DSpace Repository

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

Show simple item record

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.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.06
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.04
dc.relation.issn 2073-4409


Files in this item

Files Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record

info:eu-repo/semantics/restrictedAccess Except where otherwise noted, this item's license is described as info:eu-repo/semantics/restrictedAccess

Search DSpace


Browse

My Account

Statistics