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ABSTRACT: Melatonin is a pleiotropic molecule with many cellular and systemic actions, including chronobiotic effects. Beneficial effects are widely documented concerning the treatment of neoplastic diseases in vivo as well as reductions in viability of cultured cells from melanoma, one of the most aggressive cancers in humans. However, studies of its effects on non-tumor cells in vitro have not focused on viability, except for experiments aiming to protect against oxidotoxicity or other toxicological insults. Furthermore, there is no agreement on the range of effective melatonin concentrations in vitro, and the mechanisms that reduce cell viability have remained unclear. Tumor cell-specific increases in the production of reactive oxygen and nitrogen species (ROS/RNS) may provide a possible explanation. Our aim was to analyze the potential inhibition of tumor (B16 melanoma 4A5) and non-tumor cell (3T3 Swiss albino) viability using a wide range of melatonin concentrations (10-11-10-2 M), and to determine whether intracellular ROS enhancement was involved in this process. In the absence of fetal bovine serum (FBS), low melatonin concentrations (10-9-10-5 M) reduced the proliferation of melanoma cells with no effect in fibroblasts, whereas, in the presence of FBS, they had no effect or even increased the proliferation of both fibroblast and melanoma cells. Melatonin concentrations in the upper millimolar range increased ROS levels and reduced the viability of both cell types, but more markedly so in non-tumor cells. Thus, low melatonin concentrations reduce proliferation in this specific melanoma cell line, whereas high concentrations affect the viability of both tumor (B16 4A5 melanoma) and non-tumor (3T3 fibroblasts) cells. Increased ROS levels in both lines indicate a role for ROS production in the reduction of cell viability at high-but not low-melatonin concentrations, although the mechanism of action still remains to be elucidated.
International Journal of Molecular Sciences 01/2013; 14(2):3901-20. · 2.60 Impact Factor
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ABSTRACT: Most circadian rhythms are controlled by a major pacemaker located in the hypothalamic suprachiasmatic nucleus. Some of these rhythms, called marker rhythms, serve to characterize the timing of the internal temporal order. However, these variables are susceptible to masking effects as the result of activity, body position, light exposure, environmental temperature and sleep. Recently, wrist skin temperature (WT) has been proposed as a new index for evaluating circadian system status. In light of previous evidence suggesting the important relationship between WT and core body temperature regulation, the aim of this work was to purify the WT pattern in order to obtain its endogenous rhythm with the application of multiple demasking procedures. To this end, 103 subjects (18-24 years old) were recruited and their WT, activity, body position, light exposure, environmental temperature and sleep were recorded under free-living conditions for 1 week. WT demasking by categories or intercepts was applied to simulate a "constant routine" protocol (awakening, dim light, recumbent position, low activity and warm environmental temperature). Although the overall circadian pattern of WT was similar regardless of the masking effects, its amplitude was the rhythmic parameter most affected by environmental conditions. The acrophase and mesor were determined to be the most robust parameters for characterizing this rhythm. In addition, a circadian modulation of the masking effect was found for each masking variable. WT rhythm exhibits a strong endogenous component, despite the existence of multiple external influences. This was evidenced by simultaneously eliminating the influence of activity, body position, light exposure, environmental temperature and sleep. We therefore propose that it could be considered a valuable and minimally-invasive means of recording circadian physiology in ambulatory conditions.
