title: MiR-134 blockade prevents status epilepticus like-activity and is neuroprotective in cultured hippocampal neurons.
abstract: Status epilepticus (SE) is a life-threatening neurological disorder associated with significant morbidity and mortality. MicroRNAs (miRNAs) are small, non-coding RNAs that act post-transcriptionally modulating messenger RNA (mRNA) translation or stability which may have important roles in the pathogenesis of epilepsy. It has been reported that silencing microRNA-134 in vivo has significant neuroprotective and prolonged seizure-suppressive effects. However, the mechanism by which miR-134 inhibition suppressed seizures and whether miR-134 inhibition works in an in vitro model of SE, is unknown. Compared to a complex in vivo system, in vitro models of SE-like electrographic activity can be powerful tools to study this miRNA. Using a cell culture model of low Mg(2+) treatment of rat hippocampal neurons, we found SE-like electrographic activity increased expression of miR-134. Inhibiting expression of miR-134 using an inhibitor lentivirus with two miR-134 binding sites reduced SE-like electrographic activity in the hippocampal neurons and reduced neuronal death. This study provides direct evidence that inhibition of miR-134 can block status epilepticus-like discharges and is neuroprotective in hippocampal neuronal cultures and implies that inhibiting miR-134 may be a potential candidate for the clinical treatment of SE.
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiao-Mu
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Department of Neurology, People's Liberation Army 457th Hospital, Wuhan 430012, China.
authors.forename: Rui-Hua
authors.initials: RH
authors.lastname: Jia
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wei
authors.affiliation: Tianjin Neurological Institute, Tianjin 30052, China.
authors.forename: Wei-Yun
authors.initials: WY
authors.lastname: Cui
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: jiangwen@fmmu.edu.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D016086:Lentivirus / Q000235:genetics; D054461:Lim Kinases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D061251:Primary Cell Culture; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000378:metabolism / Q000503:physiopathology*
chemical_list: C581995:MIRN134 microRNA, rat; D035683:MicroRNAs; D054461:Lim Kinases; C515894:Limk1 protein, rat
keywords: Hippocampal cultures; Lentivirus; MiR-134; Status epilepticus