title: MicroRNA-132 aggravates epileptiform discharges via suppression of BDNF/TrkB signaling in cultured hippocampal neurons.
abstract: MicroRNAs (miRs) are increasingly recognized as targets to prevent or disrupt epilepsy as well as serve as diagnostic biomarkers of epileptogenesis. Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin related kinase type B (TrkB) also contribute to the pathophysiology of epilepsy. However, the possible involvement of miRs in BDNF-mediated molecular basis for epileptogenesis is less understood. In the present study, we found a dramatic upregulation of miR-132 and BDNF mRNA in the hippocampal neuronal culture model of status epilepticus (SE) obtained by Mg(2+)-free treatment. To investigate the role of miR-132 in the pathogenesis of epilepsy mediated by BDNF/TrkB signaling, we used a transfection approach to overexpress miR-132, and then detected a consequential decrease in BDNF mRNA and BDNF-dependent full-length TrkB receptor (TrkB.FL) signaling activity in the epileptic neurons. We investigated the alterations of epileptiform discharges in the hippocampal neuronal culture model of SE using the whole-cell patch-clamp technique. Activation of TrkB.FL by pretreatment with BDNF partly inhibited the Mg(2+)-free induced continuous high-frequency epileptiform discharges, while overexpression of miR-132 exacerbated epileptiform discharges. MiR-132 was also implicated in the postepileptic enhancement of high voltage dependent calcium channel. These results suggest that miR-132 promotes epileptogenesis through regulating BDNF/TrkB signaling in the hippocampal neuronal culture model of SE.
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; Department of Neurology, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin 300060, 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: Hao
authors.initials: H
authors.lastname: Cai
authors.affiliation: VIP Ward, Tianjin Medical University General Hospital and Tianjin Neurological Institute, Tianjin, 300052, China.
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: songyijun2000@126.com.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Song
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D004827:Epilepsy / Q000503:physiopathology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000503:physiopathology*; D008275:Magnesium Deficiency; D008564:Membrane Potentials / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020813:Receptor, trkB / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015220:Calcium Channels; D035683:MicroRNAs; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D020813:Receptor, trkB
keywords: BDNF; Calcium channel; MiR-132; Status epilepticus; TrkB.FL