MicroRNA-451 Aggravates Kainic Acid-induced Seizure and Neuronal Apoptosis by Targeting GDNF

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Author(s): Ning Weng, Jingbo Sun, Shixiang Kuang, Hai Lan, Qiansong He, Hui Yang, Lin Zhang, Hong Xue*.

Journal Name: Current Neurovascular Research

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Aim: Epilepsy is a common, serious neurological disease that causes recurrent episodes =but the molecular mechanism remains unclear. Abnormal miRNA expression is associated with epilepsy, including miR-451. This research was to investigate the role of miR-451 in seizure and the detail mechanism.

Methods: The seizure mice model was induced by kainic acid (KA) injection to the right lateral cerebral ventricle. Behavioral changes of mice were observed and evaluated by the Racine Scale. The miR-451 knockout mice were established by adenovirus infection. The in vitro model was performed by miR-451 mimics transfected HEK-293 cells. The amount of neuronal death and morphological changes were evaluated by Nissl staining and H&E staining.

Results: The results showed that miR-451 is up regulating in KA-induced seizure models and miR-451 knockout decreased the behavior score and improved the pathological changes of the hippocampus. Besides, MiR-451 knockout inhibited the apoptosis of hippocampal neurons. Bioinformatics studies have shown that glial cell line-derived neurotrophic factor (GDNF) is a target gene of miR-451. MiR-451 could negatively regulate the expression of GDNF. GDNF overexpression could reverse the effect of miR-451 on KA induced brain injury and neuronal apoptosis.

Conclusion: This research demonstrates that miR-451 can affect the behavior of KA-induced epilepsy mice and hippocampal neuronal damage by regulating GDNF expression. The results would provide an experimental foundation for further research about the potential contribution of miRNAs to epilepsy pathophysiology.

Keywords: MicroRNA-451, Seizure, Glial cell line-derived neurotrophic factor (GDNF), Neuronal apoptosis

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(E-pub Ahead of Print)
DOI: 10.2174/1567202617666191223150510
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