Antagonist Targeting microRNA-155 Protects against Lithium-Pilocarpine-Induced Status Epilepticus in C57BL/6 Mice by Activating Brain-Derived Neurotrophic Factor.
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.
Department of Neurology, The First Affiliated Hospital of Dalian Medical University Dalian, China.
Zhengxu
Z
Cai
Center for Translational Research on Neurological Diseases, The First Affiliated Hospital of Dalian Medical University Dalian, China.
Song
S
Li
Department of Neurology, The First Affiliated Hospital of Dalian Medical University Dalian, China.
Sheng
S
Li
Department of Neurology, The First Affiliated Hospital of Dalian Medical University Dalian, China.
Fan
F
Song
Department of Neurology, The First Affiliated Hospital of Dalian Medical University Dalian, China.
Zhen
Z
Zhang
Department of Neurology, The First Affiliated Hospital of Dalian Medical University Dalian, China.
Guanhua
G
Qi
Center for Translational Research on Neurological Diseases, The First Affiliated Hospital of Dalian Medical University Dalian, China.
Tianbai
T
Li
Central Laboratory, The First Affiliated Hospital of Dalian Medical University Dalian, China.
Juanjuan
J
Qiu
Central Laboratory, The First Affiliated Hospital of Dalian Medical University Dalian, China.
Jiajia
J
Wan
Central Laboratory, The First Affiliated Hospital of Dalian Medical UniversityDalian, China; Institute of Basic Research of Integrative Medicine, Dalian Medical UniversityDalian, China.
Hua
H
Sui
Department of Neurology, The First Affiliated Hospital of Dalian Medical UniversityDalian, China; Central Laboratory, The First Affiliated Hospital of Dalian Medical UniversityDalian, China.
Huishu
H
Guo
antagonist; brain-derived neurotrophic factor; epilepsy; lithium-pilocarpine; microRNA-155