期刊
LABORATORY INVESTIGATION
卷 100, 期 9, 页码 1223-1237出版社
ELSEVIER SCIENCE INC
DOI: 10.1038/s41374-020-0444-1
关键词
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资金
- Youth Foundation of The First Affiliated Hospital of Zhengzhou University [YNQN2017108]
- Henan Provincial Science and Technology Research Project [201701008]
- National Natural Science Foundation of China [81300685]
This study reveals that inhibition of miR-181a-5p protects immature rats from epilepsy, including hippocampal insults, neuronal apoptosis, astrocyte and microglia activation, neuroinflammation, and oxidative stress. This protection is achieved through the SIRT1 pathway, which may be a novel therapeutic target for epilepsy. MicroRNAs regulate gene expression at the posttranscriptional level, and this process has been shown to be implicated in the pathological processes of temporal lobe epilepsy. At present, studies about the impact of microRNA-181a (miR-181a) on epilepsy have focused on hippocampal neurons, and the effect of miR-181a on other cells in the hippocampus remains poorly understood. Herein, we explored the role of miR-181a-5p in a lithium-pilocarpine model of epilepticus in immature rats. We found that the hippocampal expression level of miR-181a-5p was increased. Inhibition of miR-181a-5p protected the hippocampus against epilepsy, including hippocampal insults, neuronal apoptosis, astrocyte and microglia activation, neuroinflammation, oxidative stress, mitochondrial function, and cognitive dysfunction. Moreover, miR-181a-5p inhibition exerted a seizure-suppressing effect via SIRT1 upregulation. Overall, our findings reveal the potential role of the miR-181a-5p/SIRT1 pathway in the development of temporal lobe epilepsy, and this pathway may represent a novel target for ameliorating epilepsy and its sequelae.
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