Function And Mechanism Of MiR-132on Epileptogeniesis

PART ONE：EXPRESSION OF P-CREB ANDACTIVITY-DEPENDENT MIR-132IN TEMPORAL LOBEEPILEPSYObjective To investigate the expression of p-CREB and miR-132inseizure focus of intractable epilepsy patients；To investigate the expressionof p-CREB and miR-132in hippocampus of TLE models at different timesafter induced SE.Methods1.15intractable epilepsy patients and10control objects with nosignificantly differences on age and gender were included from which thetemporal neocortex were surgically removed. For comparison,Temporal lobe epilepsy (TLE) was induced in rodents, and the brain tissueswere collected.2. P-CREB expression was detected by Western blot assay andimmunochemistry at6h,24h,3d,7d,14d,30d and60d after inducedstatus epilepsy (SE), respectively, and in patients with TLE. 3. The expression of miR-132was detected by RT-PCR.Results1. Expression of p-CREB was significantly increased in the patientswith TLE and the induced TLE rat model.2. Expression of miR-132was decreased significantly in the braintissue of patients with TLE. But the expression of miR-132was increasedsignificantly in the hippocampus of TLE model at the times24h and7dafter induced SE, however there were no significant differences at the othertimes.Conclusions The expression of p-CREB and miR-132was increasedin epilepsy rats during the acute and latent phases, suggesting a possiblepathogenetic role of p-CREB and miR-132in TLE via modulating thedendritic plasticity.PART TWO：OUTCOME OF THE PROGRESS OFEPILEPTOGENIESIS THROUGH SILENCING MIR-132Objective This study aimed to investigate the role of microRNA-132in the epileptogenesis.Methods Temporal lobe epilepsy (TLE) was induced in rodents, andthe brain tissues were collected. These rodents were pretreated withAnt-132or Scr（non-targeting Scrambled sequence）.We applied thebehavioral observation, and the brain tissues were detected by NPY immunochemistry and Golgi staining after induced status epilepsy (SE)Results Our study showed that silencing miR-132in rat usingantago-miRs prolonged the times which were used to induce SE andsuppressed evoked seizures, the occurrence of spontaneous seizures. Wealso found that MFS（mossy fiber sprouting）and outgrowth of dendriteswere significantly suppressed.Conclusions Silencing miR-132suppressed the occurrence ofspontaneous seizures, and the function worked out may through regulatingthe outgrowth of dendrites in CA3which resulted in the decreased neuralcircuit; whether these were anti-convulsant effects or were trulyanti-epileptogenic effects required additional experimentation.