Relationship between locomotor activity rhythm and corticosterone levels during HCC development, progression, and treatment in a mouse model.

Cancer-related fatigue (CRF) and stress are common symptoms in cancer patients and represent early side effects of cancer treatment which affect the life quality of the patients. CRF may partly depend on disruption of the circadian rhythm. Locomotor activity and corticosterone rhythms are two important circadian outputs which can be used to analyze possible effects on the circadian function during cancer development and treatment. The present study analyzes the relationship between locomotor activity rhythm, corticosterone levels, hepatocellular carcinoma (HCC) development, and radiotherapy treatment in a mouse model. HCC was induced in mice by single injection of diethylnitrosamine (DEN) and chronic treatment of phenobarbital in drinking water. Another group received chronic phenobarbital treatment only. Tumor bearing animals were divided randomly into four groups irradiated at four different Zeitgeber time points. Spontaneous locomotor activity was recorded continuously; serum corticosterone levels and p-ERK immunoreaction in the suprachiasmatic nucleus (SCN) were investigated. Phenobarbital treated mice showed damped corticosterone levels and a less stable 24 hours activity rhythm as well as an increase in activity during the light phase, reminiscent of sleep disruption. The tumor mice showed an increase in corticosterone level during the inactive phase and decreased activity during the dark phase, reminiscent of CRF. After irradiation, corticosterone levels were further increased and locomotor activity rhythms were disrupted. Lowest corticosterone levels were observed after irradiation during the early light phase; thus, this time might be the best to apply radiotherapy in order to minimize side effects.

Disruption in daily eating-fasting and activity-rest cycles in Indian adolescents attending school.

A lifestyle with erratic eating patterns and habits predisposes youngsters to obesity. Through a two-phase feasibility study among Indian students living in the Delhi area, we longitudinally examined the following: (1) the daily eating-fasting cycles of students (N = 34) in school and college using smartphones as they transition from high school (aged 13-15 years; nIX = 13) to higher secondary school (HSSS; 16-18 years; nXII = 9) to their first year (FY) of college (18-19 years; nFC = 12); and (2) daily activity-rest cycles and light-dark exposure of 31 higher secondary school students (HSSS) using actigraphy. In phase 1, students' food data were analyzed for temporal details of eating events and observable differences in diet composition, such as an energy-dense diet (fast food (FF)), as confounding factors of circadian health. Overall, the mean eating duration in high school, higher secondary and FY college students ranged from 14.1 to 16.2h. HSSS exhibited the shortest night fasting. Although FY college students exhibited the highest fast food percentage (FF%), a positive correlation between body mass index (BMI) and FF% was observed only among HSSS. Furthermore, the body weight of HSSS was significantly higher, indicating that FF, untimely eating and reduced night fasting were important obesity-associated factors in adolescents. Reduced night fasting duration was also related to shorter sleep in HSSS. Therefore, food data were supplemented with wrist actigraphy, i.e., activity-rest data, in HSSS. Actigraphy externally validated the increased obesogenic consequences of deregulated eating rhythms in HSSS. CamNtech motion watches were used to assess the relationship between disturbed activity cycles of HSSS and other circadian clock-related rhythms, such as sleep. Less than 50% of Indian HSSS slept 6 hours or more per night. Seven of 31 students remained awake throughout the night, during which they had more than 20% of their daily light exposure. Three nonparametric circadian rhythm analysis (NPCRA) variables revealed circadian disruption of activity in HSSS. The present study suggests that inappropriate timing and quality of food and sleep disturbances are important determinants of circadian disruptions in adolescents attending school.

Estimating Representative Group Intrinsic Circadian Period from Illuminance-Response Curve Data.