PLoS ONE 01/2013; 8(4):e61142. · 4.09 Impact Factor
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ABSTRACT: Alzheimer disease (AD) is a neurodegenerative disorder that primarily causes β-amyloid accumulation in the brain, resulting in cognitive and behavioral deficits. AD patients, however, also suffer from severe circadian rhythm disruptions, and the underlying causes are still not fully known. Patients with AD show reduced systemic melatonin levels. This may contribute to their symptoms, since melatonin is an effective chronobiotic and antioxidant with neuroprotective properties. Here, the authors critically assessed the effects of long-term melatonin treatment on circadian system function, hippocampal oxidative stress, and spatial memory performance in the APPswe/PS1 double transgenic (Tg) mouse model of AD. To test if melatonin MT1/MT2 receptor activation, alone, was involved, the authors chronically treated some mice with the selective MT1/MT2 receptor agonist ramelteon. The results indicate that many of the circadian and behavioral parameters measured, including oxidative stress markers, were not significantly affected in these AD mice. During the day, though, Tg controls (Tg-CON) showed significantly higher mean activity and body temperature (BT) than wild-type (WT) mice. Overall, BT rhythm amplitude was significantly lower in Tg than in WT mice. Although melatonin treatment had no effect, ramelteon significantly reduced the amplitude of the BT rhythm in Tg mice. Towards the end of the experiment, Tg mice treated with ramelteon (Tg-RAM) showed significantly higher circadian rhythm fragmentation than Tg-CON and reduced circadian BT rhythm strength. The free-running period (τ) for the BT and locomotor activity (LA) rhythms of Tg-CON was <24 h. Whereas melatonin maintained τ at 24 h for BT and LA in both genotypes, ramelteon treatment had no effect. In the behavioral tests, the number of approaches and time spent exploring novel objects were significantly higher in Tg-CON than WT controls. Brain tissue analysis revealed significant reduction in hippocampal protein oxidation in Tg-MEL and Tg-RAM compared with Tg-CON animals. These results suggest that not all aspects of the circadian system are affected in the APPswe/PS1 mice. Therefore, care should be taken when extending the results obtained in Tg mice to develop new therapies in humans. This study also revealed the complexity in the therapeutic actions of melatonin and ramelteon in this mouse model of AD.
Chronobiology International 08/2012; 29(7):822-34. · 4.03 Impact Factor
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ABSTRACT: OBJETIVE: The aim of the present work was to investigate associations in circadian markers, melatonin (MT) and cortisol, with metabolic syndrome (MetS) parameters, and with leptin, adiponectin and ghrelin plasma values. METHODS: The study was conducted in 70 women (mean age: 41±10years) that were classified without MetS (n=30) and with MetS (n=40). Blood collection, plasma separation and processing, and biochemical analyses for plasma lipids were performed. For measuring salivary melatonin, participants collected two samples. The first simple was obtained before lunch (at 14:00 p.m.) and the second sample was taken at night (3:00 a.m.). On a random working day, participants delivered repeated salivary cortisol samples. The first sample was obtained in the morning (09:00 a.m.), then before lunch at (14:00 p.m.), and finally just before bedtime (23:00 p.m.). RESULTS: Significant differences were found between the MT measurements taken at night in women without and with MetS. With respect to cortisol, significant differences were found in the different times cortisol levels toward a more flattened pattern among MetS women. Both parameters were positive correlated between them. Of note MT and cortisol night/morning ratios were associated with MetS score and metabolic syndrome components. CONCLUSION: The findings indicate that diminished daily amplitude in MT and cortisol circadian patterns was associated with metabolic disturbances in blood pressure, glucose and plasma lipids regulation, ghrelin and adipocyte-secreted hormones such as leptin and adiponectin.
Physiology & Behavior 06/2012; · 2.87 Impact Factor
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ABSTRACT: Circadian rhythmicity has been widely studied in the cardiovascular system and has a relevant role in three different areas:
heart, vascular smooth muscle, and hemostatic capacity of blood. Metabolic syndrome (MetS) and chronodisruption are also highly
interconnected. Epidemiologic studies show that shift workers and short sleepers develop obesity and MetS impairments more
frequently. In addition, studies performed in experimental models suggest that the circadian clock genes network plays an
important role in mammalian energy balance and demonstrate the implication of the clock genes machinery in MetS. New nutrigenomic
studies indicate that genetic variants of the CLOCK gene are highly associated with cardiovascular risk and MetS features. The timing of antihypertensive therapies should be
also considered to achieve a nocturnal dip in the pattern of blood pressure. Chronotherapy could also be used in MetS treatment,
as the appropriate resetting of the circadian system (ie, “chronoenhancement”) may lead to a reduced incidence of obesity
and MetS.
Current Cardiovascular Risk Reports 04/2012; 4(1):15-23.
