Therapeutic Effect of Idebenone on Rats with Vascular Dementia via the MicroRNA-216a/RSK2/NF-κB Axis
Authors Qian X, Xu Q, Li G, Bu Y, Sun F, Zhang J
Received 23 November 2020
Accepted for publication 25 January 2021
Published 17 February 2021 Volume 2021:17 Pages 533—543
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Yuping Ning
Xudong Qian,1 Qianqian Xu,1 Guoyun Li,2 Yi Bu,1 Fan Sun,1 Jian Zhang1
1Department of Neurology, Affiliated Hospital of Chengde Medical University, Chengde, 067000, Hebei, People’s Republic of China; 2Department of Respiratory, Affiliated Hospital of Chengde Medical University, Chengde, 067000, Hebei, People’s Republic of China
Correspondence: Jian Zhang
Department of Neurology, Affiliated Hospital of Chengde Medical University, No. 36, Nanyingzi Street, Chengde, 067000, Hebei, People’s Republic of China
Tel/Fax +86 0314-2279965
Background: Vascular dementia (VD) is a brain disease featured by cognitive impairment and cerebrovascular pathologies. Idebenone can treat neurodegenerative diseases. This study evaluated the mechanism of Idebenone in VD.
Methods: The VD rat model was established by permanent occlusion of bilateral common carotid arteries, followed by intragastrical administration of Idebenone. The learning and spatial memory abilities, and the levels of MDA, SOD, IL-6 and TNF-α were measured. Histological staining was adopted to observe the damage of neurons in the hippocampal cortex and to quantitatively analyze the neuronal damage in CA1 area of hippocampus. Microarray analysis was performed to find out the effect of Idebenone treatment on microRNA (miR) expression in hippocampus of rats. The potential target genes of miR and the pathways regulated by target genes were searched by bioinformatics analysis, and verified by experiments. The mechanism of action behind Idebenone in VD rats was proved by rescue experiment.
Results: Idebenone treatment improved the learning and spatial memory abilities of VD rats, inhibited neuroinflammation and oxidative stress, and prevented neuronal apoptosis. Idebenone treatment elevated miR-216a expression in hippocampus of rats, but the therapeutic effect of Idebenone was averted by lentivirus inhibition of miR-216a. miR-216a targeted RSK2. Overexpression of RSK2 annulled the therapeutic effect of Idebenone on VD rats by activating the IκBα/NF-κB axis.
Conclusion: Idebenone inhibits the activation of RSK2/IκBα/NF-κB axis by increasing miR-216a, thus alleviating oxidative stress and neuroinflammation in VD rats.
Keywords: vascular dementia, idebenone, microRNA-216a, RSK2, IκBα/NFκB, oxidative stress
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