000094559 001__ 94559 000094559 005__ 20240104111816.0 000094559 0247_ $$2doi$$a10.3390/biom10060908 000094559 0248_ $$2sideral$$a118634 000094559 037__ $$aART-2020-118634 000094559 041__ $$aeng 000094559 100__ $$0(orcid)0000-0002-7243-1737$$aToivonen, Janne M.$$uUniversidad de Zaragoza 000094559 245__ $$aMicroRNA Alterations in a Tg501 Mouse Model of Prion Disease 000094559 260__ $$c2020 000094559 5060_ $$aAccess copy available to the general public$$fUnrestricted 000094559 5203_ $$aMicroRNAs (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. 000094559 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/AGL2015-67945-P$$9info:eu-repo/grantAgreement/ES/MICINN/RTI2018-098711-B-I00$$9info:eu-repo/grantAgreement/EUR/INTERREG-POCTEFA/EFA-148-16 REDPRION$$9info:eu-repo/grantAgreement/ES/FIS/PI17-00949$$9info:eu-repo/grantAgreement/ES/DGA/A19-17R 000094559 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000094559 590__ $$a4.879$$b2020 000094559 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b96 / 296 = 0.324$$c2020$$dQ2$$eT1 000094559 592__ $$a1.125$$b2020 000094559 593__ $$aMolecular Biology$$c2020$$dQ2 000094559 593__ $$aBiochemistry$$c2020$$dQ2 000094559 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000094559 700__ $$0(orcid)0000-0002-5228-248X$$aSanz-Rubio, David 000094559 700__ $$0(orcid)0000-0003-2454-2114$$aLópez-Pérez, Óscar 000094559 700__ $$aMarín-Moreno, Alba 000094559 700__ $$0(orcid)0000-0002-2746-3932$$aBolea, Rosa$$uUniversidad de Zaragoza 000094559 700__ $$0(orcid)0000-0001-5687-6704$$aOsta, Rosario$$uUniversidad de Zaragoza 000094559 700__ $$0(orcid)0000-0002-7173-7216$$aBadiola, Juan J.$$uUniversidad de Zaragoza 000094559 700__ $$0(orcid)0000-0001-5740-0185$$aZaragoza, Pilar$$uUniversidad de Zaragoza 000094559 700__ $$aEspinosa, Juan Carlos 000094559 700__ $$aTorres, Juan María 000094559 700__ $$0(orcid)0000-0001-6016-4726$$aMartín-Burriel, Inmaculada$$uUniversidad de Zaragoza 000094559 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética 000094559 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal 000094559 773__ $$g10, 6 (2020), 908 [20 pp.]$$tBiomolecules$$x2218-273X 000094559 8564_ $$s8119954$$uhttps://zaguan.unizar.es/record/94559/files/texto_completo.pdf$$yVersión publicada 000094559 8564_ $$s483225$$uhttps://zaguan.unizar.es/record/94559/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000094559 909CO $$ooai:zaguan.unizar.es:94559$$particulos$$pdriver 000094559 951__ $$a2024-01-04-11:04:48 000094559 980__ $$aARTICLE