MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease

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 express...

ver descrição completa

Detalhes bibliográficos
Autores: 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
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/173510
Acesso em linha:https://hdl.handle.net/2445/173510
Access Level:acceso abierto
Palavra-chave:Malalties per prions
Micro RNAs
Marcadors bioquímics
Prion diseases
MicroRNAs
Biochemical markers
id ES_20d586936a054c9b8fe2fe593798cd64
oai_identifier_str oai:diposit.ub.edu:2445/173510
network_acronym_str ES
network_name_str España
repository_id_str
spelling MicroRNA Alterations in a Tg501 Mouse Model of Prion DiseaseToivonen, Janne M.Sanz Rubio, DavidLópez Pérez, ÓscarMarín Moreno, AlbaBolea, RosaOsta, RosarioBadiola, Juan JoséZaragoza, PilarEspinosa, Juan CarlosTorres, Juan MariaMartín Burriel, InmaculadaMalalties per prionsMicro RNAsMarcadors bioquímicsPrion diseasesMicroRNAsBiochemical markersMicroRNAs (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.MDPI2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/173510Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3390/biom10060908Biomolecules, 2020, vol. 10, num. 6https://doi.org/10.3390/biom10060908cc by (c) Toivonen et al., 2020http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1735102026-05-27T06:46:51Z
dc.title.none.fl_str_mv MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease
title MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease
spellingShingle MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease
Toivonen, Janne M.
Malalties per prions
Micro RNAs
Marcadors bioquímics
Prion diseases
MicroRNAs
Biochemical markers
title_short MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease
title_full MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease
title_fullStr MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease
title_full_unstemmed MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease
title_sort MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease
dc.creator.none.fl_str_mv 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
author Toivonen, Janne M.
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malalties per prions
Micro RNAs
Marcadors bioquímics
Prion diseases
MicroRNAs
Biochemical markers
topic Malalties per prions
Micro RNAs
Marcadors bioquímics
Prion diseases
MicroRNAs
Biochemical markers
description 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.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/173510
url https://hdl.handle.net/2445/173510
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/biom10060908
Biomolecules, 2020, vol. 10, num. 6
https://doi.org/10.3390/biom10060908
dc.rights.none.fl_str_mv cc by (c) Toivonen et al., 2020
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Toivonen et al., 2020
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869404481756594176
score 15,223283

Registos relacionados