Circadian disruption of feeding-fasting rhythm and its consequences for metabolic, immune, cancer, and cognitive processes.

The circadian system is composed by a central hypothalamic clock at the suprachiasmatic nuclei (SCN) that communicates with peripheral circadian oscillators for daily coordination of behavior and physiology. The SCN entrain to the environmental 24-h light-dark (LD) cycle and drive daily rhythms of internal synchronizers such as core body temperature, hypothalamic-hypophysary hormones, sympathetic/parasympathetic activity, as well as behavioral and feeding-fasting rhythms, which supply signals setting core molecular clocks at central and peripheral tissues. Steady phase relationships between the SCN and peripheral oscillators keep homeostatic processes such as microbiota/microbiome composition/activity, metabolic supply/demand, energy balance, immunoinflammatory process, sleep amount and quality, psychophysiological stress, etc.

Circadian regulation of MGMT expression and promoter methylation underlies daily rhythms in TMZ sensitivity in glioblastoma.

Background: Glioblastoma (GBM) is the most common primary brain tumor in adults. Despite extensive research and clinical trials, median survival post-treatment remains at 15 months. Thus, all opportunities to optimize current treatments and improve patient outcomes should be considered.

Circadian Clock Gene bmal1 Acts as a Tumor Suppressor Gene in a Mice Model of Human Glioblastoma.

Glioblastomas derived from malignant astrocytes are the most common primary tumors of the central nervous system in humans, exhibiting very bad prognosis. Treatment with surgery, radiotherapy, and chemotherapy (mainly using temozolomide), generates as much one-year survival. The circadian clock controls different aspects of tumor development, and its role in GBM is beginning to be explored.

Circadian regulation of expression and promoter methylation underlies daily rhythms in TMZ sensitivity in glioblastoma.

Background: Glioblastoma (GBM) is the most common primary brain tumor in adults. Despite extensive research and clinical trials, median survival post-treatment remains at 15 months. Thus, all opportunities to optimize current treatments and improve patient outcomes should be considered.

Chronic circadian desynchronization of feeding-fasting rhythm generates alterations in daily glycemia, LDL cholesterolemia and microbiota composition in mice.

Introduction: The circadian system synchronizes behavior and physiology to the 24-h light- dark (LD) cycle. Timing of food intake and fasting periods provide strong signals for peripheral circadian clocks regulating nutrient assimilation, glucose, and lipid metabolism. Mice under 12 h light:12 h dark (LD) cycles exhibit behavioral activity and feeding during the dark period, while fasting occurs at rest during light.

Cysteine Oxidation Promotes Dimerization/Oligomerization of Circadian Protein Period 2.

The molecular circadian clock is based on a transcriptional/translational feedback loop in which the stability and half-life of circadian proteins is of importance. Cysteine residues of proteins are subject to several redox reactions leading to S-thiolation and disulfide bond formation, altering protein stability and function. In this work, the ability of the circadian protein period 2 (PER2) to undergo oxidation of cysteine thiols was investigated in HEK-293T cells.

Timing of Novel Drug 1A-116 to Circadian Rhythms Improves Therapeutic Effects against Glioblastoma.

Unlabelled: The Ras homologous family of small guanosine triphosphate-binding enzymes (GTPases) is critical for cell migration and proliferation. The novel drug 1A-116 blocks the interaction site of the Ras-related C3 botulinum toxin substrate 1 (RAC1) GTPase with some of its guanine exchange factors (GEFs), such as T-cell lymphoma invasion and metastasis 1 (TIAM1), inhibiting cell motility and proliferation. Knowledge of circadian regulation of targets can improve chemotherapy in glioblastoma.

Redox and Antioxidant Modulation of Circadian Rhythms: Effects of Nitroxyl, N-Acetylcysteine and Glutathione.

The circadian clock at the hypothalamic suprachiasmatic nucleus (SCN) entrains output rhythms to 24-h light cycles. To entrain by phase-advances, light signaling at the end of subjective night (circadian time 18, CT18) requires free radical nitric oxide (NO•) binding to soluble guanylate cyclase (sGC) heme group, activating the cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG). Phase-delays at CT14 seem to be independent of NO•, whose redox-related species were yet to be investigated.

Role of G-Substrate in the NO/cGMP/PKG Signal Transduction Pathway for Photic Entrainment of the Hamster Circadian Clock.

The mammalian circadian clock at the hypothalamic suprachiasmatic nuclei (SCN) entrains biological rhythms to the 24-h cyclic environment, by encoding light-dark transitions in SCN neurons. Light pulses induce phase shifts in the clock and in circadian rhythms; photic signaling for circadian phase advances involves a nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (PKG) pathway, increasing the expression of Period () genes. Effectors downstream of PKG remain unknown.

Protein Kinases in the Photic Signaling of the Mammalian Circadian Clock.

Circadian clocks drive biological rhythms in physiology and behavior, providing a selective advantage by enabling organisms to synchronize to the 24 h environmental day. This process depends on light-dark transitions as the main signal that shifts the phase of the clock. In mammals, the light input reaches the master circadian clock in the hypothalamic suprachiasmatic nucleus through glutamatergic afferents from the retina, resulting in phase-shifts of the overt rhythms which depend on the time of the day at which light is applied, leading to changes in the activity of circadian core clock genes (, ).

Don't just say no: Differential pathways and pharmacological responses to diverse nitric oxide donors.

Nitric oxide (NO) is a gaseous free radical molecule with a short half-life (∼1 s), which can gain or lose an electron into three interchangeable redox-dependent forms, the radical (NO), the nitrosonium cation (NO), and nitroxyl anion (HNO). NO acts as an intra and extracellular signaling molecule regulating a wide range of functions in the cardiovascular, immune, and nervous system. NO donors are collectively known by their ability to release NOin vitro and in vivo, being proposed as therapeutic pharmacological tools for the treatment of several pathologies, such as cardiovascular disease.

