Reproductive hormones and sex chromosomes drive sex differences in the sleep-wake cycle.

There are well-documented gender differences in the risk and severity of sleep disorders and associated comorbidities. While fundamental sex differences in sleep regulatory mechanisms may contribute to gender disparities, biological responses to sleep loss and stress may underlie many of the risks for sleep disorders in women and men. Some of these sex differences appear to be dependent on sex chromosome complement (XX or XY) and the organizational effects of reproductive hormones.

Environmental circadian disruption re-writes liver circadian proteomes.

Circadian gene expression is fundamental to the establishment and functions of the circadian clock, a cell-autonomous and evolutionary-conserved timing system. Yet, how it is affected by environmental-circadian disruption (ECD) such as shiftwork and jetlag are ill-defined. Here, we provided a comprehensive and comparative description of male liver circadian gene expression, encompassing transcriptomes, whole-cell proteomes and nuclear proteomes, under normal and after ECD conditions.

Environmental circadian disruption re-programs liver circadian gene expression.

Circadian gene expression is fundamental to the establishment and functions of the circadian clock, a cell-autonomous and evolutionary-conserved timing system. Yet, how it is affected by environmental-circadian disruption (ECD) such as shiftwork and jetlag, which impact millions of people worldwide, are ill-defined. Here, we provided the first comprehensive description of liver circadian gene expression under normal and after ECD conditions.

Arginine-vasopressin-expressing neurons in the murine suprachiasmatic nucleus exhibit a circadian rhythm in network coherence in vivo.

The suprachiasmatic nucleus (SCN) is composed of functionally distinct subpopulations of GABAergic neurons which form a neural network responsible for synchronizing most physiological and behavioral circadian rhythms in mammals. To date, little is known regarding which aspects of SCN rhythmicity are generated by individual SCN neurons, and which aspects result from neuronal interaction within a network. Here, we utilize in vivo miniaturized microscopy to measure fluorescent GCaMP-reported calcium dynamics in arginine vasopressin (AVP)-expressing neurons in the intact SCN of awake, behaving mice.

Non-rapid eye movement sleep determines resilience to social stress.

Resilience, the ability to overcome stressful conditions, is found in most mammals and varies significantly among individuals. A lack of resilience can lead to the development of neuropsychiatric and sleep disorders, often within the same individual. Despite extensive research into the brain mechanisms causing maladaptive behavioral-responses to stress, it is not clear why some individuals exhibit resilience.

"The ubiquitin ligase SIAH2 is a female-specific regulator of circadian rhythms and metabolism".

Circadian clocks enable organisms to predict and align their behaviors and physiologies to constant daily day-night environmental cycle. Because the ubiquitin ligase Siah2 has been identified as a potential regulator of circadian clock function in cultured cells, we have used SIAH2-deficient mice to examine its function in vivo. Our experiments demonstrate a striking and unexpected sexually dimorphic effect of SIAH2-deficiency on the regulation of rhythmically expressed genes in the liver.

Angelman syndrome and melatonin: What can they teach us about sleep regulation.

In 1965, Dr Harry Angelman reported a neurodevelopmental disorder affecting three unrelated children who had similar symptoms: brachycephaly, mental retardation, ataxia, seizures, protruding tongues, and remarkable paroxysms of laughter. Over the past 50 years, the disorder became Angelman's namesake and symptomology was expanded to include hyper-activity, stereotypies, and severe sleep disturbances. The sleep disorders in many Angelman syndrome (AS) patients are broadly characterized by difficulty falling and staying asleep at night.

M100907 and BD 1047 attenuate the acute toxic effects of methamphetamine.

There are no Food and Drug Administration approved pharmacotherapies for methamphetamine (METH) overdose, thus identifying novel drug targets to prevent this devastating adverse event is a public-health imperative. Previous research suggests that serotonin and sigma receptors may contribute to the adverse effects of METH. The present study assessed whether pretreatment with the 5-HT receptor antagonist M100907 or the sigma 1 (σ) receptor antagonist BD 1047 attenuated METH-induced lethality, hyperthermia, convulsions, and seizures.

