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Spatiotemporal dysregulation of neuron-glia related genes and pro-/anti-inflammatory mirnas in the 5xFAD mouse model of Alzheimer’s diseaseouse model of Alzheimer’s disease

2024Journal article Open access
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dc.contributor.authorIanni, Marta
dc.contributor.authorCorraliza-Gomez, Miriam
dc.contributor.authorCosta-Coelho, Tiago
dc.contributor.authorFerreira-Manso, Mafalda
dc.contributor.authorInteiro-Oliveira, Sara
dc.contributor.authorAlemãn-Serrano, Nuno
dc.contributor.authorSebastião, Ana M
dc.contributor.authorGarcia, Gonçalo
dc.contributor.authorDiógenes, Maria José
dc.contributor.authorBrites, Dora
dc.date.accessioned2025-06-12T13:51:35Z
dc.date.available2025-06-12T13:51:35Z
dc.date.issued2024
dc.description© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).pt_PT
dc.description.abstractAlzheimer's disease (AD), the leading cause of dementia, is a multifactorial disease influenced by aging, genetics, and environmental factors. miRNAs are crucial regulators of gene expression and play significant roles in AD onset and progression. This exploratory study analyzed the expression levels of 28 genes and 5 miRNAs (miR-124-3p, miR-125b-5p, miR-21-5p, miR-146a-5p, and miR-155-5p) related to AD pathology and neuroimmune responses using RT-qPCR. Analyses were conducted in the prefrontal cortex (PFC) and the hippocampus (HPC) of the 5xFAD mouse AD model at 6 and 9 months old. Data highlighted upregulated genes encoding for glial fibrillary acidic protein (Gfap), triggering receptor expressed on myeloid cells (Trem2) and cystatin F (Cst7), in the 5xFAD mice at both regions and ages highlighting their roles as critical disease players and potential biomarkers. Overexpression of genes encoding for CCAAT enhancer-binding protein alpha (Cebpa) and myelin proteolipid protein (Plp) in the PFC, as well as for BCL2 apoptosis regulator (Bcl2) and purinergic receptor P2Y12 (P2yr12) in the HPC, together with upregulated microRNA(miR)-146a-5p in the PFC, prevailed in 9-month-old animals. miR-155 positively correlated with miR-146a and miR-21 in the PFC, and miR-125b positively correlated with miR-155, miR-21, while miR-146a in the HPC. Correlations between genes and miRNAs were dynamic, varying by genotype, region, and age, suggesting an intricate, disease-modulated interaction between miRNAs and target pathways. These findings contribute to our understanding of miRNAs as therapeutic targets for AD, given their multifaceted effects on neurons and glial cells.pt_PT
dc.description.sponsorshipThis research was funded by Fundação para a Ciência e Tecnologia (FCT)-PTDC/MED-NEU/2382/2021, LISBOA-01-0145-FEDER-031395 and La Caixa Foundation-Luzón Foundation (HR21-00931) to DB and in part by UIDB/04138/2020 and UIDP/04138/2020 to iMed.ULisboa; SCML (MB35-2021) and PRR-02/C05-i01/2022 to MJD; PRR-IMM/BII/12-2023 to S.I-O.; GAPIC/FMUL 20210028; FCT PD/BD/10594/2022 to T.C-C. and PD/BD/10313/2022 to M.F-M.; Margarita Salas postdoctoral grant from the Spanish Ministry of Universities funded by the European Union-Next Generation EU and University of Valladolid to MCG; Erasmus+ (Università degli Studi di Trieste) to MI; 5/2022/PTDC/MED-NEU/2382/2021 to GG.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationInt J Mol Sci. 2024 Aug 31;25(17):9475pt_PT
dc.identifier.doi10.3390/ijms25179475pt_PT
dc.identifier.eissn1422-0067
dc.identifier.issn1661-6596
dc.identifier.urihttp://hdl.handle.net/10400.5/101533
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationLISBOA-01-0145-FEDER-031395pt_PT
dc.relationMB35-2021pt_PT
dc.relationPRR-02/C05-i01/2022pt_PT
dc.relationPRR-IMM/BII/12-2023pt_PT
dc.relationPD/BD/10594/2022pt_PT
dc.relationPD/BD/10313/2022pt_PT
dc.relation.publisherversionhttps://www.mdpi.com/journal/ijmspt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subject5xFAD mouse modelpt_PT
dc.subjectAlzheimer’s diseasept_PT
dc.subjectHippocampuspt_PT
dc.subjectMicroRNAspt_PT
dc.subjectNeurodegenerationpt_PT
dc.subjectNeuroimmune genespt_PT
dc.subjectNeuroinflammationpt_PT
dc.subjectPrefrontal cortexpt_PT
dc.titleSpatiotemporal dysregulation of neuron-glia related genes and pro-/anti-inflammatory mirnas in the 5xFAD mouse model of Alzheimer’s diseaseouse model of Alzheimer’s diseasept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017%2F2018) - Financiamento Base/UIDB%2F04138%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017%2F2018) - Financiamento Programático/UIDP%2F04138%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Concurso de Projetos IC&DT em Todos os Domínios Científicos/PTDC%2FMED-NEU%2F2382%2F2021/PT
oaire.citation.issue17pt_PT
oaire.citation.titleInternational Journal of Molecular Sciencespt_PT
oaire.citation.volume25pt_PT
oaire.fundingStreamConcurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017/2018) - Financiamento Base
oaire.fundingStreamConcurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017/2018) - Financiamento Programático
oaire.fundingStreamConcurso de Projetos IC&DT em Todos os Domínios Científicos
person.familyNameIanni
person.familyNameCosta-Coelho
person.familyNameFerreira Manso
person.familyNamede Oliveira
person.familyNameAleman Serrano Patriarca Ramalho
person.familyNameSebastião
person.familyNameGarcia
person.familyNamede Oliveira Diógenes Nogueira
person.familyNameBrites
person.givenNameMarta
person.givenNameTiago
person.givenNameMafalda
person.givenNameSara Inteiro
person.givenNameNuno
person.givenNameAna M
person.givenNameGonçalo
person.givenNameMaria José
person.givenNameDora
person.identifier927187
person.identifier695914
person.identifierM-8293-2013
person.identifier.ciencia-idDA17-0693-7756
person.identifier.ciencia-id7119-01F6-7187
person.identifier.ciencia-idCC19-EEBF-6052
person.identifier.ciencia-id5317-77BF-0B70
person.identifier.ciencia-id0C1A-611B-76A6
person.identifier.ciencia-idF112-55E8-E37E
person.identifier.ciencia-idD31E-5043-D433
person.identifier.ciencia-id4B10-886B-DAFC
person.identifier.ciencia-id921C-9B98-2867
person.identifier.orcid0009-0008-0241-967X
person.identifier.orcid0000-0003-3097-6728
person.identifier.orcid0000-0001-5074-8154
person.identifier.orcid0000-0002-1604-656X
person.identifier.orcid0000-0003-2100-1240
person.identifier.orcid0000-0001-9030-6115
person.identifier.orcid0000-0001-5526-5362
person.identifier.orcid0000-0001-5486-6246
person.identifier.orcid0000-0002-3024-9777
person.identifier.scopus-author-id7004409879
person.identifier.scopus-author-id57190496766
person.identifier.scopus-author-id7004026610
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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