5-Methylcytosine and 5-Hydroxymethylcytosine in scrapie-infected sheep and mouse brain tissues

Hernaiz, Adelaida (Universidad de Zaragoza) ; Sentre, Sara ; Betancor, Marina (Universidad de Zaragoza) ; López Pérez, Óscar ; Salinas Pena, Mónica ; Zaragoza, Pilar (Universidad de Zaragoza) ; Badiola, Juan José (Universidad de Zaragoza) ; Toivonen, Janne Markus (Universidad de Zaragoza) ; Bolea, Rosa (Universidad de Zaragoza) ; Martín Burriel, Inmaculada (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.3390/ijms24021621

Año: 2023

Publicado en: International Journal of Molecular Sciences 24, 2 (2023), 1621 [21 pp]
ISSN: 1661-6596

Factor impacto JCR: 4.9 (2023)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 66 / 313 = 0.211 (2023) - Q1 - T1
Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 68 / 231 = 0.294 (2023) - Q2 - T1

Factor impacto CITESCORE: 8.1 - Spectroscopy (Q1) - Computer Science Applications (Q1) - Physical and Theoretical Chemistry (Q1) - Inorganic Chemistry (Q1) - Organic Chemistry (Q1) - Molecular Biology (Q2) - Catalysis (Q2)

Factor impacto SCIMAGO: 1.179 - Medicine (miscellaneous) (Q1) - Physical and Theoretical Chemistry (Q1) - Computer Science Applications (Q1) - Inorganic Chemistry (Q1) - Spectroscopy (Q1) - Organic Chemistry (Q1) - Molecular Biology (Q2) - Catalysis (Q2)

Financiación: info:eu-repo/grantAgreement/ES/DGA-FSE/IIU-2023-2017
Financiación: info:eu-repo/grantAgreement/ES/DGA/19-20R-LAGENBIO-GROUP
Financiación: info:eu-repo/grantAgreement/ES/MINECO/AGL2015-67945-P

Tipo y forma: Article (Published version)

Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.)
Área (Departamento): Área Sanidad Animal (Dpto. Patología Animal)