The human circadian pacemaker entrains to the 24-h day, but interindividual differences in properties of the pacemaker, such as intrinsic period, affect chronotype and mediate responses to challenges to the circadian system, such as shift work and jet lag, and the efficacy of therapeutic interventions such as light therapy. Robust characterization of circadian properties requires desynchronization of the circadian system from the rest-activity cycle, and these forced desynchrony protocols are very time and resource intensive. However, circadian protocols designed to derive the relationship between light intensity and phase shift, which is inherently affected by intrinsic period, may be applied more broadly. To exploit this relationship, we applied a mathematical model of the human circadian pacemaker with a Markov-Chain Monte Carlo parameter estimation algorithm to estimate the representative group intrinsic period for a group of participants using their collective illuminance-response curve data. We first validated this methodology using simulated illuminance-response curve data in which the intrinsic period was known. Over a physiological range of intrinsic periods, this method accurately estimated the representative intrinsic period of the group. We also applied the method to previously published experimental data describing the illuminance-response curve for a group of healthy adult participants. We estimated the study participants' representative group intrinsic period to be 24.26 and 24.27 h using uniform and normal priors, respectively, consistent with estimates of the average intrinsic period of healthy adults determined using forced desynchrony protocols. Our results establish an approach to estimate a population's representative intrinsic period from illuminance-response curve data, thereby facilitating the characterization of intrinsic period across a broader range of participant populations than could be studied using forced desynchrony protocols. Future applications of this approach may improve the understanding of demographic differences in the intrinsic circadian period.

Effects of a dawn-dusk simulation on circadian rest-activity cycles, sleep, mood and well-being in dementia patients.

Light is the most powerful "zeitgeber" signal to synchronize circadian sleep-wake cycles. In dementia, these rhythms are often fragmented - probably due to loss of neuronal function of the suprachiasmatic nuclei (the biological "master clock" in the brain) and/or weakness of external zeitgebers. We investigated the effects of a prototype dawn-dusk simulator (DDS) on circadian rest-activity cycles, sleep, mood and well-being in a balanced crossover design during fall and winter in 20 institutionalized patients with dementia (86 ±â€¯6 y, 17 f). All participants had one baseline week followed by exposure to individually timed DDS over their beds for 7-8 weeks. They spent 8 weeks without DDS as a control. Mood, self-reliant daily activity, social behavior, agitation, and quality of life were assessed by standardized questionnaires and visual analogue scales, regularly rated by trained caregivers. Circadian and sleep characteristics of their rest-activity cycles were analyzed by actimetry over 17 weeks. DDS exposure led to significantly better mood in the morning hours after waking. The effects were most pronounced in the second 4 weeks with DDS, indicating that positive effects emerged gradually. Differences in circadian rest-activity cycles and sleep were mainly age-dependent. We found statistically significant correlations between measures of higher quality of life and better mood, greater alertness and circadian rhythm stability. We conclude that continuous, long-term application of dawn-dusk simulation at the sleep-wake transitions appears to increase external zeitgeber strength in institutionalized patients with dementia. The DDS may provide an effective, non-invasive tool to improve mood and ameliorate patients' quality of life.

Effect of bright light therapy on delayed sleep/wake cycle and reaction time of athletes participating in the Rio 2016 Olympic Games.

This study investigated the effect of using an artificial bright light on the entrainment of the sleep/wake cycle as well as the reaction times of athletes before the Rio 2016 Olympic Games. A total of 22 athletes from the Brazilian Olympic Swimming Team were evaluated, with the aim of preparing them to compete at a time when they would normally be about to go to bed for the night. During the 8-day acclimatization period, their sleep/wake cycles were assessed by actigraphy, with all the athletes being treated with artificial light therapy for between 30 and 45 min (starting at day 3). In addition, other recommendations to improve sleep hygiene were made to the athletes. In order to assess reaction times, the Psychomotor Vigilance Test was performed before (day 1) and after (day 8) the bright light therapy. As a result of the intervention, the athletes slept later on the third (p = 0.01), seventh (p = 0.01) and eighth (p = 0.01) days after starting bright light therapy. Regarding reaction times, when tested in the morning the athletes showed improved average (p = 0.01) and minimum reaction time (p = 0.03) when comparing day 8 to day 1. When tested in the evening, they showed improved average (p = 0.04), minimum (p = 0.03) and maximum reaction time (p = 0.02) when comparing day 8 to day 1. Light therapy treatment delayed the sleep/wake cycles and improved reaction times of members of the swimming team. The use of bright light therapy was shown to be effective in modulating the sleep/wake cycles of athletes who had to perform in competitions that took place late at night.

