000112390 001__ 112390 000112390 005__ 20240319080947.0 000112390 0247_ $$2doi$$a10.3389/fvets.2022.824677 000112390 0248_ $$2sideral$$a128291 000112390 037__ $$aART-2022-128291 000112390 041__ $$aeng 000112390 100__ $$0(orcid)0000-0002-6806-9990$$aHernaiz Martorell, A.$$uUniversidad de Zaragoza 000112390 245__ $$aGenome-Wide Methylation Profiling in the Thalamus of Scrapie Sheep 000112390 260__ $$c2022 000112390 5060_ $$aAccess copy available to the general public$$fUnrestricted 000112390 5203_ $$aScrapie is a neurodegenerative disorder belonging to the group of transmissible spongiform encephalopathy (TSE). Scrapie occurs in sheep and goats, which are considered good natural animal models of these TSE. Changes in DNA methylation occur in the central nervous system (CNS) of patients suffering from prion-like neurodegenerative diseases, such as Alzheimer''s disease. Nevertheless, potential DNA methylation alterations have not yet been investigated in the CNS of any prion disease model or naturally infected cases, neither in humans nor in animals. Genome-wide DNA methylation patterns were studied in the thalamus obtained from sheep naturally infected with scrapie at a clinical stage (n = 4) and from controls (n = 4) by performing a whole-genome bisulfite sequencing (WGBS) analysis. Ewes carried the scrapie-susceptible ARQ/ARQ PRNP genotype and were sacrificed at a similar age (4–6 years). Although the average genomic methylation levels were similar between the control and the scrapie animals, we identified 8, 907 significant differentially methylated regions (DMRs) and 39 promoters (DMPs). Gene Ontology analysis revealed that hypomethylated DMRs were enriched in genes involved in transmembrane transport and cell adhesion, whereas hypermethylated DMRs were related to intracellular signal transduction genes. Moreover, genes highly expressed in specific types of CNS cells and those previously described to be differentially expressed in scrapie brains contained DMRs. Finally, a quantitative PCR (qPCR) validation indicated differences in the expression of five genes (PCDH19, SNCG, WDR45B, PEX1, and CABIN1) that matched the methylation changes observed in the genomic study. Altogether, these results suggest a potential regulatory role of DNA methylation in prion neuropathology. Copyright © 2022 Hernaiz, Sanz, Sentre, Ranera, Lopez-Pérez, Zaragoza, Badiola, Filali, Bolea, Toivonen and Martín-Burriel. 000112390 536__ $$9info:eu-repo/grantAgreement/ES/DGA/C012-2014$$9info:eu-repo/grantAgreement/ES/DGA-FSE/IIU-2023-2017$$9info:eu-repo/grantAgreement/ES/MICINN/RTI2018-098711-B-I00$$9info:eu-repo/grantAgreement/ES/MINECO/AGL2015-67945-P 000112390 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000112390 590__ $$a3.2$$b2022 000112390 592__ $$a0.737$$b2022 000112390 591__ $$aVETERINARY SCIENCES$$b12 / 144 = 0.083$$c2022$$dQ1$$eT1 000112390 593__ $$aVeterinary (miscellaneous)$$c2022$$dQ1 000112390 594__ $$a3.8$$b2022 000112390 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000112390 700__ $$0(orcid)0000-0001-6489-8399$$aSanz Fernández, A.$$uUniversidad de Zaragoza 000112390 700__ $$aSentre, S. 000112390 700__ $$aRanera, B. 000112390 700__ $$0(orcid)0000-0003-2454-2114$$aLopez-Pérez, O. 000112390 700__ $$0(orcid)0000-0001-5740-0185$$aZaragoza Fernández, P.$$uUniversidad de Zaragoza 000112390 700__ $$0(orcid)0000-0002-7173-7216$$aBadiola Díez, J.J.$$uUniversidad de Zaragoza 000112390 700__ $$0(orcid)0000-0003-3352-740X$$aFilali, H. 000112390 700__ $$0(orcid)0000-0002-2746-3932$$aBolea Bailo, R.$$uUniversidad de Zaragoza 000112390 700__ $$0(orcid)0000-0002-7243-1737$$aToivonen, J.M$$uUniversidad de Zaragoza 000112390 700__ $$0(orcid)0000-0001-6016-4726$$aMartín-Burriel, I.$$uUniversidad de Zaragoza 000112390 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética 000112390 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal 000112390 773__ $$g9 (2022), 824677 [16 pp.]$$pFront. vet. sci.$$tFrontiers in Veterinary Science$$x2297-1769 000112390 8564_ $$s2311290$$uhttps://zaguan.unizar.es/record/112390/files/texto_completo.pdf$$yVersión publicada 000112390 8564_ $$s2423876$$uhttps://zaguan.unizar.es/record/112390/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000112390 909CO $$ooai:zaguan.unizar.es:112390$$particulos$$pdriver 000112390 951__ $$a2024-03-18-12:43:29 000112390 980__ $$aARTICLE