title: MicroRNA-204 suppresses epileptiform discharges through regulating TrkB-ERK1/2-CREB signaling in cultured hippocampal neurons.
abstract: MicroRNAs (miRs) have been increasingly recognized as post-transcriptional regulators involved in the pathogenesis of epilepsy. Extensive evidence suggests that inhibition of tropomyosin related kinase type B (TrkB) signaling limits epileptogenesis. It has been reported that miR-204 directly targeted and downregulated TrkB protein in a variety of cancers to suppress tumorigenesis, but its effect on epileptogenesis is unknown. Here we showed that miR-204 was downregulated in cultured hippocampal neurons following status epilepticus (SE) induced by Mg(2+)-free treatment. Overexpression of miR-204 using a transfection technique negatively regulated the expression of TrkB mRNA. Insight into the downstream signaling pathway activated by TrkB may provide valuable clues to the underlying mechanisms of epileptogenesis. Biochemical measures revealed activation of phospholipase Cγ1 (PLCγ1), extracellular signal-regulated kinase1/2 (ERK1/2) and cAMP response-element binding protein (CREB) signaling molecules in the Mg(2+)-free model in hippocampal neurons, of which ERK1/2-CREB but not PLCγ1 signaling pathway was able to be inhibited by miR-204. Epileptiform discharges assessed using whole-cell current-clamp techniques were suppressed by miR-204 in cultured hippocampus neurons of SE. These results suggest that miR-204 exerts an antiepileptogenic effect in the Mg(2+)-free model in hippocampal neurons through regulating TrkB and downstream ERK1/2-CREB signaling pathway.
authors.affiliation: Department of Neurology, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin 300060, China; Department of Neurology, Tianjin Medical University General Hospital, Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin Neurological Institute, Tianjin 300052, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xiang
authors.affiliation: Department of Neurology, Tianjin Medical University General Hospital, Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin Neurological Institute, Tianjin 300052, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Neurology, Tianjin Medical University General Hospital, Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin Neurological Institute, Tianjin 300052, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Li
authors.affiliation: Senior Officials inpatient Ward Tianjin Medical University General Hospital and Tianjin Neurological Institute, Tianjin 300052, China. Electronic address: zhaowen2@yahoo.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Tianjin Medical University General Hospital, Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin Neurological Institute, Tianjin 300052, China. Electronic address: songyj@tmu.edu.cn.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Song
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004827:Epilepsy / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008275:Magnesium Deficiency; D008564:Membrane Potentials / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051966:Phospholipase C gamma / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism; D014162:Transfection
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C000620955:MIRN204 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger; D020813:Receptor, trkB; D051966:Phospholipase C gamma
keywords: CREB; ERK1/2; PLCγ1; Status epilepticus; TrkB; miRNA-204