Temporal expression of clock genes in central and peripheral tissues of spotted munia under varying light conditions: Evidence for circadian regulation of daily physiology in a non-photoperiodic circannual songbird species.

We investigated if the duration and/or frequency of the light period affect 24-h rhythm of circadian clock genes in central and peripheral tissues of a non-photoperiodic songbird, the spotted munia (Lonchura punctulata), in which a circannual rhythm regulates the reproductive cycle. We monitored activity-rest pattern and measured 24-h mRNA oscillation of core clock (Bmal1, Clock, Per2, Cry1 and Cry2) and clock-controlled (E4bp4, Rorα and Rev-erbα) genes in the hypothalamus, retina, liver and gut of spotted munia subjected to an aberrant light-dark (LD) cycle (3.5L:3.5D; T7, T = period length of LD cycle) and continuous light (LL, 24L:0D), with controls on 24-h LD cycle (T24, 12L:12D). Munia exhibited rhythmic activity-rest pattern with period matched to T7 or T24 under an LD cycle and were arrhythmic with a scattered activity pattern and higher activity duration under LL. At the transcriptional level, both clock and clock-controlled genes showed a significant 24-h rhythm in all four tissues (except Clock in the liver) under 12L:12D, suggesting a conserved tissue-level circadian time generation in spotted munia. An exposure to 3.5L:3.5D or LL induced arrhythmicity in transcriptional oscillation of all eight genes in the hypothalamus (except Rev-erbα) and liver (except Bmal1 and Rev-erbα under T7 and Cry1 under LL). In the retina, however, all genes showed arrhythmic 24-h mRNA expression under LL, but not under T7 (except in E4bp4 and Rorα). Interestingly, unlike in the liver, Bmal1, Per2, Cry1, Rorα and Rev-erbα mRNA expressions were rhythmic in the gut under both T7 (except Rorα) and LL conditions. These results showed variable relationship of internal circadian clocks with the external light environment and suggested a weak coupling of circadian clocks between the central (hypothalamus and retina) and peripheral (liver and gut) tissues. We suggest tissue-level circadian clock regulation of daily physiology and behavior in the spotted munia.

Feeding during the rest phase promotes circadian conflict in nuclei that control energy homeostasis and sleep-wake cycle in rats.

Food intake during the rest phase promotes circadian desynchrony, which has been associated with metabolic diseases. However, the link between circadian rhythm and metabolic alterations is not well understood. To investigate this issue, we explored the circadian rhythm of c-Fos immunoreactivity (IR) in rats fed during the day, during the night or with free access to food for 3 weeks. The analysis was focused on the hypothalamic nuclei, which are interconnected and involved in the control of energy homeostasis and/or arousal: lateral hypothalamus (LH), perifornical area, arcuate, ventrolateral pre-optic (VLPO) and tuberomammillary nuclei. The results show that food intake during the rest phase flattened the circadian c-Fos expression in the LH and perifornical area, and induced a phase shift in the VLPO area. In addition, c-Fos expression was analyzed in the orexin and melanin-concentrating hormone (MCH) neurons of the LH, which are involved in the control of food intake and arousal, and in α-melanin-stimulating hormone and neuropeptide Y (NPY) cells in the arcuate nucleus, all of which are involved in feeding-fasting cycles, energy homeostasis and sending projections to the LH. The results indicate that feeding during the rest phase decreased orexin neuron activation in the light in comparison with the other groups. Feeding during this phase also flattened the activity rhythm of MCH and α-melanin-stimulating hormone neurons and increased NPY IR when the light was turned on. This evidence indicates that mealtime differentially affected the hypothalamic nuclei under investigation leading to a circadian conflict that might account for metabolic impairment.

Optogenetic activation of melanin-concentrating hormone neurons increases non-rapid eye movement and rapid eye movement sleep during the night in rats.

