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| Verfasst von: | Zillich, Eric [VerfasserIn]  |
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| | Belschner, Hanna [VerfasserIn] |
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| | Avetyan, Diana [VerfasserIn] |
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| | Andrade-Brito, Diego E. [VerfasserIn] |
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| | Martínez-Magaña, José Jaime [VerfasserIn] |
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| | Frank, Josef [VerfasserIn] |
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| | Mechawar, Naguib [VerfasserIn] |
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| | Turecki, Gustavo [VerfasserIn] |
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| | Cabana-Domínguez, Judit [VerfasserIn] |
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| | Fernàndez-Castillo, Noèlia [VerfasserIn] |
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| | Cormand, Bru [VerfasserIn] |
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| | Montalvo-Ortiz, Janitza L. [VerfasserIn] |
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| | Nöthen, Markus M. [VerfasserIn] |
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| | Hansson, Anita C. [VerfasserIn] |
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| | Rietschel, Marcella [VerfasserIn] |
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| | Spanagel, Rainer [VerfasserIn] |
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| | Witt, Stephanie [VerfasserIn] |
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| | Zillich, Lea [VerfasserIn] |
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| Titel: | Multi-omics profiling of DNA methylation and gene expression alterations in human cocaine use disorder |
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| Verf.angabe: | Eric Zillich, Hanna Belschner, Diana Avetyan, Diego Andrade-Brito, José Jaime Martínez-Magaña, Josef Frank, Naguib Mechawar, Gustavo Turecki, Judit Cabana-Domínguez, Noèlia Fernàndez-Castillo, Bru Cormand, Janitza L. Montalvo-Ortiz, Markus M. Nöthen, Anita C. Hansson, Marcella Rietschel, Rainer Spanagel, Stephanie H. Witt and Lea Zillich |
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| E-Jahr: | 2024 |
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| Jahr: | 09 October 2024 |
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| Umfang: | 14 S. |
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| Illustrationen: | Illustrationen |
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| Fussnoten: | Gesehen am 24.03.2025 |
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| Titel Quelle: | Enthalten in: Translational Psychiatry |
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| Ort Quelle: | London : Nature Publishing Group, 2011 |
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| Jahr Quelle: | 2024 |
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| Band/Heft Quelle: | 14(2024), 1, Seite 1-14 |
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| ISSN Quelle: | 2158-3188 |
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| Abstract: | Structural and functional changes of the brain are assumed to contribute to excessive cocaine intake, craving, and relapse in cocaine use disorder (CUD). Epigenetic and transcriptional changes were hypothesized as a molecular basis for CUD-associated brain alterations. Here we performed a multi-omics study of CUD by integrating epigenome-wide methylomic (N = 42) and transcriptomic (N = 25) data from the same individuals using postmortem brain tissue of Brodmann Area 9 (BA9). Of the N = 1 057 differentially expressed genes (p < 0.05), one gene, ZFAND2A, was significantly upregulated in CUD at transcriptome-wide significance (q < 0.05). Differential alternative splicing (AS) analysis revealed N = 98 alternatively spliced transcripts enriched in axon and dendrite extension pathways. Strong convergent overlap in CUD-associated expression deregulation was found between our BA9 cohort and independent replication datasets. Epigenomic, transcriptomic, and AS changes in BA9 converged at two genes, ZBTB4 and INPP5E. In pathway analyses, synaptic signaling, neuron morphogenesis, and fatty acid metabolism emerged as the most prominently deregulated biological processes. Drug repositioning analysis revealed glucocorticoid receptor targeting drugs as most potent in reversing the CUD expression profile. Our study highlights the value of multi-omics approaches for an in-depth molecular characterization and provides insights into the relationship between CUD-associated epigenomic and transcriptomic signatures in the human prefrontal cortex. |
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| DOI: | doi:10.1038/s41398-024-03139-9 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Volltext: https://doi.org/10.1038/s41398-024-03139-9 |
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| | kostenfrei: Volltext: https://www.nature.com/articles/s41398-024-03139-9 |
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| | DOI: https://doi.org/10.1038/s41398-024-03139-9 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Addiction |
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| | Epigenetics and plasticity |
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| K10plus-PPN: | 1920384839 |
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| Verknüpfungen: | → Zeitschrift |
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Multi-omics profiling of DNA methylation and gene expression alterations in human cocaine use disorder / Zillich, Eric [VerfasserIn]; 09 October 2024 (Online-Ressource)
