Antagonist Targeting microRNA-155 Protects against Lithium-Pilocarpine-Induced Status Epilepticus in C57BL/6 Mice by Activating Brain-Derived Neurotrophic Factor

Abstract

Epilepsy is a severe brain disorder affecting numerous patients. Recently, it is inferred that modulation of microRNA-155 (miR-155) could serve as a promising treatment of mesial temporal lobe epilepsy. In the current study, the therapeutic potential of miR-155 antagonist against temporal lobe epilepsy (TLE) was evaluated and the underlying mechanism involved in this regulation was explored. TLE model was induced by lithium-pilocarpine method. The effect of miR-155 antagonist on epilepticus symptoms of TLE mice was assessed using Racine classification and electroencephalogram (EEG) recordings. The expression of brain-derived neurotrophic factor (BDNF) and its association with miR-155 were also assessed with a series of experiments. Our results showed that level of miR-155 was significantly up-regulated after induction of TLE model. Based on the results of EEG and behavior analyses, seizures in mice were alleviated by miR-155 antagonist. Moreover, administration of miR-155 antagonist also significantly increased the level of BDNF. The results of dual luciferase assay and Western blotting showed that miR-155 antagonist exerted its action on status epilepticus by directly regulating the activity of BDNF. Taken all the information together, our results demonstrated that miR-155 antagonist might firstly induce the expression of BDNF, which then contributed to the alleviation of epilepsy in the current study.

Manipulating MicroRNAs in Murine Models: Targeting the Multi-Targeting in Epilepsy

“…A recent study showed that delivery of antagomirs targeting microRNA-155 prior to status epilepticus induced by pilocarpine in mice resulted in a trend toward lower mortality and lower scores in a Racine-type behavioral assessment and suggested brain-derived neurotrophic factor as a possible target. The effects of the antagomir on post-status epilepticus epilepsy or neuropathology were not reported (36).…”

NR4A1 Knockdown Suppresses Seizure Activity by Regulating Surface Expression of NR2B

“…Meanwhile, the brain tissue samples of the neocortex with TLE could only be obtained from drug-resistant epileptic patients. For this reason, a pilocarpine-induced epileptic mouse model that has been broadly used as a model for human TLE has obvious advantages in repeating the results of the epileptic patients284546. Thus, we performed our study on brain tissues of both TLE patients and experimental mice using two complementary methods to further investigate the expression of NR4A1 and the potential mechanism of TLE.…”

The antiepileptic effect of Gastrodiae Rhizoma through modulating overexpression of mTOR and attenuating astrogliosis in pilocarpine mice model

“…We adopted the pilocarpine‐induced SE model of mice, which is a well‐established chemical‐induced model for TLE. Although the use of lithium is not universal, recent studies used lithium, combined with scopolamine, to reduce the overall pilocarpine dose in a mice TLE model . Pilocarpine is a muscarinic acetylcholine receptor agonist acting on M1 subunit of G protein–coupled receptors that damages the hippocampus, resulting in the generation of SE .…”