Aim: Epilepsy is a common and serious neurological disease that causes recurrent episodes,
but its molecular mechanism remains unclear. Abnormal miRNA expression is associated
with epilepsy, including miR-451. This research investigated the role of miR-451 in seizure and its
Methods: The seizure mice model was induced by kainic acid (KA) injection to the right lateral
cerebral ventricle. Behavioral changes in 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 regulated 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 mi-
RNAs to epilepsy pathophysiology.