Multi-brain-region transcriptional organization linking sleep and affective functions
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ABSTRACT:
PROVIDER: PRJNA429653 | ENA |
REPOSITORIES: ENA
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Project description:Sleep and affective behaviors are highly interrelated phenotypes, commonly altered in a variety of neuropsychiatric diseases, including major depressive disorder (MDD). To understand the transcriptomic organization underlying sleep and affective function, we studied a population of (C57BL/6J x 129S1/SvImJ) F2 mice by measuring 283 affective and sleep phenotypes and profiling gene expression across four brain regions, including the frontal cortex, hippocampus, thalamus, and hypothalamus. We identified converging molecular bases for sleep and affective phenotypes at both the single-gene and gene-network levels. Utilizing publicly available transcriptomic datasets collected from sleep-deprived mice and major depressive disorder (MDD) patients, we identified three cortical gene networks altered by sleep/wake changes and depression. The network-level actions of sleep loss and depression were opposite to each other, providing a mechanistic basis for the sleep disruptions commonly observed in depression as well as the reported acute antidepressant effects of sleep deprivation. We highlight one particular network composed of circadian rhythm regulators and neuronal activity-dependent immediate-early genes. The key upstream driver of this network, Arc, may act as a nexus linking sleep and depression. Our data provide mechanistic insights into the role of sleep in affective function and MDD.
2018-12-21 | GSE109112 | GEO
Project description:Sleep dysfunction and stress susceptibility are co-morbid complex traits, which often precede and predispose patients to a variety of neuropsychiatric diseases. Here, we demonstrate multi-level organizations of genetic landscape, candidate genes, and molecular networks associated with 328 stress and sleep traits in a chronically stressed population of 338 (C57BL/6J×A/J) F2 mice. We constructed striatal gene co-expression networks, revealing functionally and cell-type-specific gene co-regulations important for stress and sleep. Using a composite ranking system, we identified network modules most relevant for 15 independent phenotypic categories, highlighting a mitochondria/synaptic module that links sleep and stress. The key network regulators of this module are overrepresented with genes implicated in neuropsychiatric diseases. Our work suggests the interplay between sleep, stress, and neuropathology emerge from genetic influences on gene expression and their collective organization through complex molecular networks, providing a framework to interrogate the mechanisms underlying sleep, stress susceptibility, and related neuropathology. Examination of genomic and transcriptomic networks in a random subset of 100 (B6xA/J)F2 mice modeling the natural spectrum of stress susceptibility.
2015-01-08 | E-GEOD-60312 | biostudies-arrayexpress
Project description:Sleep dysfunction and stress susceptibility are co-morbid complex traits, which often precede and predispose patients to a variety of neuropsychiatric diseases. Here, we demonstrate multi-level organizations of genetic landscape, candidate genes, and molecular networks associated with 328 stress and sleep traits in a chronically stressed population of 338 (C57BL/6J×A/J) F2 mice. We constructed striatal gene co-expression networks, revealing functionally and cell-type-specific gene co-regulations important for stress and sleep. Using a composite ranking system, we identified network modules most relevant for 15 independent phenotypic categories, highlighting a mitochondria/synaptic module that links sleep and stress. The key network regulators of this module are overrepresented with genes implicated in neuropsychiatric diseases. Our work suggests the interplay between sleep, stress, and neuropathology emerge from genetic influences on gene expression and their collective organization through complex molecular networks, providing a framework to interrogate the mechanisms underlying sleep, stress susceptibility, and related neuropathology.
2015-01-08 | GSE60312 | GEO
Project description:<p>Chronic sleep loss profoundly impacts metabolic health and shortens lifespan, but studies of the mechanisms involved have focused largely on acute sleep deprivation. To identify metabolic consequences of chronically reduced sleep, we conducted unbiased metabolomics on heads of three adult Drosophila short-sleeping mutants with very different mechanisms of sleep loss: fumin (fmn), redeye (rye), and sleepless (sss). Common features included elevated ornithine and polyamines, with lipid, acyl-carnitine, and TCA cycle changes suggesting mitochondrial dysfunction. Studies of excretion demonstrate inefficient nitrogen elimination in adult sleep mutants, likely contributing to their polyamine accumulation. Increasing levels of polyamines, particularly putrescine, promote sleep in control flies but poison sleep mutants. This parallels the broadly enhanced toxicity of high dietary nitrogen load from protein in chronically sleep-restricted Drosophila, including both sleep mutants and flies with hyper-activated wake-promoting neurons. Together, our results implicate nitrogen stress as a novel mechanism linking chronic sleep loss to adverse health outcomes-and perhaps for linking food and sleep homeostasis at the cellular level in healthy organisms.</p>
2023-03-18 | MTBLS3318 | MetaboLights
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2024-08-26 | GSE248193 | GEO
Project description:Sleep loss regulates gene expression throughout the brain and impacts learning and memory. However, the molecular consequences of sleep deprivation and the ability of subsequent sleep (recovery sleep) to restore baseline gene expression remain underexplored. Our goal here is to overview transcriptional changes at the gene level in the cortex of adult male wildtype mice in response to sleep loss and recovery sleep. This dataset constitutes an integration of novel data with two publicly available RNA-seq studies and contains 3, 5, and 6 hours of sleep deprivation and 2 and 6 hours of recovery sleep time points.
