Browse
Submit Data
Databases
API
Help

Dataset Information

20 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Influence of Schizophrenia-Associated Gene Egr3 on Sleep Behavior and Circadian Rhythms in Mice.

ABSTRACT: Up to 80% of people meeting DSM-IV definitions for schizophrenia will exhibit difficulties with sleep, along with a breakdown in circadian entrainment and rhythmicity. The changes to the sleep and circadian systems in this population are thought to be interdependent, as evidenced by the frequent use of the combined term "sleep and circadian rhythm disruption" or "SCRD" to describe their occurrence. To understand links between sleep and circadian problems in the schizophrenia population, we analyzed the duration and rhythmicity of sleep behavior in mice lacking function of the immediate early gene early growth response 3 ( Egr3). EGR3 has been associated with schizophrenia risk in humans, and Egr3-deficient (-/-) mice display various features of schizophrenia that are responsive to antipsychotic treatment. While Egr3-/- mice slept less than their wildtype (WT) littermates, they showed no evidence of circadian disorganization; in fact, circadian rhythms of activity were more robust in these mice compared with WT, as measured by time series analysis and the relative amplitude index of Van Someren's suite of non-parametric circadian rhythm analyses. Differences in circadian robustness were maintained when the animals were transferred to several weeks of housing under constant darkness or constant light. Together, our results suggest that Egr3-/- mice retain control over the circadian timekeeping of sleep and wake, while showing impaired sleep. The findings are compatible with those from a surprising array of mouse models of schizophrenia and raise the possibility that SCRD may be 2 separate disorders in the schizophrenia population requiring different treatment strategies.

SUBMITTER: Maple AM

PROVIDER: S-EPMC8651219 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Influence of EGR3 Transfection on Imaging and Behavior in Rats and Therapeutic Effect of Risperidone in Schizophrenia Model.

Project description:Schizophrenia is a type of neurodevelopmental psychiatric disorder. However, to date, scientists have not discovered the etiology and effective treatment of this condition. We injected the early growth response gene (EGR3) into the bilateral hippocampus to build a schizophrenia rat model. Behavioral phenotyping and resting-state functional magnetic resonance imaging (rs-fMRI) were used to analyze the behavioral and cerebral alterations in the schizophrenia rat model. The efficacy of risperidone therapy was also evaluated. We divided 34 rats into four groups: schizophrenia model group (E group), sham-operation group (FE group), healthy control group (H group), and risperidone therapy group (T group). Open field test and Morris water maze were conducted as behavioral experiments. Next, we performed rs-fMRI after four weeks of EGR3 transfection and risperidone treatment and analyzed imaging data using regional homogeneity (ReHo), the amplitude of low-frequency fluctuations (ALFF), and functional connectivity (FC). We examined the difference in behavioral and neural activation among the four groups and considered the correlations between behavior and imaging results. EGR3 gene transfection decreased the total moved distance in the open field test and the duration in the Q5 zone of the Morris water maze. Risperidone treatment reversed the trend and improved the performance of rats in these behavioral tests. Schizophrenia induced several neural alterations in ALFF and ReHo metrics of the rat brain, and risperidone could partly reverse these alterations. The results suggest that similar research is required for schizophrenia and that risperidone may be a novel treatment for dysregulated neural activation in schizophrenia.

| S-EPMC7542223 | biostudies-literature

Attenuated circadian rhythms in mice lacking the prokineticin 2 gene.

Project description:Circadian clocks drive daily rhythms in virtually all organisms. In mammals, the suprachiasmatic nucleus (SCN) is recognized as the master clock that synchronizes central and peripheral oscillators to evoke circadian rhythms of diverse physiology and behavior. How the timing information is transmitted from the SCN clock to generate overt circadian rhythms is essentially unknown. Prokineticin 2 (PK2), a clock-controlled gene that encodes a secreted protein, has been indicated as a candidate SCN clock output signal that regulates circadian locomotor rhythm. Here we report the generation and analysis of PK2-null mice. The reduction of locomotor rhythms in PK2-null mice was apparent in both hybrid and inbred genetic backgrounds. PK2-null mice also displayed significantly reduced rhythmicity for a variety of other physiological and behavioral parameters, including sleep-wake cycle, body temperature, circulating glucocorticoid and glucose levels, as well as the expression of peripheral clock genes. In addition, PK2-null mice showed accelerated acquisition of food anticipatory activity during a daytime food restriction. We conclude that PK2, acting as a SCN output factor, is important for the maintenance of robust circadian rhythms.

| S-EPMC2713041 | biostudies-other

Circadian gene variants influence sleep and the sleep electroencephalogram in humans.