Nitrergic neurons of the dorsal raphe nucleus encode information about stress duration.

Nitrergic neurons of the dorsal raphe nucleus (DRN) may play a role in physiological stress responses. The caudal lateral wings (CLW) are unique compared to other rostral-caudal DRN sub-regions because they contain distinct nitric oxide (NO) synthase (NOS) populations that are independent of tryptophan hydroxylase (TPH). NOS neurons in the CLW are also highly activated during acute restraint stress.

function in skeletal muscle regulates sleep.

Sleep loss can severely impair the ability to perform, yet the ability to recover from sleep loss is not well understood. Sleep regulatory processes are assumed to lie exclusively within the brain mainly due to the strong behavioral manifestations of sleep. Whole-body knockout of the circadian clock gene in mice affects several aspects of sleep, however, the cells/tissues responsible are unknown.

Homeostatic effects of exercise and sleep on metabolic processes in mice with an overexpressed skeletal muscle clock.

Brain and muscle-ARNT-like factor (Bmal1/BMAL1) is an essential transcriptional/translational factor of circadian clocks. Loss of function of Bmal1/BMAL1 is highly disruptive to physiological and behavioral processes. In light of these previous findings, we examined if transgenic overexpression of Bmal1/BMAL1 in skeletal muscle could alter metabolic processes.

Sleep Is Critical for Remote Preconditioning-Induced Neuroprotection.

Study Objectives: Episodes of brief limb ischemia (remote preconditioning) in mice induce tolerance to modeled ischemic stroke (focal brain ischemia). Since stroke outcomes are in part dependent on sleep-wake history, we sought to determine if sleep is critical for the neuroprotective effect of limb ischemia.

Methods: EEG/EMG recording electrodes were implanted in mice.

Maternal Ube3a Loss Disrupts Sleep Homeostasis But Leaves Circadian Rhythmicity Largely Intact.

Unlabelled: Individuals with Angelman syndrome (AS) suffer sleep disturbances that severely impair quality of life. Whether these disturbances arise from sleep or circadian clock dysfunction is currently unknown. Here, we explored the mechanistic basis for these sleep disorders in a mouse model of Angelman syndrome (Ube3a(m-/p+) mice).

Sustained activation of GABAA receptors in the suprachiasmatic nucleus mediates light-induced phase delays of the circadian clock: a novel function of ionotropic receptors.

The suprachiasmatic nucleus (SCN) contains a circadian clock that generates endogenous rhythmicity and entrains that rhythmicity with the day-night cycle. The neurochemical events that transduce photic input within the SCN and mediate entrainment by resetting the molecular clock have yet to be defined. Because GABA is contained in nearly all SCN neurons we tested the hypothesis that GABA serves as this signal in studies employing Syrian hamsters (Mesocricetus auratus).

Analysis and measurement of the sympathetic and sensory innervation of white and brown adipose tissue.

Here, we provide a detailed account of how to denervate white and brown adipose tissue (WAT and BAT) and how to measure sympathetic nervous system (SNS) activity to these and other tissues neurochemically. The brain controls many of the functions of WAT and BAT via the SNS innervation of the tissues, especially lipolysis and thermogenesis, respectively. There is no clearly demonstrated parasympathetic innervation of WAT or the major interscapular BAT (IBAT) depot.

Period-amplitude analysis reveals wake-dependent changes in the electroencephalogram during sleep deprivation.

Study Objectives: Electroencephalographic slow wave activity (SWA) during non-rapid eye movement (NREM) sleep results from the synchronous oscillation of cortical neurons and is the standard measurement of sleep homeostasis. SWA is not a direct measure of sleep pressure accumulation, but rather a measure of the NREM-sleep response to accumulated sleep pressure. Currently, no practical standard for the direct measurement of sleep pressure accumulation exists.

Sleep loss and the inflammatory response in mice under chronic environmental circadian disruption.