Circadian and Metabolic Effects of Light: Implications in Weight Homeostasis and Health.

Daily interactions between the hypothalamic circadian clock at the suprachiasmatic nucleus (SCN) and peripheral circadian oscillators regulate physiology and metabolism to set temporal variations in homeostatic regulation. Phase coherence of these circadian oscillators is achieved by the entrainment of the SCN to the environmental 24-h light:dark (LD) cycle, coupled through downstream neural, neuroendocrine, and autonomic outputs. The SCN coordinate activity and feeding rhythms, thus setting the timing of food intake, energy expenditure, thermogenesis, and active and basal metabolism.

Effects of chronic forced circadian desynchronization on body weight and metabolism in male mice.

Metabolic functions are synchronized by the circadian clock setting daily patterns of food intake, nutrient delivery, and behavioral activity. Here, we study the impact of chronic jet-lag (CJL) on metabolism, and test manipulations aimed to overcome potential alterations. We recorded weight gain in C57Bl/6 mice under chronic 6 h advances or delays of the light-dark cycle every 2 days (ChrA and ChrD, respectively).

N-nitrosomelatonin enhances photic synchronization of mammalian circadian rhythms.

Most physiological processes in mammals are synchronized to the daily light:dark cycle by a circadian clock located in the hypothalamic suprachiasmatic nucleus. Signal transduction of light-induced phase advances of the clock is mediated through a neuronal nitric oxide synthase-guanilyl cyclase pathway. We have employed a novel nitric oxide-donor, N-nitrosomelatonin, to enhance the photic synchronization of circadian rhythms in hamsters.

Ecological segregation in space, time and trophic niche of sympatric planktivorous petrels.

The principle of competitive exclusion postulates that ecologically-similar species are expected to partition their use of resources, leading to niche divergence. The most likely mechanisms allowing such coexistence are considered to be segregation in a horizontal, vertical or temporal dimension, or, where these overlap, a difference in trophic niche. Here, by combining information obtained from tracking devices (geolocator-immersion and time depth recorders), stable isotope analyses of blood, and conventional morphometry, we provide a detailed investigation of the ecological mechanisms that explain the coexistence of four species of abundant, zooplanktivorous seabirds in Southern Ocean ecosystems (blue petrel Halobaena caerulea, Antarctic prion Pachyptila desolata, common diving petrel Pelecanoides urinatrix and South Georgian diving petrel P.

The times they're a-changing: effects of circadian desynchronization on physiology and disease.

Circadian rhythms are endogenous and need to be continuously entrained (synchronized) with the environment. Entrainment includes both coupling internal oscillators to external periodic changes as well as synchrony between the central clock and peripheral oscillators, which have been shown to exhibit different phases and resynchronization speed. Temporal desynchronization induces diverse physiological alterations that ultimately decrease quality of life and induces pathological situations.

Forced desynchronization of activity rhythms in a model of chronic jet lag in mice.

We studied locomotor activity rhythms of C57/Bl6 mice under a chronic jet lag (CJL) protocol (ChrA(6/2) ), which consisted of 6-hour phase advances of the light-dark schedule (LD) every 2 days. Through periodogram analysis, we found 2 components of the activity rhythm: a short-period component (21.01 ± 0.

Light intensity determines temporal niche switching of behavioral activity in deep-water Nephrops norvegicus (Crustacea: Decapoda).

The temporal distribution of behavioral programs throughout the 24-h day, known as temporal niche of a species, is determined by ecological factors that directly affect the adaptive value of the timing of specific behaviors. Temporal niche switching has been described in several species and is likely adaptive in habitats where the daily timing of those factors changes. Benthic species whose habitats span a wide range of water depths are exposed to considerable depth-dependent environmental changes.

Circadian entrainment to light-dark cycles involves extracellular nitric oxide communication within the suprachiasmatic nuclei.

The ability to synchronize to light-dark (LD) cycles is an essential property of the circadian clock, located in mammals within the hypothalamic suprachiasmatic nuclei (SCN). Single light pulses activate nitric oxide (NO) intracellular signaling, leading to circadian phase-shifts required for synchronization. In addition, extracellular NO has a role in the SCN paracrine communication of photic phase advances.

Arrhythmic rats after SCN lesions and constant light differ in short time scale regulation of locomotor activity.

Circadian rhythm disruption (i.e., arrhythmicity) in motor activity is an abnormal behavioral pattern.

Effects of transient and continuous wheel running activity on the upper and lower limits of entrainment to light-dark cycles in female hamsters.

The entrainment limits to light-dark cycles can be modified by the experimental conditions under which they are tested. Among the factors that may influence entrainment is the amount of wheel running exerted by the animal. In the present work, the effects of transitory and continuous wheel running on entrainment to light-dark cycles were tested using a range of T cycles at the entrainment limits.

Method for studying behavioural activity patterns during long-term recordings using a force-plate actometer.

The motor activity (MA) patterns of rodents are commonly detected in the laboratory using infrared photo-beams or running wheels. In chronobiological studies, the MA rhythm is considered as a behavioural output of the circadian pacemaker. This paper describes a method to obtain long-term records of MA in rodents, with a 1mm spatial resolution and a 1s temporal resolution.

Effect of melatonin and diazepam on the dissociated circadian rhythm in rats.

The main structures involved in the circadian system in mammals are the suprachiasmatic nuclei (SCN) of the hypothalamus. The SCN contain multiple autonomous single-cell circadian oscillators that are coupled among themselves, generating a single rhythm. However, under determined circumstances, the oscillators may uncouple and generate several rhythmic patterns.