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ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disorder that also involves circadian rhythm alterations. Modifications of circadian rhythm parameters have been shown to occur in both PD patients and toxin-induced PD animal models. In the latter case, rotenone, a potent inhibitor of mitochondrial complex I (nicotinamide adenine dinucleotide [NADH]-quinone reductase), has been used to elicit degeneration of dopaminergic neurons and development of parkinsonian syndrome. The present work addresses alterations induced by rotenone on both locomotor and body temperature circadian rhythms in rats. Rotenone-treated rats exhibited abnormalities in equilibrium, postural instability, and involuntary movements. Long-term subcutaneous administration of rotenone significantly reduced mean daily locomotor activity in most animals. During rotenone administration, mean body temperatures (BTs) and BT rhythm amplitudes were significantly lower than those observed in the control group. After long-term rotenone administration, the circadian rhythms of both locomotor activity (LA) and BT displayed decreased amplitudes, lower interdaily phase stability, and higher rhythm fragmentation, as compared to the control rats. The magnitude of the LA and BT circadian rhythm alterations induced by rotenone positively correlated with degree of motor impairment. These results indicate that rotenone induces circadian dysfunction in rats through some of the same mechanisms as those responsible for the development of motor disturbances.
Chronobiology International 03/2012; 29(2):147-56. · 4.03 Impact Factor
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ABSTRACT: Evidence is accumulating regarding the importance of circadian core oscillators, several associated factors, and melatonin signaling in the maintenance of health. Dysfunction of endogenous clocks, melatonin receptor polymorphisms, age- and disease-associated declines of melatonin likely contribute to numerous diseases including cancer, metabolic syndrome, diabetes type 2, hypertension, and several mood and cognitive disorders. Consequences of gene silencing, overexpression, gene polymorphisms, and deviant expression levels in diseases are summarized. The circadian system is a complex network of central and peripheral oscillators, some of them being relatively independent of the pacemaker, the suprachiasmatic nucleus. Actions of melatonin on peripheral oscillators are poorly understood. Various lines of evidence indicate that these clocks are also influenced or phase-reset by melatonin. This includes phase differences of core oscillator gene expression under impaired melatonin signaling, effects of melatonin and melatonin receptor knockouts on oscillator mRNAs or proteins. Cross-connections between melatonin signaling pathways and oscillator proteins, including associated factors, are discussed in this review. The high complexity of the multioscillator system comprises alternate or parallel oscillators based on orthologs and paralogs of the core components and a high number of associated factors with varying tissue-specific importance, which offers numerous possibilities for interactions with melatonin. It is an aim of this review to stimulate research on melatonin signaling in peripheral tissues. This should not be restricted to primary signal molecules but rather include various secondarily connected pathways and discriminate between direct effects of the pineal indoleamine at the target organ and others mediated by modulation of oscillators.
Journal of Pineal Research 03/2012; 52(2):139-66. · 5.79 Impact Factor
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ABSTRACT: Circadian rhythms (approximately 24h) are widely characterized at molecular level and their generation is acknowledged to originate from oscillations in expression of several clock genes and from regulation of their protein products. While general entrainment of organisms to environmental light-dark cycles is mainly achieved through the master clock of the suprachiasmatic nucleus in mammals, this molecular clockwork is functional in several organs and tissues. Some studies have suggested that disruption of the circadian system (chronodisruption (CD)) may be causal for manifestations of the metabolic syndrome. This review summarizes (1) how molecular clocks coordinate metabolism and their specific role in the adipocyte; (2) the genetic aspects of and scientific evidence for obesity as a chronobiological illness; and (3) CD and its causes and pathological consequences. Finally, ideas about use of chronobiology for the treatment of obesity are discussed.
Endocrinología y Nutrición 11/2011; 59(1):50-61.
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ABSTRACT: Menopausal women exhibit a loss of circadian coordination, a process that runs parallel with a redistribution of adipose tissue. However, the specific genetic mechanisms underlying these alterations have not been studied. Thus, the aim of the present study was to determine whether the development of menopause induces an alteration of the genes that control biological rhythms in human subcutaneous (SAT) and visceral (VAT) adipose tissue, and whether changes in clock gene expression are involved in the increased risk of developing metabolic syndrome (MetS), which is frequently associated with menopause. To this end, VAT and SAT biopsies were taken in pre- (n = 7) and postmenopausal (n = 7) women at similar hours in the morning. RNA was extracted, and a microarray analysis was made. Data were confirmed by quantitative real-time polymerase chain reaction. Western blot and immunohistochemical analysis were also performed. When clock gene expression was compared between both groups of women, data in SAT showed that expression of the core clock gene period3 was significantly higher in postmenopausal women, while casein kinase-1δ, E1A-binding protein and cAMP-responsive element were preferentially expressed in the premenopausal group. In VAT, period2 (PER2) and v-myc myelocytomatosis viral oncogene expressions were significantly higher in the postmenopausal group. Western blot analysis indicated that PER2 and PER3 protein expression was also increased in postmenopausal women. In addition, several genes, including PER2, were differentially expressed depending on whether or not the patient met the MetS criteria. We conclude that menopause transition induces several changes in the genotype of the adipose tissue chronobiological machinery related to an increased risk of developing MetS.
