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doi:10.22028/D291-43557
Titel: | Distinct impacts of alpha-synuclein overexpression on the hippocampal epigenome of mice in standard and enriched environments |
VerfasserIn: | Schaffner, Samantha L. Wassouf, Zinah Hentrich, Thomas Nuesch-Germano, Melanie Kobor, Michael S. Schulze-Hentrich, Julia |
Sprache: | Englisch |
Titel: | Neurobiology of disease |
Bandnummer: | 186 |
Verlag/Plattform: | Elsevier |
Erscheinungsjahr: | 2023 |
Freie Schlagwörter: | Alpha-synuclein Epigenetics Multiomics integration Gene-environment interaction |
DDC-Sachgruppe: | 500 Naturwissenschaften |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | Elevated alpha-synuclein (SNCA) gene expression is associated with transcriptional deregulation and increased risk of Parkinson's disease, which may be partially ameliorated by environmental enrichment. At the molecular level, there is emerging evidence that excess alpha-synuclein protein (aSyn) impacts the epigenome through direct and/or indirect mechanisms. However, the extents to which the effects of both aSyn and the environment converge at the epigenome and whether epigenetic alterations underpin the preventive effects of environmental factors on transcription remain to be elucidated. Here, we profiled five DNA and histone modifications in the hippocampus of wild-type and transgenic mice overexpressing human SNCA. Mice of each genotype were housed under either standard conditions or in an enriched environment (EE) for 12 months. SNCA overexpression induced hippocampal CpG hydroxymethylation and histone H3K27 acetylation changes that associated with genotype more than environment. Excess aSyn was also associated with genotype- and environment-dependent changes in non-CpG (CpH) DNA methylation and H3K4 methylation. These H3K4 methylation changes included loci where the EE ameliorated the impacts of the transgene as well as loci resistant to the effects of environmental enrichment in transgenic mice. In addition, select H3K4 monomethylation alterations were associated with changes in mRNA expression. Our results suggested an environment-dependent impact of excess aSyn on some functionally relevant parts of the epigenome, and will ultimately enhance our understanding of the molecular etiology of Parkinson's disease and other synucleinopathies. |
DOI der Erstveröffentlichung: | 10.1016/j.nbd.2023.106274 |
URL der Erstveröffentlichung: | https://www.sciencedirect.com/science/article/pii/S0969996123002899 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-435572 hdl:20.500.11880/39028 http://dx.doi.org/10.22028/D291-43557 |
ISSN: | 1095-953X 0969-9961 |
Datum des Eintrags: | 26-Nov-2024 |
Fakultät: | NT - Naturwissenschaftlich- Technische Fakultät |
Fachrichtung: | NT - Biowissenschaften |
Professur: | NT - Prof. Dr. Julia Schulze-Hentrich |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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1-s2.0-S0969996123002899-main.pdf | 6,74 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons