title: Expression profiling the microRNA response to epileptic preconditioning identifies miR-184 as a modulator of seizure-induced neuronal death.
abstract: Brief seizures (epileptic/seizure preconditioning) are capable of activating endogenous protective pathways in the brain which can temporarily generate a damage-refractory state against subsequent and otherwise harmful episodes of prolonged seizures (tolerance). Altered expression of microRNAs, a class of non-coding RNAs that function post-transcriptionally to regulate mRNA translation has recently been implicated in the molecular mechanism of epileptic tolerance. Here we characterized the effect of seizure preconditioning induced by low-dose systemic kainic acid on microRNA expression in the hippocampus of mice. Seizure preconditioning resulted in up-regulation of 25 mature microRNAs in the CA3 subfield of the mouse hippocampus, with the highest levels detected for miR-184. This finding was supported by real time PCR and in situ hybridization showing increased neuronal miR-184 levels and a reduction in protein levels of a miR-184 target. Inhibiting miR-184 expression in vivo resulted in the emergence of neuronal death after preconditioning seizures and increased seizure-induced neuronal death following status epilepticus in previously preconditioned animals, without altered electrographic seizure durations. The present study suggests miRNA up-regulation after preconditioning may contribute to development of epileptic tolerance and identifies miR-184 as a novel contributor to neuronal survival following both mild and severe seizures.
authors: Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
authors: Ross C
authors: RC
authors: McKiernan
authors: Eva M
authors: EM
authors: Jimenez-Mateos
authors: Takanori
authors: T
authors: Sano
authors: Isabella
authors: I
authors: Bray
authors: Raymond L
authors: RL
authors: Stallings
authors: Roger P
authors: RP
authors: Simon
authors: David C
authors: DC
authors: Henshall
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016923:Cell Death / Q000235:genetics; D003292:Convulsants / Q000008:administration & dosage; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D017403:In Situ Hybridization; D007608:Kainic Acid / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012640:Seizures / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D003292:Convulsants; C552233:MIRN184 microRNA, mouse; D035683:MicroRNAs; D007608:Kainic Acid