000125319 001__ 125319
000125319 005__ 20240104111825.0
000125319 0247_ $$2doi$$a10.3390/ijms24021621
000125319 0248_ $$2sideral$$a132932
000125319 037__ $$aART-2023-132932
000125319 041__ $$aeng
000125319 100__ $$0(orcid)0000-0002-6806-9990$$aHernaiz, Adelaida$$uUniversidad de Zaragoza
000125319 245__ $$a5-Methylcytosine and 5-Hydroxymethylcytosine in scrapie-infected sheep and mouse brain tissues
000125319 260__ $$c2023
000125319 5060_ $$aAccess copy available to the general public$$fUnrestricted
000125319 5203_ $$aScrapie 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.
000125319 536__ $$9info:eu-repo/grantAgreement/ES/DGA-FSE/IIU-2023-2017$$9info:eu-repo/grantAgreement/ES/DGA/19-20R-LAGENBIO-GROUP$$9info:eu-repo/grantAgreement/ES/MINECO/AGL2015-67945-P
000125319 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000125319 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000125319 700__ $$aSentre, Sara
000125319 700__ $$0(orcid)0000-0002-0388-9429$$aBetancor, Marina$$uUniversidad de Zaragoza
000125319 700__ $$aLópez Pérez, Óscar
000125319 700__ $$aSalinas Pena, Mónica
000125319 700__ $$0(orcid)0000-0001-5740-0185$$aZaragoza, Pilar$$uUniversidad de Zaragoza
000125319 700__ $$0(orcid)0000-0002-7173-7216$$aBadiola, Juan José$$uUniversidad de Zaragoza
000125319 700__ $$0(orcid)0000-0002-7243-1737$$aToivonen, Janne Markus$$uUniversidad de Zaragoza
000125319 700__ $$0(orcid)0000-0002-2746-3932$$aBolea, Rosa$$uUniversidad de Zaragoza
000125319 700__ $$0(orcid)0000-0001-6016-4726$$aMartín Burriel, Inmaculada$$uUniversidad de Zaragoza
000125319 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética
000125319 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal
000125319 773__ $$g24, 2 (2023), 1621 [21 pp]$$pInt. j. mol. sci.$$tInternational Journal of Molecular Sciences$$x1661-6596
000125319 8564_ $$s8230010$$uhttps://zaguan.unizar.es/record/125319/files/texto_completo.pdf$$yVersión publicada
000125319 8564_ $$s2784582$$uhttps://zaguan.unizar.es/record/125319/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000125319 909CO $$ooai:zaguan.unizar.es:125319$$particulos$$pdriver
000125319 951__ $$a2024-01-04-11:10:33
000125319 980__ $$aARTICLE