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 |
|