Project description:The sleep electroencephalogram (EEG) is highly heritable in humans and yet little is known about the genetic basis of inter-individual differences in sleep architecture. The aim of this study was to identify associations between candidate circadian gene variants and the polysomnogram, recorded under highly controlled laboratory conditions during a baseline, overnight, 8 h sleep opportunity. A candidate gene approach was employed to analyze single-nucleotide polymorphisms from five circadian-related genes in a two-phase analysis of 84 healthy young adults (28 F; 23.21 ± 2.97 years) of European ancestry. A common variant in Period2 (PER2) was associated with 20 min less slow-wave sleep (SWS) in carriers of the minor allele than in noncarriers, representing a 22% reduction in SWS duration. Moreover, spectral analysis in a subset of participants (n = 37) showed the same PER2 polymorphism was associated with reduced EEG power density in the low delta range (0.25-1.0 Hz) during non-REM sleep and lower slow-wave activity (0.75-4.5 Hz) in the early part of the sleep episode. These results indicate the involvement of PER2 in the homeostatic process of sleep. Additionally, a rare variant in Melatonin Receptor 1B was associated with longer REM sleep latency, with minor allele carriers exhibiting an average of 65 min (87%) longer latency from sleep onset to REM sleep, compared to noncarriers. These findings suggest that circadian-related genes can modulate sleep architecture and the sleep EEG, including specific parameters previously implicated in the homeostatic regulation of sleep.

| S-EPMC5267557 | biostudies-literature

The genetics of circadian rhythms, sleep and health.

Project description:Circadian rhythms are 24-h rhythms in physiology and behaviour generated by molecular clocks, which serve to coordinate internal time with the external world. The circadian system is a master regulator of nearly all physiology and its disruption has major consequences on health. Sleep and circadian rhythm disruption (SCRD) is a ubiquitous feature in today's 24/7 society, and studies on shift-workers have shown that SCRD can lead not only to cognitive impairment, but also metabolic syndrome and psychiatric illness including depression (1,2). Mouse models of clock mutants recapitulate these deficits, implicating mechanistic and causal links between SCRD and disease pathophysiology (3-5). Importantly, treating clock disruption reverses and attenuates these adverse health states in animal models (6,7), thus establishing the circadian system as a novel therapeutic target. Significantly, circadian and clock-controlled gene mutations have recently been identified by Genome-Wide Association Studies (GWAS) in the aetiology of sleep, mental health and metabolic disorders. This review will focus upon the genetics of circadian rhythms in sleep and health.

| S-EPMC5886477 | biostudies-literature

Modeling the Influence of Chronic Sleep Restriction on Cortisol Circadian Rhythms, with Implications for Metabolic Disorders.

Project description:Chronic sleep deficiency is prevalent in modern society and is associated with increased risk of metabolic and other diseases. While the mechanisms by which chronic sleep deficiency induces pathophysiological changes are yet to be elucidated, the hypothalamic-pituitary-adrenal (HPA) axis may be an important mediator of these effects. Cortisol, the primary hormone of the HPA axis, exhibits robust circadian rhythmicity and is moderately influenced by sleep and wake states and other physiology. Several studies have explored the effects of acute or chronic sleep deficiency (i.e., usually from self-selected chronic sleep restriction, CSR) on the HPA axis. Quantifying long-term changes in the circadian rhythm of cortisol under CSR in controlled conditions is inadequately studied due to practical limitations. We use a semi-mechanistic mathematical model of the HPA axis and the sleep/wake cycle to explore the influence of CSR on cortisol circadian rhythmicity. In qualitative agreement with experimental findings, model simulations predict that CSR results in physiologically relevant disruptions in the phase and amplitude of the cortisol rhythm. The mathematical model presented in this work provides a mechanistic framework to further explore how CSR might lead to HPA axis disruption and subsequent development of chronic metabolic complications.

| S-EPMC8400645 | biostudies-literature

Disrupted circadian rhythms in a mouse model of schizophrenia

Project description:Disrupted circadian rhythms in a mouse model of schizophrenia

2012-03-01 | E-MEXP-3493 | biostudies-arrayexpress

Disrupted circadian rhythms in a mouse model of schizophrenia.

