MicroRNA-132 aggravates epileptiform discharges via suppression of BDNF/TrkB signaling in cultured hippocampal neurons.

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.