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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

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