کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6262581 1613802 2016 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research ReportMicroRNA-204 suppresses epileptiform discharges through regulating TrkB-ERK1/2-CREB signaling in cultured hippocampal neurons
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Research ReportMicroRNA-204 suppresses epileptiform discharges through regulating TrkB-ERK1/2-CREB signaling in cultured hippocampal neurons
چکیده انگلیسی


- MiR-204 was downregulated in the Mg2+-free model in hippocampal neurons.
- MiR-204 regulated TrkB mRNA expression in cultured hippocampal neurons.
- PLCγ1 and ERK1/2-CREB pathways were activated in the Mg2+-free model.
- ERK1/2-CREB signaling pathway was inhibited by miR-204 under SE condition.
- MiR-204 inhibited Mg2+-free induced epileptiform discharges in hippocampal neurons.

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 Mg2+-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 Mg2+-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 Mg2+-free model in hippocampal neurons through regulating TrkB and downstream ERK1/2-CREB signaling pathway.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1639, 15 May 2016, Pages 99-107
نویسندگان
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