Therapeutic Effect of Idebenone on Rats with Vascular Dementia via the MicroRNA-216a/RSK2/NF-κB Axis
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, 067...
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Dove Medical Press
2021
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oai:doaj.org-article:5d828a956e4145549bd139a19d9dda292021-12-02T12:17:51ZTherapeutic Effect of Idebenone on Rats with Vascular Dementia via the MicroRNA-216a/RSK2/NF-κB Axis1178-2021https://doaj.org/article/5d828a956e4145549bd139a19d9dda292021-02-01T00:00:00Zhttps://www.dovepress.com/therapeutic-effect-of-idebenone-on-rats-with-vascular-dementia-via-the-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Xudong 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 ChinaCorrespondence: Jian ZhangDepartment of Neurology, Affiliated Hospital of Chengde Medical University, No. 36, Nanyingzi Street, Chengde, 067000, Hebei, People’s Republic of ChinaTel/Fax +86 0314-2279965Email Zhangjian8141@163.comBackground: 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 stressQian XXu QLi GBu YSun FZhang JDove Medical Pressarticlevascular dementiaidebenonemicrorna-216arsk2iκbα/nfκboxidative stressNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 17, Pp 533-543 (2021) |
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DOAJ |
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vascular dementia idebenone microrna-216a rsk2 iκbα/nfκb oxidative stress Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 |
| spellingShingle |
vascular dementia idebenone microrna-216a rsk2 iκbα/nfκb oxidative stress Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Qian X Xu Q Li G Bu Y Sun F Zhang J Therapeutic Effect of Idebenone on Rats with Vascular Dementia via the MicroRNA-216a/RSK2/NF-κB Axis |
| description |
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 ChinaCorrespondence: Jian ZhangDepartment of Neurology, Affiliated Hospital of Chengde Medical University, No. 36, Nanyingzi Street, Chengde, 067000, Hebei, People’s Republic of ChinaTel/Fax +86 0314-2279965Email Zhangjian8141@163.comBackground: 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 |
| format |
article |
| author |
Qian X Xu Q Li G Bu Y Sun F Zhang J |
| author_facet |
Qian X Xu Q Li G Bu Y Sun F Zhang J |
| author_sort |
Qian X |
| title |
Therapeutic Effect of Idebenone on Rats with Vascular Dementia via the MicroRNA-216a/RSK2/NF-κB Axis |
| title_short |
Therapeutic Effect of Idebenone on Rats with Vascular Dementia via the MicroRNA-216a/RSK2/NF-κB Axis |
| title_full |
Therapeutic Effect of Idebenone on Rats with Vascular Dementia via the MicroRNA-216a/RSK2/NF-κB Axis |
| title_fullStr |
Therapeutic Effect of Idebenone on Rats with Vascular Dementia via the MicroRNA-216a/RSK2/NF-κB Axis |
| title_full_unstemmed |
Therapeutic Effect of Idebenone on Rats with Vascular Dementia via the MicroRNA-216a/RSK2/NF-κB Axis |
| title_sort |
therapeutic effect of idebenone on rats with vascular dementia via the microrna-216a/rsk2/nf-κb axis |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/5d828a956e4145549bd139a19d9dda29 |
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