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https://hdl.handle.net/10316/103216
Title: | Differences in Immune-Related Genes Underlie Temporal and Regional Pathological Progression in 3xTg-AD Mice | Authors: | Fernandes, Adelaide Caldeira, Cláudia Cunha, Carolina Ferreiro, Elisabete Vaz, Ana Rita Brites, Dora |
Keywords: | Alzheimer’s disease; APP processing; dysregulated gene-associated biomarkers; inflammatory-associated miRNAs; microglia reactivity; miR-155 targets; 3xTg-AD mouse model | Issue Date: | 2022 | Serial title, monograph or event: | Cells | Volume: | 11 | Issue: | 1 | 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. | URI: | https://hdl.handle.net/10316/103216 | ISSN: | 2073-4409 | DOI: | 10.3390/cells11010137 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais IIIUC - Artigos em Revistas Internacionais |
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