neuron 2002;35:205-11) were administered to two indipendent samples of drug-naive patients with first-diagnosed narcolepsy with cataplexy (International Classification of Sleep Disorder 2nd ed., 2005), and two samples of matched healthy controls. In the Texture Discrimination task, subjects (n=22) had to learn to recognize a complex visual array on the screen of a personal computer, while in the Finger Tapping task (n=14) they had to press a numeric sequence on a standard keyboard, as quickly and accurately as possible. Three subsequent experimental sessions were scheduled for each partecipant, namely a training session, a first retrieval session the next day, and a second retrieval session one week later. To test for possible circadian effects on learning, half of the subjects performed the training session at 11 a.m. and half at 17 p.m. Performance at training session was taken as a measure of the practice-dependent learning, while performance of subsequent sessions were taken as a measure of the consolidation level achieved respectively after one and seven nights of sleep. Between training and first retrieval session, all participants spent a night in a sleep laboratory and underwent a polygraphic recording. Results and Discussion: In both experimental tasks, while healthy controls improved their performance after one night of undisturbed sleep, narcoleptic patients showed a non statistically significant learning. Despite this, at the second retrieval session either healthy controls and narcoleptics improved their skills. Narcoleptics improved relatively more than controls between first and second retrieval session in the texture discrimination ability, while their performance remained largely lower in the motor (FTT) ability. Sleep parameters showed a grater fragmentation in the sleep of the pathological group, and a different distribution of Stage 1 and 2 NREM sleep in the two groups, being thus consistent with the hypothesis of a lower consolidation power of sleep in narcoleptic patients. Moreover, REM density of the first part of the night of healthy subjects showed a significant correlation with the amount of improvement achieved at the first retrieval session in TDT task, supporting the hypothesis that REM sleep plays an important role in the consolidation of visuo-perceptual skills. Taken together, these results speak in favor of a slower, rather than lower consolidation of procedural skills in narcoleptic patients. Finally, an explanation of the results, based on the possible role of sleep in contrasting the interference provided by task repetition is proposed.

Studio dei ritmi circadiani in pazienti in stato vegetativo

Objective: To study circadian rhythms (sleep-wake, body core temperature and melatonin circadian rhythms) in patients in vegetative state (VS) in basal condition and after nocturnal blue light exposure. Methods: Eight patients in VS underwent two experimental sessions of 48 consecutive hours polysomnography with body core temperature (BCT) measurement separated by a 1-week interval. For a week between the two experimental sessions, patients underwent nocturnal blue light exposure (470 nm; 58 μW/cm2 for 4 hours from 11.30 p.m. to 3.30 a.m.). Brain MRI, Level of Cognitive Functioning Scale (LCF) and Disability Rating Scale (DRS) were assessed just before polysomnography. Results: In all patients LCF and DRS confirmed vegetative state. All patients showed a sleep-wake cycle. All patients showed spindle or spindle-like activities. REM sleep was detected in only 7 patients. Patients displayed a greater fragmentation of nocturnal sleep due to frequent awakenings. Mean nocturnal sleep efficiency was significantly reduced (40±22 vs. 74±17) in VS patients respect to controls. A significantly increasing of phase 1 and a significantly reduction of phase 2 and phase 3 were observed too. A modification of diurnal sleep total time and of diurnal duration of REM sleep were found after 1-week nocturnal blue light exposure. All patients displayed a normal BCT 24-h rhythm in basal condition and after nocturnal blue light exposure. A reduction of mean nocturnal melatonin levels in basal condition were observed in VS patients. Melatonin suppression after blue light exposure was observed in only 2 patients in VS. Conclusions: We found disorganized sleep-wake cycle and a normal BCT rhythm in our patients in VS. A reduction of mean nocturnal melatonin levels in basal condition were observed too.