Silencing of microRNA-146a alleviates the neural damage in temporal lobe epilepsy by down-regulating Notch-1

• Published in: Molecular brain 2019-12, Vol.12 (1), p.102-102, Article 102
• Main Authors: Huang, Hui, Cui, Guiyun, Tang, Hai, Kong, Lingwen, Wang, Xiaopeng, Cui, Chenchen, Xiao, Qihua, Ji, Huiming
• Format: Article
• Language: English
• Subjects: Anopheles; Apoptosis; Brain; Caspase-9; Convulsions & seizures; Enzyme-linked immunosorbent assay; Epilepsy; Experiments; Genes; Genetic research; Glial fibrillary acidic protein; Hippocampus; IL-1β; Interleukin 18; Interleukin 6; Laboratory animals; Lithium; Lithium chloride; Lithium compounds; Luciferase; MicroRNA; microRNA-146a; MicroRNAs; miRNA; Neuronal damage; Neurons; Notch-1; Notch1 protein; Pilocarpine; Reporter gene; Rodents; Scientific equipment industry; siRNA; Temporal lobe; Temporal lobe epilepsy
• ISSN: 1756-6606; 1756-6606
• DOI: 10.1186/s13041-019-0523-7

This study aimed to evaluate the specific regulatory roles of microRNA-146a (miRNA-146a) in temporal lobe epilepsy (TLE) and explore the related regulatory mechanisms. A rat model of TLE was established by intraperitoneal injection of lithium chloride-pilocarpine. These model rats were injected intracerebroventricularly with an miRNA-146a inhibitor and Notch-1 siRNA. Then, neuronal damage and cell apoptosis in the cornu ammonis (CA) 1 and 3 regions of the hippocampus were assessed. SOD and MDA levels in the hippocampus were detected by chromatometry, and IL-1β, IL-6, and IL-18 levels were detected by ELISA. Then, we evaluated the expression levels of caspase-9, GFAP, Notch-1, and Hes-1 in the hippocampus. The interaction between Notch-1 and miRNA-146a was assessed by a dual luciferase reporter gene assay. A rat model of TLE was successfully established, which exhibited significantly increased miRNA-146a expression in the hippocampus. Silencing of miRNA-146a significantly alleviated the neuronal damage and cell apoptosis in the CA1 and CA3 regions of the hippocampus in TLE rats and decreased MDA, IL-1β, IL-6, and IL-18 levels and increased SOD levels in the hippocampus of TLE rats. In addition, silencing of miRNA-146a significantly decreased the expression levels of caspase-9, GFAP, Notch-1, and Hes-1 in the hippocampus of TLE rats. Notch-1 was identified as a target of miRNA-146a and silencing of Notch-1 aggravated the neuronal damage in the CA1 and CA3 regions. Silencing of miRNA-146a alleviated the neuronal damage in the hippocampus of TLE rats by down-regulating Notch-1.