Neurons containing melanin-concentrating hormone (MCH) are located in the hypothalamus. In mice, optogenetic activation of the MCH neurons induces both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep at night, the normal wake-active period for nocturnal rodents [R. R. Konadhode et al. (2013) J. Neurosci., 33, 10257-10263]. Here we selectively activate these neurons in rats to test the validity of the sleep network hypothesis in another species. Channelrhodopsin-2 (ChR2) driven by the MCH promoter was selectively expressed by MCH neurons after injection of rAAV-MCHp-ChR2-EYFP into the hypothalamus of Long-Evans rats. An in vitro study confirmed that the optogenetic activation of MCH neurons faithfully triggered action potentials. In the second study, in Long-Evans rats, rAAV-MCH-ChR2, or the control vector, rAAV-MCH-EYFP, were delivered into the hypothalamus. Three weeks later, baseline sleep was recorded for 48 h without optogenetic stimulation (0 Hz). Subsequently, at the start of the lights-off cycle, the MCH neurons were stimulated at 5, 10, or 30 Hz (1 mW at tip; 1 min on - 4 min off) for 24 h. Sleep was recorded during the 24-h stimulation period. Optogenetic activation of MCH neurons increased both REM and NREM sleep at night, whereas during the day cycle, only REM sleep was increased. Delta power, an indicator of sleep intensity, was also increased. In control rats without ChR2, optogenetic stimulation did not increase sleep or delta power. These results lend further support to the view that sleep-active MCH neurons contribute to drive sleep in mammals.

Feeding during the resting phase causes profound changes in physiology and desynchronization between liver and muscle rhythms of rats.

Shiftworkers run an increased risk of developing metabolic disorders, presumably as a result of disturbed circadian physiology. Eating at a time-of-day that is normally dedicated to resting and fasting, may contribute to this association. The hypothalamus is the key brain area that integrates different inputs, including environmental time information from the central biological clock in the suprachiasmatic nuclei, with peripheral information on energy status to maintain energy homeostasis. The orexin system within the lateral hypothalamus is an important output of the suprachiasmatic nuclei involved in the control of sleep/wake behavior and glucose homeostasis, among other functions. In this study, we tested the hypothesis that feeding during the rest period disturbs the orexin system as a possible underlying contributor to metabolic health problems. Male Wistar rats were exposed to an 8-week protocol in which food was available ad libitum for 24-h, for 12-h during the light phase (i.e., unnatural feeding time) or for 12-h during the dark phase (i.e., restricted feeding, but at the natural time-of-day). Animals forced to eat at an unnatural time, i.e., during the light period, showed no changes in orexin and orexin-receptor gene expression in the hypothalamus, but the rhythmic expression of clock genes in the lateral hypothalamus was absent in these animals. Light fed animals did show adverse changes in whole-body physiology and internal desynchronization of muscle and liver clock and metabolic gene expression. Eating at the 'wrong' time-of-day thus causes internal desynchronization at different levels, which in the long run may disrupt body physiology.

Effectiveness of internet-supported cognitive behavioral and chronobiological interventions and effect moderation by insomnia subtype: study protocol of a randomized controlled trial.

