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.
Highlights
Temporal lobe epilepsy (TLE) is a common, intractable form of epilepsy in adults that is characterized by recurrent, unprovoked focal seizures originating from the temporal lobe [1]
TLE was successfully induced in rats A rat model of TLE was established by intraperitoneal injection of lithium chloride-pilocarpine
MiRNA-146a was up-regulated in the hippocampus of TLE rats miRNA-146a expression was detected in the hippocampus of rats by qRT-RCR, which showed that miRNA146a expression was significantly higher in the model group than in the control group (P < 0.05)
Summary
Temporal lobe epilepsy (TLE) is a common, intractable form of epilepsy in adults that is characterized by recurrent, unprovoked focal seizures originating from the temporal lobe [1]. Previous studies have shown that, in the hippocampus of TLE rats, miRNA-27a, − 54, − 210, − 345-3p, − 365-5p, − 4233p, and − 455-3p are significantly up-regulated, and miRNA-33, −135b, − 138, − 221, − 222 and − 296-5p are significantly down-regulated [10,11,12]. These miRNAs have diverse regulatory roles in TLE. Down-regulation of miRNA-2965p promotes neuronal apoptosis in the hippocampus of chronic TLE rats by activating caspase-3 [11]. The specific roles of miRNA-146a in the pathological changes that occur in TLE are still not fully understood
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