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Expression profiling the microRNA response to epileptic preconditioning identifies miR-184 as a modulator of seizure-induced neuronal death
- Source :
-
Experimental Neurology . Oct2012, Vol. 237 Issue 2, p346-354. 9p. - Publication Year :
- 2012
-
Abstract
- 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. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 00144886
- Volume :
- 237
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Experimental Neurology
- Publication Type :
- Academic Journal
- Accession number :
- 79995426
- Full Text :
- https://doi.org/10.1016/j.expneurol.2012.06.029