Age 09/2011; · 6.28 Impact Factor
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ABSTRACT: Daily exposure to environmental light is the most important zeitgeber in humans, and all studied characteristics of light pattern (timing, intensity, rate of change, duration, and spectrum) influence the circadian system. However, and due to lack of current studies on environmental light exposure and its influence on the circadian system, the aim of this work is to determine the characteristics of a naturalistic regimen of light exposure and its relationship with the functioning of the human circadian system. Eighty-eight undergraduate students (18-23 yrs) were recruited in Murcia, Spain (latitude 38°01'N) to record wrist temperature (WT), light exposure, and sleep for 1 wk under free-living conditions. Light-exposure timing, rate of change, regularity, intensity, and contrast were calculated, and their effects on the sleep pattern and WT rhythm were then analyzed. In general, higher values for interdaily stability, relative amplitude, mean morning light, and light quality index (LQI) correlated with higher interdaily stability and relative amplitude, and phase advance in sleep plus greater stability in WT and phase advance of the WT circadian rhythm. On the other hand, a higher fragmentation of the light-exposure rhythm was associated with more fragmented sleep. Naturalistic studies using 24-h ambulatory light monitoring provide essential information about the main circadian system input, necessary for maintaining healthy circadian tuning. Correcting light-exposure patterns accordingly may help prevent or even reverse health problems associated with circadian disruption.
Chronobiology International 08/2011; 28(7):617-29. · 4.03 Impact Factor
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ABSTRACT: The authors developed a method useful for home measurement of temperature, activity, and sleep rhythms in infants under normal-living conditions during their first 6 mos of life. In addition, parametric and nonparametric tests for assessing circadian system maturation in these infants were compared. Anthropometric parameters plus ankle skin temperature and activity were evaluated in 10 infants by means of two data loggers, Termochron iButton (DS1291H, Maxim Integrated Products, Sunnyvale, CA) for temperature and HOBO Pendant G (Hobo Pendant G Acceleration, UA-004-64, Onset Computer Corporation, Bourne, MA) for motor activity, located in special baby socks specifically designed for the study. Skin temperature and motor activity were recorded over 3 consecutive days at 15 days, 1, 3, and 6 mos of age. Circadian rhythms of skin temperature and motor activity appeared at 3 mos in most babies. Mean skin temperature decreased significantly by 3 mos of life relative to previous measurements (p = .0001), whereas mean activity continued to increase during the first 6 mos. For most of the parameters analyzed, statistically significant changes occurred at 3-6 mos relative to 0.5-1 mo of age. Major differences were found using nonparametric tests. Intradaily variability in motor activity decreased significantly at 6 mos of age relative to previous measurements, and followed a similar trend for temperature; interdaily stability increased significantly at 6 mos of age relative to previous measurements for both variables; relative amplitude increased significantly at 6 mos for temperature and at 3 mos for activity, both with respect to previous measurements. A high degree of correlation was found between chronobiological parametric and nonparametric tests for mean and mesor and also for relative amplitude versus the cosinor-derived amplitude. However, the correlation between parametric and nonparametric equivalent indices (acrophase and midpoint of M5, interdaily stability and Rayleigh test, or intradaily variability and P(1)/P(ultradian)) despite being significant, was lower for both temperature and activity. The circadian function index (CFI index), based on the integrated variable temperature-activity, increased gradually with age and was statistically significant at 6 mos of age. At 6 mos, 90% of the infants' rest period coincided with the standard sleep period of their parents, defined from 23:00 to 07:00 h (dichotomic index I < O; when I < O = 100%, there is a complete coincidence between infant nocturnal rest period and the standard rest period), whereas at 15 days of life the coincidence was only 75%. The combination of thermometry and actimetry using data loggers placed in infants' socks is a reliable method for assessing both variables and also sleep rhythms in infants under ambulatory conditions, with minimal disturbance. Using this methodological approach, circadian rhythms of skin temperature and motor activity appeared by 3 mos in most babies. Nonparametric tests provided more reliable information than cosinor analysis for circadian rhythm assessment in infants.
