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MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease.
Biomolecules. 2020 06 15; 10(6)B

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.

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Authors+Show Affiliations

Toivonen JM
Laboratorio de Genética Bioquímica (LAGENBIO), Facultad de Veterinaria, University of Zaragoza, 50013 Zaragoza, Spain. Instituto de Investigación Sanitaria Aragón (IIS Aragón), University of Zaragoza, 50009 Zaragoza, Spain. Instituto Agroalimentario de Aragón (IA2) University of Zaragoza-CITA, 50013 Zaragoza, Spain. The Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Institute Carlos III, 28031 Madrid, Spain.
Sanz-Rubio D
Laboratorio de Genética Bioquímica (LAGENBIO), Facultad de Veterinaria, University of Zaragoza, 50013 Zaragoza, Spain. Instituto de Investigación Sanitaria Aragón (IIS Aragón), University of Zaragoza, 50009 Zaragoza, Spain.
López-Pérez Ó
Laboratorio de Genética Bioquímica (LAGENBIO), Facultad de Veterinaria, University of Zaragoza, 50013 Zaragoza, Spain. Instituto de Investigación Sanitaria Aragón (IIS Aragón), University of Zaragoza, 50009 Zaragoza, Spain. Instituto Agroalimentario de Aragón (IA2) University of Zaragoza-CITA, 50013 Zaragoza, Spain. The Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Institute Carlos III, 28031 Madrid, Spain. Centro de Encefalopatías y Enfermedades Transmisibles Emergentes, University of Zaragoza, 50013 Zaragoza, Spain. Instituto de Investigación Biomédica de Bellvitge (IDIBELL), 08908 Barcelona, Spain.
Marín-Moreno A
Centro de Investigación en Sanidad Animal (CISA-INIA), 28130 Madrid, Spain.
Bolea R
Instituto de Investigación Sanitaria Aragón (IIS Aragón), University of Zaragoza, 50009 Zaragoza, Spain. Instituto Agroalimentario de Aragón (IA2) University of Zaragoza-CITA, 50013 Zaragoza, Spain. Centro de Encefalopatías y Enfermedades Transmisibles Emergentes, University of Zaragoza, 50013 Zaragoza, Spain.
Osta R
Laboratorio de Genética Bioquímica (LAGENBIO), Facultad de Veterinaria, University of Zaragoza, 50013 Zaragoza, Spain. Instituto de Investigación Sanitaria Aragón (IIS Aragón), University of Zaragoza, 50009 Zaragoza, Spain. Instituto Agroalimentario de Aragón (IA2) University of Zaragoza-CITA, 50013 Zaragoza, Spain. The Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Institute Carlos III, 28031 Madrid, Spain.
Badiola JJ
Instituto de Investigación Sanitaria Aragón (IIS Aragón), University of Zaragoza, 50009 Zaragoza, Spain. Instituto Agroalimentario de Aragón (IA2) University of Zaragoza-CITA, 50013 Zaragoza, Spain. Centro de Encefalopatías y Enfermedades Transmisibles Emergentes, University of Zaragoza, 50013 Zaragoza, Spain.
Zaragoza P
Laboratorio de Genética Bioquímica (LAGENBIO), Facultad de Veterinaria, University of Zaragoza, 50013 Zaragoza, Spain. Instituto de Investigación Sanitaria Aragón (IIS Aragón), University of Zaragoza, 50009 Zaragoza, Spain. Instituto Agroalimentario de Aragón (IA2) University of Zaragoza-CITA, 50013 Zaragoza, Spain. The Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Institute Carlos III, 28031 Madrid, Spain.
Espinosa JC
Centro de Investigación en Sanidad Animal (CISA-INIA), 28130 Madrid, Spain.
Torres JM
Centro de Investigación en Sanidad Animal (CISA-INIA), 28130 Madrid, Spain.
Martín-Burriel I
Laboratorio de Genética Bioquímica (LAGENBIO), Facultad de Veterinaria, University of Zaragoza, 50013 Zaragoza, Spain. Instituto de Investigación Sanitaria Aragón (IIS Aragón), University of Zaragoza, 50009 Zaragoza, Spain. Instituto Agroalimentario de Aragón (IA2) University of Zaragoza-CITA, 50013 Zaragoza, Spain. The Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Institute Carlos III, 28031 Madrid, Spain. Centro de Encefalopatías y Enfermedades Transmisibles Emergentes, University of Zaragoza, 50013 Zaragoza, Spain.

MeSH

AnimalsDisease Models, AnimalGene Expression ProfilingGene Expression RegulationGene Regulatory NetworksGoat DiseasesGoatsMiceMice, TransgenicMicroRNAsPrion DiseasesSequence Analysis, RNA

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32549330

Citation

Toivonen, Janne M., et al. "MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease." Biomolecules, vol. 10, no. 6, 2020.
Toivonen JM, Sanz-Rubio D, López-Pérez Ó, et al. MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease. Biomolecules. 2020;10(6).
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. (2020). MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease. Biomolecules, 10(6). https://doi.org/10.3390/biom10060908
Toivonen JM, et al. MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease. Biomolecules. 2020 06 15;10(6) PubMed PMID: 32549330.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease. AU - Toivonen,Janne M, AU - Sanz-Rubio,David, AU - López-Pérez,Óscar, AU - Marín-Moreno,Alba, AU - Bolea,Rosa, AU - Osta,Rosario, AU - Badiola,Juan J, AU - Zaragoza,Pilar, AU - Espinosa,Juan-Carlos, AU - Torres,Juan-Maria, AU - Martín-Burriel,Inmaculada, Y1 - 2020/06/15/ PY - 2020/04/30/received PY - 2020/05/31/revised PY - 2020/06/12/accepted PY - 2020/6/19/entrez PY - 2020/6/19/pubmed PY - 2021/4/2/medline KW - biomarkers KW - microRNA KW - prion diseases KW - scrapie JF - Biomolecules JO - Biomolecules VL - 10 IS - 6 N2 - 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. SN - 2218-273X UR - https://www.unboundmedicine.com/medline/citation/32549330/MicroRNA_Alterations_in_a_Tg501_Mouse_Model_of_Prion_Disease_ DB - PRIME DP - Unbound Medicine ER -