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Updated: Jun 14, 2025
Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins
Published on: August 15, 2017
Silencing miR-155-5p alleviates hippocampal damage in kainic acid-induced epileptic rats via the Dusp14/MAPK pathway
Qiong Fang1, Yuehao Cai1, Jiali Chi2
1Department of Pediatrics, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian 350001, China.
Abstract:
Epilepsy with recurrent seizures is characterized by neuronal damage and glial proliferation induced by brain inflammation. Recurrent seizures can lead to changes in the microRNA (miRNA) spectrum, significantly influencing the inflammatory response of microglia. MiR-155-5p, as a pro-inflammatory miRNA, is increased in the epileptic brain. However, its specific role in acute seizures remains unknown. The study aimed to develop a new strategy for treating epilepsy by investigating how silencing of miR-155-5p initiated its anticonvulsive mechanism. The level of miR-155-5p was up-regulated in the hippocampus of epileptic immature rats induced by kainic acid (KA). The use of antago-miR-155-5p exerted significant beneficial effects on the seizure scores, brain discharges and cognition in immature rats following KA-induced epilepsy. Antago-miR-155-5p also inhibited neuron damage and microglial activation. Moreover, the silencing of miR-155-5p significantly inhibited the Dual-specificity phosphatase 14 (Dusp14)/ mitogen-activated protein kinase (MAPK) axis in vivo. MiR-155-5p interacted with dusp14 to regulate MAPK signaling way expression, verified by a dual-luciferase reporter assay. The results suggested that the silencing of miR-155-5p might reduce hippocampal damage in epileptic immature rats induced by KA via Dusp14/MAPK signaling way. This implied that miR-155-5p could serve as a therapeutic tool to prevent the development of epilepsy.
Insights
Silencing microRNA-155-5p (miR-155-5p) reduces seizures and brain damage in epilepsy. This pro-inflammatory molecule targets the Dusp14/MAPK pathway, offering a potential new epilepsy treatment.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Epilepsy involves neuronal damage and inflammation, with microRNA (miRNA) spectrum changes influencing microglial response.
- Pro-inflammatory miR-155-5p is elevated in epileptic brains, but its role in acute seizures is unclear.
Purpose of the Study:
- Investigate the anticonvulsive mechanism of silencing miR-155-5p for potential epilepsy treatment.
- Determine the effect of miR-155-5p inhibition on kainic acid-induced epilepsy in immature rats.
Main Methods:
- Kainic acid (KA) induced epilepsy in immature rats to measure miR-155-5p levels.
- Administered antagomir-155-5p (antago-miR-155-5p) to assess effects on seizure scores, brain activity, cognition, neuronal damage, and microglial activation.
- Utilized dual-luciferase reporter assay to verify miR-155-5p interaction with Dusp14 and its regulation of the MAPK signaling pathway.
Main Results:
- miR-155-5p levels were significantly upregulated in the hippocampus of KA-induced epileptic rats.
- Antago-miR-155-5p treatment improved seizure scores, reduced brain discharges, enhanced cognition, and inhibited neuron damage and microglial activation.
- Silencing miR-155-5p suppressed the hippocampal Dusp14/MAPK signaling axis in vivo.
Conclusions:
- Silencing miR-155-5p demonstrates anticonvulsive effects in a rat epilepsy model.
- The therapeutic mechanism involves the inhibition of the Dusp14/MAPK pathway, reducing hippocampal damage.
- miR-155-5p represents a potential therapeutic target for preventing epilepsy development.
