Diurnal gene expression profiles in mouse brain tissues constituting the central dopamine system
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ABSTRACT:
PROVIDER: PRJNA998378 | ENA |
REPOSITORIES: ENA
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Project description:The circadian regulation of gene expression underlies orchestrated daily rhythms in physiology, metabolism, and behavior. The central dopamine (DA) system arising from DA neurons in the ventral midbrain has been implicated in a wide range of brain functions. Growing evidence suggests that DA transmission follows daily oscillations at multiple regulatory steps, and its dysfunction is closely related to the onset of various neuropsychiatric diseases. We examined diurnal gene expression profiles across key brain areas constituting the central DA pathways in mice by use of microarray analyses to identify rhythmically expressed genes according to the time of day (TOD).
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Project description:Genes that establish the circadian clock have differential expression with respect to solar time in central and peripheral tissues. Here, we find circadian-time-induced differential expression in a large number of genes not associated with circadian rhythms in two brain regions lacking overt circadian function: the dorsal vagal complex (DVC) and the central nucleus of the amygdala (CeA). These regions primarily engage in autonomic, homeostatic, and emotional regulation. However, we find striking diurnal shifts in gene expression in these regions of male Sprague Dawley rats with no obvious patterns that could be attributed to function or region. These findings have implications for the design of gene expression studies as well as for the potential effects of xenobiotics on these regions that regulate autonomic and emotional states. Micropunches of dorsal vagal complex (DVC) and central nucleus of the amygdala (CeA) were collected from male, Sprague Dawley rats at three different times of the day. Animals were not experimentally different in any way except for the time of sacrifice and collction. Gene expression of 145 genes were measured with Fluidigm's Biomark 96.96 platform.
2020-03-27 | GSE147569 | GEO
Project description:The dopamine transporter facilitates dopamine reuptake from the extracellular space to terminate neurotransmission. The transporter belongs to the neurotransmitter:sodium symporter family, which includes transporters for serotonin, norepinephrine, and GABA that utilize the Na+ gradient to drive the uptake of substrate. Decades ago, it was shown that the serotonin transporter also antiports K+, but investigations of K+-coupled transport in other neurotransmitter:sodium symporters have been inconclusive. Here, we show that ligand binding to the drosophila- and human dopamine transporters are inhibited by K+, and the conformational dynamics of the drosophila dopamine transporter in K+ are divergent from the apo- and Na+-states. Furthermore, we found that K+ increased dopamine uptake by the drosophila dopamine transporter in liposomes, and visualized Na+ and K+ fluxes in single proteoliposomes using fluorescent ion indicators. Our results expand on the fundamentals of dopamine transport and prompt a reevaluation of the impact of K+ on other transporters in this pharmacologically important family.
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Project description:Spatio-temporal gene expression patterns underlie time-of-the day specific functional specialization of different organs. Although circadian gene expression atlases from model organisms including the nocturnal mouse are available, they are limited to a few peripheral organs. Here we report the circadian transcriptome of 64 different tissues, including 22 different brain regions, sampled every 2 h over 24 h, from the diurnal primate Papio Anubis. We found that the primate genome is vastly rhythmic with up to 67% of genes showing daily rhythms in expression. In addition to the diversity of transcripts in each tissue, the repertoire and phases of expression of cycling transcripts impart another layer of functional specialization to each tissue. Transcripts that are ubiquitously expressed and participate in essential cellular functions are more likely to exhibit rhythmic expression in a tissue-specific manner. At the whole organism level, the peak phases of rhythmic transcripts are largely clustered around dawn and dusk with a "quiescent period" during the first half of the night. Our findings also unveil a different temporal organization of central and peripheral tissues between diurnal and nocturnal animals. This study will contribute significantly to understanding circadian regulation of organs function and contribution of circadian rhythm disruption to diseases.
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Project description:Plant growth and survival depends to a large extent on the diurnal regulation of cellular processes. Although extensively studied at the transcript level, notably less is known about diurnal fluctuations at the protein level. Here, we report a high-resolution quantitative time-course of the Arabidopsis rosette proteome and phosphoproteome over a 12 h light:12 h dark diel cycle. We monitored the proteome every 2 h and the phosphoproteome immediately before and after the light-to-dark and dark-to-light transitions. Notably, we quantified nearly 5000 proteins and 1800 phosphopeptides, of which 288 and 225, respectively, were found to fluctuate over the time-course. Diurnal proteome and phosphoproteome changes were related to diverse biological processes, including protein translation, light detection, photosynthesis, metabolism and transport. Together, these datasets represent the most comprehensive proteomic analysis of Arabidopsis rosettes to date, allowing us to make multi-level inferences about the diurnal regulation of key cellular plant processes plants.
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Project description:Substance use disorders (SUDs) are associated with disruptions in sleep and circadian rhythms that persist during abstinence and may contribute to relapse risk. Repeated use of substances such as psychostimulants and opioids may lead to significant alterations in molecular rhythms in the nucleus accumbens (NAc), a brain region central to reward and motivation. Previous studies have identified rhythm alterations in the transcriptome of the NAc and other brain regions following the administration of psychostimulants or opioids. However, little is known about the impact of substance use on the diurnal rhythms of the proteome in the NAc. We used liquid chromatography coupled to tandem mass spectrometry-based (LC-MS/MS) quantitative proteomics, along with a data-independent acquisition (DIA) analysis pipeline, to investigate the effects of cocaine or morphine administration on diurnal rhythms of proteome in the mouse NAc. Overall, our data reveals cocaine and morphine differentially alters diurnal rhythms of the proteome in the NAc, with largely independent differentially expressed proteins dependent on time-of-day. Pathways enriched from cocaine altered protein rhythms were primarily associated with glucocorticoid signaling and metabolism, whereas morphine was associated with neuroinflammation. Collectively, these findings are the first to characterize the diurnal regulation of the NAc proteome and demonstrate a novel relationship between phase-dependent regulation of protein expression and the differential effects of cocaine and morphine on the NAc proteome.
2023-07-20 | PXD042043 | Pride
Project description:Most animals restrict their activity to specific part of the day, being either diurnal, nocturnal, or crepuscular. The genetic basis underlying this diurnal preference is largely unknown. Under laboratory conditions, Drosophila melanogaster is crepuscular, showing a bi-modal activity profile. However, recent experiments in our lab indicated that high variability among individuals exist, particularly in strains that derive from different wild populations. By assembling together flies from various geographical strains, we have generated a highly diverse population whose progeny exhibited extreme diurnal preference, including diurnal and nocturnal flies. We have used this population as a starting point for an artificial selection experiment in which we selected males that show the most extreme diurnal preference and mated them to their sisters. The response to selection was strong, and already after 10 selection cycles we obtained highly diurnal (D) and nocturnal (N) strains. Another strain that was not selected and showed intermediate behaviour (crepuscular) served as a control (C). These strains provide us with a unique opportunity to understand the genetics of diurnal preference.
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