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http://hdl.handle.net/2445/173510
Title: | MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease |
Author: | Toivonen, Janne M. Sanz Rubio, David López Pérez, Óscar Marín Moreno, Alba Bolea, Rosa Osta, Rosario Badiola, Juan José Zaragoza, Pilar Espinosa, Juan Carlos Torres, Juan Maria Martín Burriel, Inmaculada |
Keywords: | Malalties per prions Micro RNAs Marcadors bioquímics Prion diseases MicroRNAs Biochemical markers |
Issue Date: | 1-Jun-2020 |
Publisher: | MDPI |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/biom10060908 |
It is part of: | Biomolecules, 2020, vol. 10, num. 6 |
URI: | http://hdl.handle.net/2445/173510 |
Related resource: | https://doi.org/10.3390/biom10060908 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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