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BAMBI and CHGA in Prion Diseases: Neuropathological Assessment and Potential Role as Disease Biomarkers
Open AccessArticle

MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease

1
Laboratorio de Genética Bioquímica (LAGENBIO), Facultad de Veterinaria, University of Zaragoza, 50013 Zaragoza, Spain
2
Instituto de Investigación Sanitaria Aragón (IIS Aragón), University of Zaragoza, 50009 Zaragoza, Spain
3
Instituto Agroalimentario de Aragón (IA2) University of Zaragoza-CITA, 50013 Zaragoza, Spain
4
The Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Institute Carlos III, 28031 Madrid, Spain
5
Centro de Encefalopatías y Enfermedades Transmisibles Emergentes, University of Zaragoza, 50013 Zaragoza, Spain
6
Instituto de Investigación Biomédica de Bellvitge (IDIBELL), 08908 Barcelona, Spain
7
Centro de Investigación en Sanidad Animal (CISA-INIA), 28130 Madrid, Spain
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(6), 908; https://doi.org/10.3390/biom10060908
Received: 30 April 2020 / Revised: 31 May 2020 / Accepted: 12 June 2020 / Published: 15 June 2020
(This article belongs to the Special Issue Prion Disease Biomarkers: Recent Advances)
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. View Full-Text
Keywords: prion diseases; scrapie; microRNA; biomarkers prion diseases; scrapie; microRNA; biomarkers
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Toivonen, J.M.; Sanz-Rubio, D.; López-Pérez, Ó.; Marín-Moreno, A.; Bolea, R.; Osta, R.; Badiola, J.J.; Zaragoza, P.; Espinosa, J.-C.; Torres, J.-M.; Martín-Burriel, I. MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease. Biomolecules 2020, 10, 908.

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