Shift work and trans-time zone travel lead to insufficient sleep and numerous pathologies. Here, we examined sleep/wake dynamics during chronic exposure to environmental circadian disruption (ECD), and if chronic partial sleep loss associated with ECD influences the induction of shift-related inflammatory disorder. Sleep and wakefulness were telemetrically recorded across three months of ECD, in which the dark-phase of a light-dark cycle was advanced weekly by 6 h.

Sex chromosomes regulate nighttime sleep propensity during recovery from sleep loss in mice.

Sex differences in spontaneous sleep amount are largely dependent on reproductive hormones; however, in mice some sex differences in sleep amount during the active phase are preserved after gonadectomy and may be driven by non-hormonal factors. In this study, we sought to determine whether or not these sex differences are driven by sex chromosome complement. Mice from the four core genotype (FCG) mouse model, whose sex chromosome complement (XY, XX) is independent of phenotype (male or female), were implanted with electroencephalographic (EEG) and electromyographic (EMG) electrodes for the recording of sleep-wake states and underwent a 24-hr baseline recording followed by six hours of forced wakefulness.

Altered sleep regulation in a mouse model of SCN1A-derived genetic epilepsy with febrile seizures plus (GEFS+).

Purpose: Mutations in the voltage-gated sodium channel (VGSC) gene SCN1A are responsible for a number of epilepsy disorders, including genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome. In addition to seizures, patients with SCN1A mutations often experience sleep abnormalities, suggesting that SCN1A may also play a role in the neuronal pathways involved in the regulation of sleep. However, to date, a role for SCN1A in the regulation of sleep architecture has not been directly examined.

Dysregulation of inflammatory responses by chronic circadian disruption.

Circadian rhythms modulate nearly every mammalian physiological process. Chronic disruption of circadian timing in shift work or during chronic jet lag in animal models leads to a higher risk of several pathologies. Many of these conditions in both shift workers and experimental models share the common risk factor of inflammation.

Chronic sleep deprivation markedly reduces coagulation factor VII expression.

Chronic sleep loss, a common feature of human life in industrialized countries, is associated to cardiovascular disorders. Variations in functional parameters of coagulation might contribute to explain this relationship. By exploiting the mouse model and a specifically designed protocol, we demonstrated that seven days of partial sleep deprivation significantly decreases (-30.

Regulation of light's action in the mammalian circadian clock: role of the extrasynaptic GABAA receptor.

GABA(A) receptor agonists act in the suprachiasmatic nucleus (SCN) to reset circadian rhythms during the day but inhibit the ability of light to reset rhythms during the night. In the present study, we examined whether these paradoxical differences in the effect of GABA(A) receptor stimulation on the circadian system are mediated by separate GABA(A) receptor subtypes. 4,5,6,7-Tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), a GABA(A) receptor agonist, preferentially activates GABA(A) receptors in extrasynaptic locations.

Interactions of GABA A receptor activation and light on period mRNA expression in the suprachiasmatic nucleus.

Activation of gamma-aminobutyric acid (GABA) A receptors in the suprachiasmatic nucleus (SCN) resets the circadian clock during the day and inhibits the ability of light to reset the clock at night. Light in turn acts during the day to inhibit the phase-resetting effects of GABA. Some evidence suggests that Period mRNA changes in the SCN are responsible for these interactions between light and GABA.

Light and GABA)(A) receptor activation alter period mRNA levels in the SCN of diurnal Nile grass rats.

We examined Period (Per) mRNA rhythms in the suprachiasmatic nucleus (SCN) of a diurnal rodent and assessed how phase-shifting stimuli acutely affect SCN Per mRNA using semiquantitative in situ hybridization. First, Per1 and Per2 varied rhythmically in the SCN over the course of one circadian cycle in constant darkness: Per1 mRNA was highest in the early to mid-subjective day, while Per2 mRNA levels peaked in the late subjective day. Second, acute light exposure in the early subjective night significantly increased both Per1 and Per2 mRNA.