BACKGROUND: DSM-V criteria for insomnia disorder are met by 6 to 10% of the adult population. Insomnia has severe consequences for health and society. One of the most common treatments provided by primary caregivers is pharmacological treatment, which is far from optimal and has not been recommended since a 2005 consensus report of the National Institutes of Health. The recommended treatment is Cognitive Behavioral Therapy for Insomnia. Effectiveness, however, is still limited. Only a few studies have evaluated the effectiveness of chronobiological treatments, including the timed application of bright light, physical activity and body warming. Another opportunity for optimization of treatment is based on the idea that the people suffering from insomnia most likely represent a heterogeneous mix of subtypes, with different underlying causes and expected treatment responses. The present study aims to evaluate the possibility for optimizing insomnia treatment along the principles of personalized and stratified medicine. It evaluates the following: 1. The relative effectiveness of internet-supported cognitive behavioral therapy, bright light, physical activity and body warming; 2. Whether the effectiveness of internet-supported cognitive behavioral therapy for insomnia can be augmented by simultaneous or prior application of bright light, physical activity and body warming; and 3. Whether the effectiveness of the interventions and their combination are moderated by the insomnia subtype. METHODS/DESIGN: In a repeated measures, placebo-controlled, randomized clinical trial that included 160 people diagnosed with insomnia disorder, we are evaluating the relative effectiveness of 4 intervention weeks. Primary outcome is subjective sleep efficiency, quantified using a sleep diary. Secondary outcomes include other complaints of sleep and daytime functioning, health-related cost estimates and actigraphic objective sleep estimates. Compliance will be monitored both subjectively and objectively using activity, light and temperature sensors. Insomnia subtypes will be assessed using questionnaires. Mixed effect models will be used to evaluate intervention effects and moderation by insomnia subtype ratings. DISCUSSION: The current study addresses multiple opportunities to optimize and personalize treatment of insomnia disorder. TRIAL REGISTRATION: Netherlands National Trial Register NTR4010, 4 June 2013.

Rats with minimal hepatic encephalopathy show reduced cGMP-dependent protein kinase activity in hypothalamus correlating with circadian rhythms alterations.

Patients with liver cirrhosis show disturbances in sleep and in its circadian rhythms which are an early sign of minimal hepatic encephalopathy (MHE). The mechanisms of these disturbances are poorly understood. Rats with porta-caval shunt (PCS), a model of MHE, show sleep disturbances reproducing those of cirrhotic patients. The aims of this work were to characterize the alterations in circadian rhythms in PCS rats and analyze the underlying mechanisms. To reach these aims, we analyzed in control and PCS rats: (a) daily rhythms of spontaneous and rewarding activity and of temperature, (b) timing of the onset of activity following turning-off the light, (c) synchronization to light after a phase advance and (d) the molecular mechanisms contributing to these alterations in circadian rhythms. PCS rats show altered circadian rhythms of spontaneous and rewarding activities (wheel running). PCS rats show more rest bouts during the active phase, more errors in the onset of motor activity and need less time to re-synchronize after a phase advance than control rats. Circadian rhythm of body temperature is also slightly altered in PCS rats. The internal period length (tau) of circadian rhythm of motor activity is longer in PCS rats. We analyzed some mechanisms by which hypothalamus modulate circadian rhythms. PCS rats show increased content of cGMP in hypothalamus while the activity of cGMP-dependent protein kinase was reduced by 41% compared to control rats. Altered cGMP-PKG pathway in hypothalamus would contribute to altered circadian rhythms and synchronization to light.

The psychiatry of light.

Bright light therapy and the broader realm of chronotherapy remain underappreciated and underutilized, despite their empirical support. Efficacy extends beyond seasonal affective disorder and includes nonseasonal depression and sleep disorders, with emerging evidence for a role in treating attention-deficit/hyperactivity disorder, delirium, and dementia. A practical overview is offered, including key aspects of underlying biology, indications for treatment, parameters of treatment, adverse effects, and transformation of our relationship to light and darkness in contemporary life.

Nasal cycle dominance and hallucinations in an adult schizophrenic female.

Nasal dominance, at the onset of hallucinations, was studied as a marker of both the lateralized ultradian rhythm of the autonomic nervous system and the tightly coupled ultradian rhythm of alternating cerebral hemispheric dominance in a single case study of a schizophrenic female. Over 1086 days, 145 hallucination episodes occurred with left nostril dominance significantly greater than the right nostril dominant phase of the nasal cycle. A right nostril breathing exercise, that primarily stimulates the left hemisphere, reduces symptoms more quickly for hallucinations.

Effects of sleep hygiene and artificial bright light interventions on recovery from simulated international air travel.

