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Genomewide effects of regular caffeine intake on hippocampal metabolism and learning-dependent transcription

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE167123 | GEO | 2022/06/22

REPOSITORIES: GEO

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Genomewide effects of regular caffeine intake on hippocampal metabolism and learning-dependent transcription [ChIP-Seq]

Project description:Caffeine is the most widely consumed psychoactive substance worldwide. Strikingly, molecular pathways engaged by its regular consumption remain unclear. We herein addressed the mechanisms associated with habitual (chronic) caffeine consumption in the mouse hippocampus using untargeted orthogonal-omics techniques. Our results revealed that caffeine exerts concerted pleiotropic effects in the hippocampus, at the epigenomic, proteomic and metabolomic levels, aimed at lowering metabolic-related processes while re-setting learning-associated transcriptome associated with neuronal activity. These processes involve BDNF, CREB and adenosine A2A receptors-related mechanisms. Altogether, these findings suggest that regular intake of caffeine improves the signal-to-noise ratio during information encoding in learning and bolsters the salience of information encoding in brain circuits.

2022-06-22 | GSE167122 | GEO

Genomewide effects of regular caffeine intake on hippocampal metabolism and learning-dependent transcription [RNA-Seq]

2022-06-22 | GSE167121 | GEO

Genomewide effects of regular caffeine intake on hippocampal metabolism and learning-dependent transcription [Cut & Tag]

Project description:Caffeine is the most widely consumed psychoactive substance worldwide. Strikingly, molecular pathways engaged by its regular consumption remain unclear. We herein addressed the mechanisms associated with habitual (chronic) caffeine consumption in the mouse hippocampus using untargeted orthogonal-omics techniques. Our results revealed that chronic caffeine exerts concerted pleiotropic effects in the hippocampus, at the epigenomic, proteomic and metabolomic levels, lowered metabolic-related processes in bulk tissue, while inducing neuronal-specific epigenetic changes at synaptic transmission/neuronal activity-related genes. Altogether, these findings suggest that regular intake of caffeine improves the signal-to-noise ratio during information encoding in learning in part through a re-setting of metabolic genes helping to bolster the salience of information processing in neuronal circuits.

2022-06-22 | GSE200156 | GEO

Genomewide effects of regular caffeine intake on hippocampal metabolism and learning-dependent transcription

Project description:Genomewide effects of regular caffeine intake on hippocampal metabolism and learning-dependent transcription

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Genomewide effects of regular caffeine intake on hippocampal metabolism and learning-dependent transcription [ChIP-Seq]

Project description:Genomewide effects of regular caffeine intake on hippocampal metabolism and learning-dependent transcription [ChIP-Seq]

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Genomewide effects of regular caffeine intake on hippocampal metabolism and learning-dependent transcription [RNA-Seq]

Project description:Genomewide effects of regular caffeine intake on hippocampal metabolism and learning-dependent transcription [RNA-Seq]

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Genomewide effects of regular caffeine intake on hippocampal metabolism and learning-dependent transcription [Cut & Tag]

Project description:Genomewide effects of regular caffeine intake on hippocampal metabolism and learning-dependent transcription [Cut & Tag]

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Cytochrome P450-dependent metabolism of caffeine in Drosophila melanogaster.

Project description:Caffeine (1, 3, 7-trimethylxanthine), an alkaloid produced by plants, has antioxidant and insecticide properties that can affect metabolism and cognition. In vertebrates, the metabolites derived from caffeine have been identified, and their functions have been characterized. However, the metabolites of caffeine in insects remain unknown. Thus, using radiolabelled caffeine, we have identified some of the primary caffeine metabolites produced in the body of Drosophila melanogaster males, including theobromine, paraxanthine and theophylline. In contrast to mammals, theobromine was the predominant metabolite (paraxanthine in humans; theophylline in monkeys; 1, 3, 7-trimethyluric acid in rodents). A transcriptomic screen of Drosophila flies exposed to caffeine revealed the coordinated variation of a large set of genes that encode xenobiotic-metabolizing proteins, including several cytochromes P450s (CYPs) that were highly overexpressed. Flies treated with metyrapone--an inhibitor of CYP enzymes--showed dramatically decreased caffeine metabolism, indicating that CYPs are involved in this process. Using interference RNA genetic silencing, we measured the metabolic and transcriptomic effect of three candidate CYPs. Silencing of CYP6d5 completely abolished theobromine synthesis, whereas CYP6a8 and CYP12d1 silencing induced different consequences on metabolism and gene expression. Therefore, we characterized several metabolic products and some enzymes potentially involved in the degradation of caffeine. In conclusion, this pioneer approach to caffeine metabolism in insects opens novel perspectives for the investigation of the physiological effects of caffeine metabolites. It also indicates that caffeine could be used as a biomarker to evaluate CYP phenotypes in Drosophila and other insects.

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Effects of caffeine intake and exercise intensity on executive and arousal vigilance.

Project description:During physical efforts and sport practice, vigilance is responsible for maintaining an optimal state of activation, guaranteeing the ability to quickly respond and detect unexpected, but critical, stimuli over time. Caffeine and physical exercise are able to modulate the activation state, affecting vigilance performance. The aim of the present work was to assess the specific effects and modulations of caffeine intake and two physical intensities on vigilance components. Participants performed an attentional task (ANTI-Vea) to measure the executive and arousal components of vigilance, in six double-blinded counterbalanced sessions combining caffeine, placebo, or no-ingestion, with light vs. moderate cyclergometer exercise. Exercise at moderate intensity improved executive vigilance with faster overall reaction time (RT), without impairing error rates. Instead, caffeine intake generally improved arousal vigilance. In conclusion, caffeine and acute exercise seems to moderate executive and arousal vigilance in different ways.

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Coffee intake, variants in genes involved in caffeine metabolism, and the risk of epithelial ovarian cancer.

Project description:We evaluated whether genetic variability, as well as menopausal status, modify the association between coffee intake and risk of ovarian cancer. Risk factor information and biologic specimens from three large epidemiological studies, the Nurses' Health Study (NHS), NHSII, and the New England based Case-Control Study of ovarian cancer (NECC) were pooled resulting in 1,354 ovarian cancer cases and 1,851 controls for analysis. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using conditional (NHS/NHSII) and unconditional (NECC) logistic regression. Coffee consumption was not associated with overall risk (OR = 0.99; 95% CI 0.77-1.28); however, there was a suggested increased risk of ovarian cancer among premenopausal women in the NECC only and an inverse association among postmenopausal women. Carrying one or both of the variant CYP19013 A or CYP19027 G alleles was associated with an 18% increased (P for trend = 0.02) and 15% decreased (P for trend = 0.05) risk of ovarian cancer, respectively. Variation in CYP1A1, CYP1A2, or CYP2A6 did not explain the inconsistent reports of coffee intake and risk. Furthermore, we did not observe any clear gene-environment interactions between caffeine metabolizing genes and ovarian cancer. Future studies evaluating mechanisms by which coffee mediates this relationship are warranted.

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