Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/103216
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Fernandes, Adelaide | - |
dc.contributor.author | Caldeira, Cláudia | - |
dc.contributor.author | Cunha, Carolina | - |
dc.contributor.author | Ferreiro, Elisabete | - |
dc.contributor.author | Vaz, Ana Rita | - |
dc.contributor.author | Brites, Dora | - |
dc.date.accessioned | 2022-10-24T09:57:09Z | - |
dc.date.available | 2022-10-24T09:57:09Z | - |
dc.date.issued | 2022 | - |
dc.identifier.issn | 2073-4409 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/103216 | - |
dc.description.abstract | The prevalence of Alzheimer's disease (AD), the most common cause of age-associated dementia, is estimated to increase over the next decades. Evidence suggests neuro-immune signaling deregulation and risk genes beyond the amyloid-β (Aβ) deposition in AD pathology. We examined the temporal profile of inflammatory mediators and microglia deactivation/activation in the brain cortex and hippocampus of 3xTg-AD mice at 3- and 9-month-old. We found upregulated APP processing, decreased expression of CD11b, CX3CR1, MFG-E8, TNF-α, IL-1β, MHC-II and C/EBP-α and increased miR-146a in both brain regions in 3-month-old 3xTG-AD mice, suggestive of a restrictive regulation. Enhanced TNF-α, IL-1β, IL-6, iNOS, SOCS1 and Arginase 1 were only present in the hippocampus of 9-month-old animals, though elevation of HMGB1 and reduction of miR-146a and miR-124 were common features in the hippocampus and cortex regions. miR-155 increased early in the cortex and later in both regions, supporting its potential as a biomarker. Candidate downregulated target genes by cortical miR-155 included Foxo3, Runx2 and CEBPβ at 3 months and Foxo3, Runx2 and Socs1 at 9 months, which are implicated in cell survival, but also in Aβ pathology and microglia/astrocyte dysfunction. Data provide new insights across AD state trajectory, with divergent microglia phenotypes and inflammatory-associated features, and identify critical targets for drug discovery and combinatorial therapies. | pt |
dc.language.iso | eng | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject | Alzheimer’s disease | pt |
dc.subject | APP processing | pt |
dc.subject | dysregulated gene-associated biomarkers | pt |
dc.subject | inflammatory-associated miRNAs | pt |
dc.subject | microglia reactivity | pt |
dc.subject | miR-155 targets | pt |
dc.subject | 3xTg-AD mouse model | pt |
dc.subject.mesh | Alzheimer Disease | pt |
dc.subject.mesh | Animals | pt |
dc.subject.mesh | Disease Models, Animal | pt |
dc.subject.mesh | Disease Progression | pt |
dc.subject.mesh | Mice | pt |
dc.subject.mesh | Mice, Transgenic | pt |
dc.subject.mesh | Up-Regulation | pt |
dc.title | Differences in Immune-Related Genes Underlie Temporal and Regional Pathological Progression in 3xTg-AD Mice | pt |
dc.type | article | - |
degois.publication.firstPage | 137 | pt |
degois.publication.issue | 1 | pt |
degois.publication.title | Cells | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.3390/cells11010137 | pt |
degois.publication.volume | 11 | pt |
dc.date.embargo | 2022-01-01 | * |
uc.date.periodoEmbargo | 0 | pt |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | open | - |
item.openairetype | article | - |
item.languageiso639-1 | en | - |
item.fulltext | Com Texto completo | - |
item.cerifentitytype | Publications | - |
crisitem.author.orcid | 0000-0002-1200-4602 | - |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais IIIUC - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
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Differences-in-ImmuneRelated-Genes-Underlie-Temporal-and-Regional-Pathological-Progression-in-3xTgAD-MiceCells.pdf | 3.05 MB | Adobe PDF | View/Open |
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This item is licensed under a Creative Commons License