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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2022

Open Access 01-12-2022 | Alzheimer's Disease | Research

MicroRNA-22-3p ameliorates Alzheimer’s disease by targeting SOX9 through the NF-κB signaling pathway in the hippocampus

Authors: Pengcheng Xia, Jing Chen, Yingchao Liu, Xiaolin Cui, Cuicui Wang, Shuai Zong, Le Wang, Zhiming Lu

Published in: Journal of Neuroinflammation | Issue 1/2022

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Abstract

Background

Studies have suggested that many down-regulated miRNAs identified in the brain tissue or serum of Alzheimer’s disease (AD) patients were involved in the formation of senile plaques and neurofibrillary tangles. Specifically, our previous study revealed that microRNA-22-3p (miR-22-3p) was significantly down-regulated in AD patients. However, the molecular mechanism underlying the down-regulation of miR-22-3p has not been comprehensively investigated.

Methods

The ameliorating effect of miR-22-3p on apoptosis of the Aβ-treated HT22 cells was detected by TUNEL staining, flow cytometry, and western blotting. The cognition of mice with stereotaxic injection of agomir or antagomir of miR-22-3p was assessed by Morris water maze test. Pathological changes in the mouse hippocampus were analyzed using hematoxylin and eosin (HE) staining, Nissl staining, and immunohistochemistry. Proteomics analysis was performed to identify the targets of miR-22-3p, which were further validated using dual-luciferase reporter analysis and western blotting analysis.

Results

The miR-22-3p played an important role in ameliorating apoptosis in the Aβ-treated HT22 cells. Increased levels of miR-22-3p in the mouse hippocampus improved the cognition in mice. Although the miR-22-3p did not cause the decrease of neuronal loss in the hippocampus, it reduced the Aβ deposition. Proteomics analysis revealed Sox9 protein as the target of miR-22-3p, which was verified by the luciferase reporter experiments.

Conclusion

Our study showed that miR-22-3p could improve apoptosis and reduce Aβ deposition by acting on Sox9 through the NF-κB signaling pathway to improve the cognition in AD mice. We concluded that miR-22-3p ameliorated AD by targeting Sox9 through the NF-κB signaling pathway in the hippocampus.
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Metadata
Title
MicroRNA-22-3p ameliorates Alzheimer’s disease by targeting SOX9 through the NF-κB signaling pathway in the hippocampus
Authors
Pengcheng Xia
Jing Chen
Yingchao Liu
Xiaolin Cui
Cuicui Wang
Shuai Zong
Le Wang
Zhiming Lu
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2022
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-022-02548-1

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