Chronobiology International 05/2011; 28(4):330-7. · 4.03 Impact Factor
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ABSTRACT: Although it is well established that human adipose tissue (AT) shows circadian rhythmicity, published studies have been discussed as if tissues or systems showed only one or few circadian rhythms at a time.AIM: To provide an overall view of the internal temporal order of circadian rhythms in human AT including genes implicated in metabolic processes such as energy intake and expenditure, insulin resistance, adipocyte differentiation, dyslipidemia, and body fat distribution. METHODS: Visceral and subcutaneous abdominal AT biopsies (n=6) were obtained from morbid obese women (BMI≥40 kg/m(2)). To investigate rhythmic expression pattern, AT explants were cultured during 24-h and gene expression was analyzed at the following times: 0800, 1400, 2000, 0200 h using quantitative real-time PCR. Clock genes, glucocorticoid metabolism-related genes, Leptin, Adiponectin and their receptors were studied. RESULTS: Significant differences were found both in achrophases and relative-amplitude among genes (P<0.05). Amplitude of most genes rhythms was high (>30%). When interpreting the phase map of gene expression in both depots, data indicated that circadian rhythmicity of the genes studied followed a predictable physiological pattern, particularly for subcutaneous AT. Interesting are the relationships between adiponectin, leptin and glucocorticoid metabolism-related genes circadian profiles. Their metabolic significance is discussed. Visceral AT behaved in a different way than subcutaneous for most of the genes studied. For every gene , protein mRNA levels fluctuated during the day in synchrony with its receptors. CONCLUSION: We have provided an overall view of the internal temporal order of circadian rhythms in human adipose tissue. © 2010 Wiley-Liss, Inc.
Journal of Cellular Physiology 12/2010; · 3.87 Impact Factor
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ABSTRACT: This study focuses on the effects of retinal degeneration on the circadian patterns of P23H rats, as well as on the effect of exogenous melatonin administration. To this end, the body temperature of P23H and Sprague-Dawley rats was continuously monitored and their retinas examined at different stages of degeneration, by means of histological labeling and electroretinogram recordings. Melatonin (2 mg/kg BW/day) was supplied ad libitum throughout the experiment to a subset of animals. The body temperature recordings from wild-type and mutant animals showed no differences in the periodogram and the pattern of the mean waveform. However, a progressive decrease in the relative amplitude of the rhythm (RA), a decline in the coupling strength of the rhythm to environmental zeitgebers (interdaily stability, IS) and increased rhythm fragmentation (intradaily variability, IV) were observed in P23H rats, when compared to wild-type animals. The P23H animals showed a progressive decrease in light-induced retinal responses until reaching 18 months of age. By this age, all photoreceptors had already disappeared, and no responses were found in the EGRs. Exogenous administration of melatonin improved the visual response of P23H rats. In fact, the maximum b-wave recorded at 14 months of age was significantly higher in melatonin-treated P23H rats than in the control animals. Furthermore, the maximum b-wave recorded for P23H rats at the age of 14 months significantly correlated with RA, IS, and IV. This leads us to conclude that vision loss in P23H rats is correlated with a progressive fragmentation of their circadian patterns. Both effects are partially reversed by melatonin administration.
