title: The microRNA miR-124 suppresses seizure activity and regulates CREB1 activity.
abstract: miR-124, a brain-specific microRNA, was originally considered as a key regulator in neuronal differentiation and the development of the nervous system. Here we showed that miR-124 expression was suppressed in patients with epilepsy and rats after drug induced-seizures. Intrahippocampal administration of a miR-124 duplex led to alleviated seizure severity and prolonged onset latency in two rat models (pentylenetetrazole- and pilocarpine-induced seizures), while miR-124 inhibitor led to shortened onset latency in pilocarpine-induced seizure rat models. Moreover, the result of local field potentials (LFPs) records further demonstrated miR-124 may have anti-epilepsy function. Inhibition of neuronal firing by miR-124 was associated with the suppression of mEPSC, AMPAR- and NMDAR-mediated currents, which were accompanied by decreased surface expression of NMDAR. In addition, miR-124 injection resulted in decreased activity and expression of cAMP-response element-binding protein1 (CREB1). a key regulator in epileptogenesis. A dual-luciferase reporter assay was used to confirm that miR-124 targeted directly the 3'UTR of CREB1 gene and repressed the CREB1 expression in HEK293T cells. Immunoprecipitation studies confirmed that the CREB1 antibody effectively precipitated CREB1 and NMDAR1 but not GLUR1 from rat brain hippocampus. These results revealed a previously unknown function of miR-124 in neuronal excitability and provided a new insight into molecular mechanisms underlying epilepsy.
authors.affiliation: Department of Neurology,Chongqing Key Laboratory of Neurology,The First Affiliated Hospital of Chongqing Medical University,1 Youyi Road,Chongqing 400016,China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurology,Chongqing Key Laboratory of Neurology,The First Affiliated Hospital of Chongqing Medical University,1 Youyi Road,Chongqing 400016,China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology,Chongqing Key Laboratory of Neurology,The First Affiliated Hospital of Chongqing Medical University,1 Youyi Road,Chongqing 400016,China.
authors.forename: Lang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurology,Chongqing Key Laboratory of Neurology,The First Affiliated Hospital of Chongqing Medical University,1 Youyi Road,Chongqing 400016,China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology,Chongqing Key Laboratory of Neurology,The First Affiliated Hospital of Chongqing Medical University,1 Youyi Road,Chongqing 400016,China.
authors.forename: Zucai
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Neurology,Chongqing Key Laboratory of Neurology,The First Affiliated Hospital of Chongqing Medical University,1 Youyi Road,Chongqing 400016,China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurology,Chongqing Key Laboratory of Neurology,The First Affiliated Hospital of Chongqing Medical University,1 Youyi Road,Chongqing 400016,China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Department of Neurology,Chongqing Key Laboratory of Neurology,The First Affiliated Hospital of Chongqing Medical University,1 Youyi Road,Chongqing 400016,China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology,Chongqing Key Laboratory of Neurology,The First Affiliated Hospital of Chongqing Medical University,1 Youyi Road,Chongqing 400016,China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Peking University School of Medicine,38 Xueyuan Road,Beijing 100091,China.
authors.forename: KeWei
authors.initials: K
authors.lastname: Wang
authors.affiliation: The Institute of Biophysics,Chinese Academy of Sciences,15 Datun Road,Beijing 100101,China.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurology,Chongqing Key Laboratory of Neurology,The First Affiliated Hospital of Chongqing Medical University,1 Youyi Road,Chongqing 400016,China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Neurology,Chongqing Key Laboratory of Neurology,The First Affiliated Hospital of Chongqing Medical University,1 Youyi Road,Chongqing 400016,China.
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D004827:Epilepsy / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010433:Pentylenetetrazole / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D035683:MicroRNAs; D010433:Pentylenetetrazole; D010862:Pilocarpine; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C508137:Creb1 protein, rat; C548144:MIRN124 microRNA, rat