Universidad Peruana Cayetano Heredia

Intrahippocampal Inoculation of Aβ1–42 Peptide in Rat as a Model of Alzheimer’s Disease Identified MicroRNA-146a-5p as Blood Marker with Anti-Inflammatory Function in Astrocyte Cells

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dc.contributor.author Aquino Ordinola, Ruth Elizabeth
dc.contributor.author de Concini, Vidian
dc.contributor.author Dhenain, Marc
dc.contributor.author Lam, Suzanne
dc.contributor.author Gosset, David
dc.contributor.author Baquedano Santana, Laura Estefania
dc.contributor.author Forero, Manuel G
dc.contributor.author Menuet, Arnaud
dc.contributor.author Baril, Patrick
dc.contributor.author Pichon, Chantal
dc.date.accessioned 2023-03-23T15:49:33Z
dc.date.available 2023-03-23T15:49:33Z
dc.date.issued 2023
dc.identifier.uri https://hdl.handle.net/20.500.12866/13274
dc.description.abstract Circulating microRNAs (miRNAs) have aroused a lot of interest as reliable blood diagnostic biomarkers of Alzheimer's disease (AD). Here, we investigated the panel of expressed blood miRNAs in response to aggregated Aβ<sub>1-42</sub> peptides infused in the hippocampus of adult rats to mimic events of the early onset of non-familial AD disorder. Aβ<sub>1-42</sub> peptides in the hippocampus led to cognitive impairments associated with an astrogliosis and downregulation of circulating miRNA-146a-5p, -29a-3p, -29c-3p, -125b-5p, and-191-5p. We established the kinetics of expression of selected miRNAs and found differences with those detected in the APP<sub>swe</sub>/PS1<sub>dE9</sub> transgenic mouse model. Of note, miRNA-146a-5p was exclusively dysregulated in the Aβ-induced AD model. The treatment of primary astrocytes with Aβ<sub>1-42</sub> peptides led to miRNA-146a-5p upregulation though the activation of the NF-κB signaling pathway, which in turn downregulated IRAK-1 but not TRAF-6 expression. As a consequence, no induction of IL-1β, IL-6, or TNF-α was detected. Astrocytes treated with a miRNA-146-5p inhibitor rescued IRAK-1 and changed TRAF-6 steady-state levels that correlated with the induction of IL-6, IL-1β, and CXCL1 production, indicating that miRNA-146a-5p operates anti-inflammatory functions through a NF-κB pathway negative feedback loop. Overall, we report a panel of circulating miRNAs that correlated with Aβ<sub>1-42</sub> peptides' presence in the hippocampus and provide mechanistic insights into miRNA-146a-5p biological function in the development of the early stage of sporadic AD. en_US
dc.language.iso eng
dc.publisher MDPI
dc.relation.ispartofseries Cells
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject microRNAs en_US
dc.subject miRNA-146a-5p en_US
dc.subject Alzheimer’s disease en_US
dc.subject Aβ1–42 peptide en_US
dc.subject biomarkers en_US
dc.subject diagnosis en_US
dc.subject.mesh MicroARNs
dc.subject.mesh Enfermedad de Alzheimer
dc.subject.mesh Biomarcadores
dc.subject.mesh Diagnóstico
dc.title Intrahippocampal Inoculation of Aβ1–42 Peptide in Rat as a Model of Alzheimer’s Disease Identified MicroRNA-146a-5p as Blood Marker with Anti-Inflammatory Function in Astrocyte Cells en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.3390/cells12050694
dc.relation.issn 2073-4409


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