Journal of Pineal Research 11/2010; 50(2):183-91. · 5.79 Impact Factor
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ABSTRACT: Daily rhythms in different biochemical and hematological variables have been widely described in either diurnal or nocturnal species, but so far no studies in the rhythms of these variables have been conducted in a dual-phasing species such as the degus. The Octodon degus is a rodent that has the ability to switch from diurnal to nocturnal activity under laboratory conditions in response to wheel-running availability. This species may help us discover whether a complete temporal order inversion occurs parallel to the inversion that has been observed in this rodent's activity pattern. The aim of the present study is to determine the phase relationships among 26 variables, including behavioral, physiological, biochemical, and hematological variables, during the day and at night, in diurnal and nocturnal degus chronotypes induced under controlled laboratory conditions through the availability of wheel running. A total of 39 male degus were individually housed under a 12:12 light-dark (LD) cycle, with free wheel-running access. Wheel-running activity (WRA) and body temperature (Tb) rhythms were recorded throughout the experiment. Melatonin, hematological, and biochemical variables were determined by means of blood samples obtained every 6 h (ZT1, ZT7, ZT13, and ZT19). In spite of great differences in WRA and Tb rhythms between nocturnal and diurnal degus, no such differences were observed in the temporal patterns of most of the biological variables analyzed for the two chronotypes. Variation was only found in plasma urea level and lymphocyte number. A slight delay in the phase of the melatonin rhythm was also observed. This study shows the internal temporal order of a dual-phasing mammal does not show a complete inversion in accordance with its activity and body temperature pattern; it would appear that the switching mechanism involved in the degu's nocturnalism is located downstream from the pacemaker.
Chronobiology International 09/2010; 27(8):1564-79. · 4.03 Impact Factor
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ABSTRACT: Octodon degus is a primarily diurnal rodent that presents great variation in its circadian chronotypes due to the interaction between two phase angles of entrainment, diurnal and nocturnal, and the graded masking effects of environmental light and temperature. The aim of this study was to test whether the circadian system of this diurnal rodent can be internally dissociated by imposing cycles shorter and longer than 24 h, and to determine the influence of degus chronotypes and wheel-running availability on such dissociation. To this end, wheel-running activity and body temperature rhythms were studied in degus subjected to symmetrical light-dark (LD) cycles of T28h and T21h. The results show that both T-cycles dissociate the degus circadian system in two different components: one light-dependent component (LDC) that is influenced by the presence of light, and a second non-light-dependent component (NLDC) that free-runs with a period different from the external lighting cycle. The LDC was more evident in the nocturnal than diurnal chronotype, and also when wheel running was available. Our results show that, in addition to rats and mice, degus must be added to the list of species that show an internal dissociation in their circadian rhythms when exposed to forced desynchronization protocols. The existence of a multioscillatory circadian system having two groups of oscillators with low coupling strength may explain the flexibility of degus chronotypes.
Chronobiology International 09/2010; 27(8):1580-95. · 4.03 Impact Factor
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ABSTRACT: There are two main processes involved in the expression of circadian rhythmicity: entrainment and masking. Whereas the first operates via the central pacemaker to anticipate predictable environmental conditions, masking (mainly induced by light) functions as a direct modulator of the circadian output signal induced by nonpredictable events. The Chilean rodent Octodon degus presents both diurnal and nocturnal chronotypes when given free access to an exercise wheel. Two steady-entrainment phases and graded masking by light seem to generate the wide variability of chronotypes in this species. The aim of this study was to characterize the differential masking by light according to the individual chronotypes, their stability over time, and the influence of wheel running availability and ambient temperature upon the degus' nocturnality. To this end, diurnal and nocturnal degus were subjected to ultradian cycles (1:1-h light-dark [LD]), with and without wheel running availability, and under both normal and high diurnal ambient temperature cycles. The present results show that diurnal and nocturnal degus present a stable masking by light, each according to its respective chronotype. Thus, whereas diurnal animals increased their activity with light, in nocturnal degus light induced a sharp drop in wheel running activity. These two types of masking responses appeared not only when the animals were synchronized to the 12:12-h LD cycle, but also under ultradian cycles. Different masking effects persisted when wheel running was made unavailable and when the animals shifted their circadian activity patterns in response to ultradian cycles or to diurnal exposure to high temperatures. In conclusion, our results show that the positive and negative masking effects of light on diurnal and nocturnal degus, respectively, seem to occur independently of relative phase control by the central pacemaker or the negative masking induced by high environmental temperatures.
Chronobiology International 08/2010; 27(7):1365-79. · 4.03 Impact Factor
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ABSTRACT: The present review starts from the classical physiological and nutritional studies related with food intake control, digestion, transport and absorption of nutrients. It continues with studies related with the metabolism of adipose tissue, and finish with modern experiments in genetics and molecular biology - all from a fresh, chronobiological point of view. Obesity will be explained as a fault in the circadian system, as pathology associated with "chronodisruption". The main gaps in chronobiological research related to obesity will be also identified and chronobiological-based therapies will be proposed in order to allow the resetting of the circadian rhythm among obese subjects.
