Therapeutic Effect of Idebenone on Rats with Vascular Dementia via the MicroRNA-216a/RSK2/NF-κB Axis
Open Access
- 1 February 2021
- journal article
- research article
- Published by Taylor & Francis Ltd in Neuropsychiatric Disease and Treatment
- Vol. ume 17, 533-543
- https://doi.org/10.2147/ndt.s293614
Abstract
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
This publication has 37 references indexed in Scilit:
- The Role of Oxidative Damage in the Pathogenesis and Progression of Alzheimer’s Disease and Vascular DementiaOxidative Medicine and Cellular Longevity, 2015
- Assessment and management of behavioral and psychological symptoms of dementiaBMJ, 2015
- Idebenone and neuroprotection: antioxidant, pro-oxidant, or electron carrier?Journal of Bioenergetics and Biomembranes, 2014
- Neuroprotective Effects of Idebenone Against Pilocarpine-Induced Seizures: Modulation of Antioxidant Status, DNA Damage and Na+, K+-ATPase Activity in Rat HippocampusNeurochemical Research, 2014
- The Pathobiology of Vascular DementiaNeuron, 2013
- MicroRNA-195Protects Against Dementia Induced by Chronic Brain Hypoperfusion via Its Anti-Amyloidogenic Effect in RatsJournal of Neuroscience, 2013
- Idebenone Prevents Human Optic Nerve Head Astrocytes From Oxidative Stress, Apoptosis, and Senescence by Stabilizing BAX/Bcl-2 RatioJournal of Glaucoma, 2013
- RSK2 mediates NF‐κB activity through the phosphorylation of IκBα in the TNF‐R1 pathwayThe FASEB Journal, 2010
- Inflammatory Mediators in the Frontal Lobe of Patients with Mixed and Vascular DementiaDementia and Geriatric Cognitive Disorders, 2008
- Long-term idebenone treatment of vascular and degenerative brain disorders of the elderlyArchives of Gerontology and Geriatrics, 1992