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Silencing of MicroRNA-146a Alleviates the Neural Damage in Temporal Lobe Epilepsy by Down-regulating Notch-1

Overview
Journal Mol Brain
Publisher Biomed Central
Date 2019 Dec 5
PMID 31796120
Citations 10
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Abstract

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.

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References
1.
Coenen A, van Luijtelaar E . Genetic animal models for absence epilepsy: a review of the WAG/Rij strain of rats. Behav Genet. 2003; 33(6):635-55. DOI: 10.1023/a:1026179013847. View

2.
Ding M, Haglid K, Hamberger A . Quantitative immunochemistry on neuronal loss, reactive gliosis and BBB damage in cortex/striatum and hippocampus/amygdala after systemic kainic acid administration. Neurochem Int. 2000; 36(4-5):313-8. DOI: 10.1016/s0197-0186(99)00139-4. View

3.
Roch C, Leroy C, Nehlig A, Namer I . Magnetic resonance imaging in the study of the lithium-pilocarpine model of temporal lobe epilepsy in adult rats. Epilepsia. 2002; 43(4):325-35. DOI: 10.1046/j.1528-1157.2002.11301.x. View

4.
Kuida K, Haydar T, Kuan C, Gu Y, Taya C, Karasuyama H . Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell. 1998; 94(3):325-37. DOI: 10.1016/s0092-8674(00)81476-2. View

5.
Coyle A, Riley J, Wu C, Sharan A . From resection to ablation: A review of resective surgical options for temporal lobe epilepsy and rationale for an ablation-based approach. Neurol India. 2017; 65(Supplement):S71-S77. DOI: 10.4103/0028-3886.201662. View