2024-08-19 | GSE237419 | GEO
Project description:Analysis of the effects of sleep deprivation, recovery sleep, and three time-of-day controls on seven brain regions laser microdissected from mouse brain. The regions include the locus coeruleus, suprachiasmatic nucleus, hypocretin area, tuberomammillary nucleus, orbital cortex, posteromedial cortical amygdala, and entorhinal cortex. In this study, 7 brain regions were collected by laser microdissection from brain tissue of mice from 5 different treatment groups and used for microarray experiments. Four biological replicates were generated for each regionxcondition. Conditions are: SD, sleep deprivation for 6 hours from ZT0 - 6; SDC, time-of-day control for SD at ZT6; RS, recovery sleep for 4 hours following SD; RSC, time-of-day control for RS at ZT10; W, spontaneous waking at ZT18.
2010-08-16 | E-GEOD-23628 | biostudies-arrayexpress
Project description:Disruption of sleep and circadian rhythms are a comorbid feature of many pathologies, and can negatively influence many health conditions, including degenerative disease, metabolic illness, cancer, and various neurological disorders. Genetic association studies linking sleep and circadian disturbances with disease susceptibility have mainly focused on changes in gene expression due to mutations, such as single-nucleotide polymorphisms. The interaction between sleep and/or circadian rhythms with the use of Alternative Polyadenylation (APA) has been largely undescribed, particularly in the context of other disorders. APA is a process that generates various transcript isoforms of the same gene affecting its mRNA translation, stability, localization, and subsequent function. Here we identified unique polyadenylation sites (PASs) expressed in rat brain over time-of-day, immediately following sleep deprivation, and the subsequent recovery period. From these data, we performed a meta-analysis of sleep- or circadian-associated PASs with recently described APA-linked brain disorder susceptibility genes.
2023-12-25 | GSE250324 | GEO
Project description:Although at the organismal level sleep is defined as a behavioral state, at the level of the cerebral cortex sleep has a distinct local and use-dependent aspect. This observation raises the question whether sleep is a functional property of a complex brain or occurs at the level of neuronal assemblies with populations that were active more during wakefulness needing more intense sleep to recover. Here we show that primary cortical cultures have the capacity to change between sleep- and wake-like states that share key signatures with their in vivo counterparts. Cortical cultures initially exhibit random firing activity that is gradually replaced by a M-bM-^@M-^\sleep-likeM-bM-^@M-^] synchronized burst-pause firing activity as neurons mature and make connections. When stimulated with excitatory neurotransmitters, transient tonic firing is observed, followed by the reappearance of a M-bM-^@M-^\sleep-likeM-bM-^@M-^] state. Besides electrophysiological similarities also the transcriptional profile of stimulated cortical cultures greatly resembles that of the cortex of sleep deprived animals. We then used our in vitro model to map the metabolic pathways activated by the M-bM-^@M-^\wake-likeM-bM-^@M-^] state and found evidence for increased lysolipid release, strongly suggesting that sleep plays a role in neuronal membrane homeostasis. With our in vitro model the cellular and molecular consequences of sleep loss and the genetic determinants of disturbed sleep can now be investigated in a dish. Keywords: stress response For the in vivo transcriptome analyses mice were sleep deprived for 6 hours and brain harvested immediately afterwards. For the in vitro analyses, cortical cultures were stimulated with a neurotransmitter cocktail and cells harvested 3 hours afterwards. Control mice were kept undisturbed in their home cage and control cultures were sham stimulated with water. Also, another set of sleep deprived mice as well as stimulated cultures were allowed to recover before being sampled the next day at the time of day at which sleep deprivation or stimulation started the day before).
2012-08-31 | E-GEOD-33491 | biostudies-arrayexpress
Project description:Why we sleep is still one of the most perplexing mysteries in biology. Strong evidence, however, indicates that sleep is necessary for normal brain function and that the need to sleep is a tightly regulated process. Surprisingly molecular mechanisms that determine the need to sleep are incompletely described. Moreover, very little is known about transcriptional changes that specifically accompany the accumulation and discharge of sleep need. In this study we present an integrated 2 cross-laboratory analysis of the effects of sleep deprivation (SD) in gene expression in the mouse cortex. We also evaluate changes in gene expression genome-wide following various lengths of subsequent recovery sleep. (RS). We demonstrate that changes in gene expression specifically linked to SD or RS, and not to technical factors (e.g. the assay used), requires a novel analysis methodology not previously utilized in the field of sleep research. Cortical samples from mice were analyzed, from groups that were sleep deprived, sleep deprived and allowed to recover for 1, 2, 3, or 6 hours, and circadian control animals that were not sleep deprived. The experimental protocol began at lights on (ZT0) with 13 mice: 1 sacrificed, 4 control mice left undisturbed, and 8 mice kept awake with gentle brushing when attempting to sleep. After 5 hours of sleep deprivation the mice were randomly assigned to recovery sleep or continued sleep deprivation, and at fixed intervals the mice were sacrificed, dissected and the left cortex retained. The experimental protocol was repeated 7 times, one animal per timepoint per experimental day, so that 7 independent experiments are represented for each timepoint. All animals were acclimated to the brushing and tapping on cages used during sleep deprivationfor 6 days, and dissections and tissue collection were performed by a single experimenter.
2016-09-07 | E-GEOD-78215 | biostudies-arrayexpress