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Profiling microglia in a mouse model of Machado–Joseph disease

2022-01-23Journal article Open access
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dc.contributor.authorCampos, Ana Bela
dc.contributor.authorSilva, Sara Duarte
dc.contributor.authorFernandes, Bruno
dc.contributor.authorNeves, Sofia Pereira das
dc.contributor.authorMarques, Fernanda
dc.contributor.authorCastro, Andreia Teixeira
dc.contributor.authorCarvalho, Andreia Neves
dc.contributor.authorFernandes, Daniela Monteiro
dc.contributor.authorPortugal, Camila Cabral
dc.contributor.authorSocodato, Renato
dc.contributor.authorSummavielle, Teresa
dc.contributor.authorAmbrósio, António Francisco
dc.contributor.authorRelvas, João Bettencourt
dc.contributor.authorMaciel, Patrícia
dc.date.accessioned2024-03-05T12:54:29Z
dc.date.available2024-03-05T12:54:29Z
dc.date.issued2022-01-23
dc.description.abstractMicroglia have been increasingly implicated in neurodegenerative diseases (NDs), and specific disease associated microglia (DAM) profiles have been defined for several of these NDs. Yet, the microglial profile in Machado–Joseph disease (MJD) remains unexplored. Here, we characterized the profile of microglia in the CMVMJD135 mouse model of MJD. This characterization was performed using primary microglial cultures and microglial cells obtained from disease-relevant brain regions of neonatal and adult CMVMJD135 mice, respectively. Machine learning models were implemented to identify potential clusters of microglia based on their morphological features, and an RNA-sequencing analysis was performed to identify molecular perturbations and potential therapeutic targets. Our findings reveal morphological alterations that point to an increased activation state of microglia in CMVMJD135 mice and a disease-specific transcriptional profile of MJD microglia, encompassing a total of 101 differentially expressed genes, with enrichment in molecular pathways related to oxidative stress, immune response, cell proliferation, cell death, and lipid metabolism. Overall, these results allowed us to define the cellular and molecular profile of MJD-associated microglia and to identify genes and pathways that might represent potential therapeutic targets for this disorder.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCampos, A. B., Duarte-Silva, S., Fernandes, B., das Neves, S. P., Marques, F., Teixeira-Castro, A., Neves-Carvalho, A., Monteiro-Fernandes, D., Portugal, C. C., Socodato, R., Summavielle, T., Ambrósio, A. F., Relvas, J. B., & Maciel, P. (2022). Profiling Microglia in a Mouse Model of Machado–Joseph Disease. Biomedicines, 10(2), Artigo 2. https://doi.org/10.3390/biomedicines10020237pt_PT
dc.identifier.doi10.3390/biomedicines10020237pt_PT
dc.identifier.eissn2227-9059
dc.identifier.urihttp://hdl.handle.net/10400.22/25124
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationPTDC/NEU-NMC/3648/2014pt_PT
dc.relationPOCI-01-0145-FEDER-016818pt_PT
dc.relationPTDC/MED-OUT/31987/2017pt_PT
dc.relationPD/BD/ 127828/2016pt_PT
dc.relationPTDC/MED-NEU/31318/2017pt_PT
dc.relationPPBI-POCI-01-0145-FEDER-022122pt_PT
dc.relationUIDB/50026/2020pt_PT
dc.relationUIDP/50026/202pt_PT
dc.relation.publisherversionhttps://www.mdpi.com/2227-9059/10/2/237pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectMicroglia Machado–Joseph diseasept_PT
dc.subjectCell morphologypt_PT
dc.subjectRNA-sequencingpt_PT
dc.subjectMachine learningpt_PT
dc.titleProfiling microglia in a mouse model of Machado–Joseph diseasept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage27pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleBiomedicinespt_PT
oaire.citation.volume10(2)pt_PT
person.familyNameSummavielle
person.givenNameTeresa
person.identifier677706
person.identifier.ciencia-idC41E-0816-5C85
person.identifier.orcid0000-0003-2548-6281
person.identifier.ridC-9776-2012
person.identifier.scopus-author-id6603092949
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication207ee2de-85a0-4144-9e7e-b376c600e065
relation.isAuthorOfPublication.latestForDiscovery207ee2de-85a0-4144-9e7e-b376c600e065

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