125319 20241125101153.0 doi 10.3390/ijms24021621 sideral 132932 ART-2023-132932 eng Hernaiz, Adelaida Universidad de Zaragoza (orcid)0000-0002-6806-9990 5-Methylcytosine and 5-Hydroxymethylcytosine in scrapie-infected sheep and mouse brain tissues 2023 Access copy available to the general public Unrestricted Scrapie is a neurodegenerative disorder belonging to the group of transmissible spongiform encephalopathies or prion diseases, which are caused by an infectious isoform of the innocuous cellular prion protein (PrPC) known as PrPSc. DNA methylation, one of the most studied epigenetic mechanisms, is essential for the proper functioning of the central nervous system. Recent findings point to possible involvement of DNA methylation in the pathogenesis of prion diseases, but there is still a lack of knowledge about the behavior of this epigenetic mechanism in such neurodegenerative disorders. Here, we evaluated by immunohistochemistry the 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels in sheep and mouse brain tissues infected with scrapie. Expression analysis of different gene coding for epigenetic regulatory enzymes (DNMT1, DNMT3A, DNMT3B, HDAC1, HDAC2, TET1, and TET2) was also carried out. A decrease in 5mC levels was observed in scrapie-affected sheep and mice compared to healthy animals, whereas 5hmC displayed opposite patterns between the two models, demonstrating a decrease in 5hmC in scrapie-infected sheep and an increase in preclinical mice. 5mC correlated with prion-related lesions in mice and sheep, but 5hmC was associated with prion lesions only in sheep. Differences in the expression changes of epigenetic regulatory genes were found between both disease models, being differentially expressed Dnmt3b, Hdac1, and Tet1 in mice and HDAC2 in sheep. Our results support the evidence that DNA methylation in both forms, 5mC and 5hmC, and its associated epigenetic enzymes, take part in the neurodegenerative course of prion diseases. info:eu-repo/grantAgreement/ES/DGA-FSE/IIU-2023-2017 info:eu-repo/grantAgreement/ES/DGA/19-20R-LAGENBIO-GROUP info:eu-repo/grantAgreement/ES/MINECO/AGL2015-67945-P info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.9 2023 BIOCHEMISTRY & MOLECULAR BIOLOGY 66 / 313 = 0.211 2023 Q1 T1 CHEMISTRY, MULTIDISCIPLINARY 68 / 231 = 0.294 2023 Q2 T1 1.179 2023 Medicine (miscellaneous) 2023 Q1 Physical and Theoretical Chemistry 2023 Q1 Computer Science Applications 2023 Q1 Inorganic Chemistry 2023 Q1 Spectroscopy 2023 Q1 Organic Chemistry 2023 Q1 Molecular Biology 2023 Q2 Catalysis 2023 Q2 8.1 2023 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Sentre, Sara Betancor, Marina Universidad de Zaragoza (orcid)0000-0002-0388-9429 López Pérez, Óscar Salinas Pena, Mónica Zaragoza, Pilar Universidad de Zaragoza (orcid)0000-0001-5740-0185 Badiola, Juan José Universidad de Zaragoza (orcid)0000-0002-7173-7216 Toivonen, Janne Markus Universidad de Zaragoza (orcid)0000-0002-7243-1737 Bolea, Rosa Universidad de Zaragoza (orcid)0000-0002-2746-3932 Martín Burriel, Inmaculada Universidad de Zaragoza (orcid)0000-0001-6016-4726 1001 420 Universidad de Zaragoza Dpto. Anatom.,Embri.Genét.Ani. Área Genética 1009 773 Universidad de Zaragoza Dpto. Patología Animal Área Sanidad Animal 24, 2 (2023), 1621 [21 pp] Int. j. mol. sci. International Journal of Molecular Sciences 1661-6596 8230010 http://zaguan.unizar.es/record/125319/files/texto_completo.pdf Versión publicada 2784582 http://zaguan.unizar.es/record/125319/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:125319 articulos driver 2024-11-22-12:07:58 ARTICLE