Advanced drug delivery reviews 07/2010; 62(9-10):967-78. · 11.96 Impact Factor
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ABSTRACT: Body temperature regulation within a physiological range is a critical factor for guaranteeing the survival of living organisms. The avoidance of high ambient temperatures is a behavioral mechanism used by homeothermic animals living in extreme environmental conditions. As the circadian system is involved in these thermoregulatory responses, precise phase shifts and even complete temporal niche inversion have been reported. Octodon degus, a mainly diurnal rodent from Chile, has the ability to switch its phase preference for locomotor activity to coincide with the availability of a running wheel. The aims of this work are twofold: to determine whether ambient temperature cycles, with high values during the day and low values at night (HLT(a)), can induce nocturnal chronotypes in degus previously characterized as diurnal; and to learn whether HLT(a) cycles are able to act as a zeitgeber in this dual-phase species. To this end, degus were subjected to 24 h HLT(a) cycles under both 12:12 LD and DD conditions. Two experimental groups were used, one with previous wheel running experience and another naïve group, to study the influence of the thermal cycles and previous wheel running experience on the degus' dual-phasing behavior. Temperature cycles (31.3 +/- 1.5 degrees C during the day and 24.2 +/- 1.6 degrees C at night) induced a 100% nocturnalism in previously diurnal individuals. Indeed, both entrainment with nocturnal phase angle to LD and nocturnal rhythmicity induced by masking were observed. Moreover, HLT(a) cycles acted by masking, confining wheel-running activity to the cooler phase under DD conditions, with the naïve group being more sensitive than the experienced one.
Chronobiology International 05/2010; 27(3):517-34. · 4.03 Impact Factor
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ABSTRACT: Gender differences in spatial navigation have been widely reported in nocturnal rodent species. Here, for the first time we report gender differences in spatial learning and memory of Octodon degus, a long-lived diurnal hystricomorph rodent. In the present study, 16 months old male and female O. degus were tested in the 18-holes Barnes circular maze. The acquisition session consisted of four daily 4 min trials, during 10 days. Seven days later, the retention test was performed. To avoid the effect of hormonal fluctuation on spatial navigation, both the acquisition and the retention tests, were performed in 21-day regular cycling females in a period that corresponds to the diestrus phase of the estrus cycle. At the beginning of the acquisition, female degus were significantly slower than males to find the escape hole, but the situation reversed afterwards. Moreover, during the course of acquisition, females made significantly less reference memory errors, working memory errors as well as omission errors, than males. In both sexes, motivation and learning ceiling effects were reached at days 5-6 of the training. During the acquisition, females used more frequently a spatial strategy, while males preferably applied either serial, random or opposite strategies. The observed cognitive differences between male and female O. degus existed only during the acquisition period but not during the retention, indicating that acquisition and consolidation are differently influenced by gender.
Behavioural brain research 04/2010; 212(2):159-67. · 3.22 Impact Factor
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ABSTRACT: Circadian rhythms are controlled by interlocked autoregulatory feedback loops consisting of interactions of a group of circadian clock genes and their proteins. The Period family is a group of genes that are essential components of the molecular clock. In the present study, we cloned a period gene (per1) of the European sea bass, a marine teleost of chronobiological interest. The cloned sequence encoded a protein consisting of 1436 amino acids that homology and phylogenic analyses showed to be related with fish PER1 proteins possessing very high identity with Oryzias latipes (Medaka) per1. Polymerase chain reaction screening of per1 expression showed that this gene is expressed in all the tissues analyzed (brain, heart, liver, gill, muscle, digestive tract, adipose tissue, spleen, and retina). In addition, a daily expression rhythm, with an acrophase (peak time) approximately ZT0 (lights-on), was found in the two tissue types investigated: neural (brain) and peripheral (liver and heart). In conclusion, identification and characterization of the gene encoding sea bass per1 provide valuable information for understanding the circadian mechanism at the molecular level in this species, although further research is needed to clarify the exact role that per1 plays in the circadian oscillator and the dual behavior of European sea bass.
Chronobiology International 01/2010; 27(1):19-33. · 4.03 Impact Factor