PURPOSE: Despite the reported detrimental effects of international air travel on physical performance, a paucity of interventions have been scientifically tested and confirmed to benefit travelling athletes. Consequently, the aim of the present study was to examine the effects of sleep hygiene and artificial bright light interventions on physical performance following simulated international travel. METHODS: In a randomized crossover design, 13 physically active males completed 24 h of simulated international travel with (INT) and without (CON) the interventions. The mild hypoxia and cramped conditions typically encountered during commercial air travel were simulated in a normobaric, hypoxic room. Physical performance, subjective jet-lag symptoms and mood states were assessed in the morning and evening on the day prior to and for two days post-travel. Sleep quantity and quality were monitored throughout each trial. RESULTS: Sleep duration was significantly reduced during travel in both trials (P < 0.01), though total sleep duration during and following travel was almost significantly greater (P = 0.06) in INT (17.0 (16.2-17.8) h) compared to CON (15.7 (14.9-16.5) h). Maximal-sprint and countermovement jump (P < 0.05), but not Yo-Yo Intermittent Recovery level 1 test (P > 0.05) performance, were significantly reduced the evening of day 1 and 2 post-travel, with no differences between trials (P > 0.05). Furthermore, vigour was significantly greater (P = 0.04) the morning of day 2 in INT [5.3 (3.9-6.7)] compared to CON [2.8 (1.4-4.2)], and subjective jet-lag symptoms and mood states were significantly worse on day 2 in CON only (P < 0.05). CONCLUSIONS: Whilst reducing travel-induced sleep disruption may attenuate travel fatigue, no improvements in the recovery of physical performance were apparent.

Impaired leukocyte trafficking and skin inflammatory responses in hamsters lacking a functional circadian system.

The immune system is under strong circadian control, and circadian desynchrony is a risk factor for metabolic disorders, inflammatory responses and cancer. Signaling pathways that maintain circadian rhythms (CRs) in immune function in vivo, and the mechanisms by which circadian desynchrony impairs immune function, remain to be fully identified. These experiments tested the hypothesis that the hypothalamic circadian pacemaker in the suprachiasmatic nucleus (SCN) drives CRs in the immune system, using a non-invasive model of SCN circadian arrhythmia. Robust CRs in blood leukocyte trafficking, with a peak during the early light phase (ZT4) and nadir in the early dark phase (ZT18), were absent in arrhythmic hamsters, as were CRs in spleen clock gene (per1, bmal1) expression, indicating that a functional pacemaker in the SCN is required for the generation of CRs in leukocyte trafficking and for driving peripheral clocks in secondary lymphoid organs. Pinealectomy was without effect on CRs in leukocyte trafficking, but abolished CRs in spleen clock gene expression, indicating that nocturnal melatonin secretion is necessary for communicating circadian time information to the spleen. CRs in trafficking of antigen presenting cells (CD11c(+) dendritic cells) in the skin were abolished, and antigen-specific delayed-type hypersensitivity skin inflammatory responses were markedly impaired in arrhythmic hamsters. The SCN drives robust CRs in leukocyte trafficking and lymphoid clock gene expression; the latter of which is not expressed in the absence of melatonin. Robust entrainment of the circadian pacemaker provides a signal critical to diurnal rhythms in immunosurveilliance and optimal memory T-cell dependent immune responses.

Synchronous activation of gonadotropin-releasing hormone gene transcription and secretion by pulsatile kisspeptin stimulation.

Pulsatile release of hypothalamic gonadotropin-releasing hormone (GnRH) is essential for pituitary gonadotrope function. Although the importance of pulsatile GnRH secretion has been recognized for several decades, the mechanisms underlying GnRH pulse generation in hypothalamic neural networks remain elusive. Here, we demonstrate the ultradian rhythm of GnRH gene transcription in single GnRH neurons using cultured hypothalamic slices prepared from transgenic mice expressing a GnRH promoter-driven destabilized luciferase reporter. Although GnRH promoter activity in each GnRH neuron exhibited an ultradian pattern of oscillations with a period of ∼10 h, GnRH neuronal cultures exhibited partially synchronized bursts of GnRH transcriptional activity at ∼2-h intervals. Surprisingly, pulsatile administration of kisspeptin, a potent GnRH secretagogue, evoked dramatic synchronous activation of GnRH gene transcription with robust stimulation of pulsatile GnRH secretion. We also addressed the issue of hierarchical interaction between the circadian and ultradian rhythms by using Bmal1-deficient mice with defective circadian clocks. The circadian molecular oscillator barely affected basal ultradian oscillation of GnRH transcription but was heavily involved in kisspeptin-evoked responses of GnRH neurons. In conclusion, we have clearly shown synchronous bursts of GnRH gene transcription in the hypothalamic GnRH neuronal population in association with episodic neurohormone secretion, thereby providing insight into GnRH pulse generation.