Project description:Sleep and circadian rhythm disruption has been widely observed in neuropsychiatric disorders including schizophrenia [1] and often precedes related symptoms [2]. However, mechanistic basis for this association remains unknown. Therefore, we investigated the circadian phenotype of blind-drunk (Bdr), a mouse model of synaptosomal-associated protein (Snap)-25 exocytotic disruption that displays schizophrenic endophenotypes modulated by prenatal factors and reversible by antipsychotic treatment [3, 4]. Notably, SNAP-25 has been implicated in schizophrenia from genetic [5-8], pathological [9-13], and functional studies [14-16]. We show here that the rest and activity rhythms of Bdr mice are phase advanced and fragmented under a light/dark cycle, reminiscent of the disturbed sleep patterns observed in schizophrenia. Retinal inputs appear normal in mutants, and clock gene rhythms within the suprachiasmatic nucleus (SCN) are normally phased both in vitro and in vivo. However, the 24 hr rhythms of arginine vasopressin within the SCN and plasma corticosterone are both markedly phase advanced in Bdr mice. We suggest that the Bdr circadian phenotype arises from a disruption of synaptic connectivity within the SCN that alters critical output signals. Collectively, our data provide a link between disruption of circadian activity cycles and synaptic dysfunction in a model of neuropsychiatric disease.

| S-EPMC3356578 | biostudies-literature

"Cancersensor": Circadian Rhythms

Project description:Observational, non randomized study aimed at measuring the circadian rhythms in the urinary concentrations of physiological modified nucleosides in 30 patients with metastatic colorectal cancer and in 30 age and sex-matched healthy subjects.

| 2132582 | ecrin-mdr-crc

Sleep Disturbance in Bipolar Disorder: Neuroglia and Circadian Rhythms.

Project description:The worldwide prevalence of sleep disorders is approximately 50%, with an even higher occurrence in a psychiatric population. Bipolar disorder (BD) is a severe mental illness characterized by shifts in mood and activity. The BD syndrome also involves heterogeneous symptomatology, including cognitive dysfunctions and impairments of the autonomic nervous system. Sleep abnormalities are frequently associated with BD and are often a good predictor of a mood swing. Preservation of stable sleep-wake cycles is therefore a key to the maintenance of stability in BD, indicating the crucial role of circadian rhythms in this syndrome. The symptom most widespread in BD is insomnia, followed by excessive daytime sleepiness, nightmares, difficulty falling asleep or maintaining sleep, poor sleep quality, sleep talking, sleep walking, and obstructive sleep apnea. Alterations in the structure or duration of sleep are reported in all phases of BD. Understanding the role of neuroglia in BD and in various aspects of sleep is in nascent state. Contributions of the different types of glial cells to BD and sleep abnormalities are discussed in this paper.

| S-EPMC6656854 | biostudies-literature

Neonicotinoids disrupt circadian rhythms and sleep in honey bees.

Project description:Honey bees are critical pollinators in ecosystems and agriculture, but their numbers have significantly declined. Declines in pollinator populations are thought to be due to multiple factors including habitat loss, climate change, increased vulnerability to disease and parasites, and pesticide use. Neonicotinoid pesticides are agonists of insect nicotinic cholinergic receptors, and sub-lethal exposures are linked to reduced honey bee hive survival. Honey bees are highly dependent on circadian clocks to regulate critical behaviors, such as foraging orientation and navigation, time-memory for food sources, sleep, and learning/memory processes. Because circadian clock neurons in insects receive light input through cholinergic signaling we tested for effects of neonicotinoids on honey bee circadian rhythms and sleep. Neonicotinoid ingestion by feeding over several days results in neonicotinoid accumulation in the bee brain, disrupts circadian rhythmicity in many individual bees, shifts the timing of behavioral circadian rhythms in bees that remain rhythmic, and impairs sleep. Neonicotinoids and light input act synergistically to disrupt bee circadian behavior, and neonicotinoids directly stimulate wake-promoting clock neurons in the fruit fly brain. Neonicotinoids disrupt honey bee circadian rhythms and sleep, likely by aberrant stimulation of clock neurons, to potentially impair honey bee navigation, time-memory, and social communication.

| S-EPMC7578099 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data