94559 20240104111816.0 doi 10.3390/biom10060908 sideral 118634 ART-2020-118634 eng Toivonen, Janne M. Universidad de Zaragoza (orcid)0000-0002-7243-1737 MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease 2020 Access copy available to the general public Unrestricted MicroRNAs (miRNAs) may contribute to the development and pathology of many neurodegenerative diseases, including prion diseases. They are also promising biomarker candidates due to their stability in body fluids. We investigated miRNA alterations in a Tg501 mouse model of prion diseases that expresses a transgene encoding the goat prion protein (PRNP). Tg501 mice intracranially inoculated with mouse-adapted goat scrapie were compared with age-matched, mock inoculated controls in preclinical and clinical stages. Small RNA sequencing from the cervical spinal cord indicated that miR-223-3p, miR-151-3p, and miR-144-5p were dysregulated in scrapie-inoculated animals before the onset of symptoms. In clinical-stage animals, 23 significant miRNA alterations were found. These miRNAs were predicted to modify the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways including prion disease, extracellular matrix interactions, glutaminergic synapse, axon guidance, and transforming growth factor-beta signaling. MicroRNAs miR-146a-5p (up in cervical spinal cord) and miR-342-3p (down in cervical spinal cord, cerebellum and plasma), both indicated in neurodegenerative diseases earlier, were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Minimal changes observed before the disease onset suggests that most miRNA alterations observed here are driven by advanced prion-associated pathology, possibly limiting their use as diagnostic markers. However, the results encourage further mechanistic studies on miRNA-regulated pathways involved in these neurodegenerative conditions. info:eu-repo/grantAgreement/ES/DGA/A19-17R info:eu-repo/grantAgreement/ES/FIS/PI17-00949 info:eu-repo/grantAgreement/EUR/INTERREG-POCTEFA/EFA-148-16 REDPRION info:eu-repo/grantAgreement/ES/MICINN/RTI2018-098711-B-I00 info:eu-repo/grantAgreement/ES/MINECO/AGL2015-67945-P info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.879 2020 BIOCHEMISTRY & MOLECULAR BIOLOGY 96 / 296 = 0.324 2020 Q2 T1 1.125 2020 Molecular Biology 2020 Q2 Biochemistry 2020 Q2 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Sanz-Rubio, David (orcid)0000-0002-5228-248X López-Pérez, Óscar (orcid)0000-0003-2454-2114 Marín-Moreno, Alba Bolea, Rosa Universidad de Zaragoza (orcid)0000-0002-2746-3932 Osta, Rosario Universidad de Zaragoza (orcid)0000-0001-5687-6704 Badiola, Juan J. Universidad de Zaragoza (orcid)0000-0002-7173-7216 Zaragoza, Pilar Universidad de Zaragoza (orcid)0000-0001-5740-0185 Espinosa, Juan Carlos Torres, Juan María 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 10, 6 (2020), 908 [20 pp.] Biomolecules 2218-273X 8119954 http://zaguan.unizar.es/record/94559/files/texto_completo.pdf Versión publicada 483225 http://zaguan.unizar.es/record/94559/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:94559 articulos driver 2024-01-04-11:04:48 ARTICLE