Seasonal changes in cell proliferation in the adult sheep brain and pars tuberalis.

To adapt to seasonal variations in the environment, most mammalian species exhibit seasonal cycles in their physiology and behavior. Seasonal plasticity in the structure and function of the central nervous system contributes to the adaptation of this physiology in seasonal mammals. As part of these plasticity mechanisms, seasonal variations in proliferation rate and neuron production have been extensively studied in songbirds. In this report, we investigated whether this type of brain plasticity also occurs in sheep, a seasonal species, by assessing variations in cell proliferation in the sheep diencephalon. We administered the cell birth marker 5'-bromodeoxyuridine (BrdU) to adult female sheep in July and December, during long and short photoperiod, respectively. The BrdU incorporation was analyzed and quantified in the hypothalamus, a key center for neuroendocrine regulations, as well as in other structures involved in relaying neuroendocrine and sensory information, including the median eminence, the pars tuberalis of the pituitary gland, and the thalamus. In December, 2-fold and 6-fold increases in the number of BrdU+ nuclei were observed in the hypothalamus and thalamus, respectively, when compared with July. This variation is independent of the influence of peripheral gonadal estradiol variations. An inverse seasonal regulation of cell proliferation was observed in the pars tuberalis. In contrast, no seasonal variation in cell proliferation was seen in the subventricular zone of the lateral ventricle. Many of the newborn cells in the adult ovine hypothalamus and thalamus differentiate into neurons and glial cells, as assessed by the expression of neuronal (DCX, NeuN) and glial (GFAP, S100B) fate markers. In summary, we show that the estimated cell proliferation rates in the sheep hypothalamus, thalamus, and pars tuberalis are different between seasons. These variations are independent of the seasonal fluctuations of peripheral estradiol levels, unlike the results described in the brain nuclei involved in song control of avian species.

Luz y Ritmos circadianos: Efectos en la salud y en el desempeño / Circadian rhythms and light: effects on health and performance

Se proporciona una visión global sobre la estructura y funcionamiento del sistema circadiano. Tal visión ayuda a entender mejor los problemas derivados de su mal funcionamiento y cómo compensarlos mediante la terapia lumínica. También se muestra que lo más relevante para la sincronización del sistema circadiano ens la exposición a los ciclos de luz-oscuridad. Se explica por qué los trabajadores nocturnos tiene más problemas de salud. Se explican las diferencias entre la estimulación circadiana y la estimulación visual y a continuación se analiza por qué la fotometría estándar no proporciona mediciones adecuadas para determinar la estimulación que actúa sobre el sistema circadiano. Para terminar, se describen la filosofía de la terapia lumínica y su eficacia para evitar-eliminar problemas asociados al funcionamiento inadecuado del sistema circadiano en lo que tiene que ver con (1) sus activación transitoria, (2) el desajuste entre los relojes circadiano y biológico y (3) la depresión estacional (AU)

A general view on circadian system structure and performance is provided for a better understanding of the problems derived from its malfunction and the ways to compensate for the negative effects using light therapy. The relevance of exposure to light-darkness cycles, in order to synchronies the circadian system, is highlighted and the reasons behind night-shift workers ´ill health are explained. Differences between circadian and visual stimulation are given which relates to the reasons why standard photometry does not provide accurate measurements for the optimum stimulation of the circadian system. Finally, the philosophy of light therapy and its efficacy in avoiding/eliminating problems associated with inaccurate circadian system functioning in reference to (1) its transitory activation, (2) biological and chronological clocks mismatches and (3) seasonal depression, are describeds (AU)