Neurotrophin-3 mRNA a putative target of miR21 following status epilepticus

Status epilepticus induces a cascade of protein expression changes contributing to the subsequent development of epilepsy. By identifying the cascade of molecular changes that contribute to the development of epilepsy we hope to be able to design therapeutics for preventing epilepsy. MicroRNAs influence gene expression by altering mRNA stability and/or translation and have been implicated in the pathology of multiple diseases. MiR21 and its co-transcript miR21*, microRNAs produced from either the 5′ or 3′ ends of the same precursor RNA strand, are increased in the hippocampus following status epilepticus.We have identified a miR21 binding site, in the 3′ UTR of neurotrophin-3 that inhibits translation. Neurotrophin-3 mRNA levels decrease in the hippocampus following SE concurrent with the increase in miR21. MiR21 levels in cultured hippocampal neurons inversely correlate with neurotrophin-3 mRNA levels. Treatment of hippocampal neuronal cultures with excess K+Cl−, a depolarizing agent mimicking the episode of status epilepticus, also results in an increase in miR21 and a decrease in neurotrophin-3 mRNA. MiR21 is a candidate for regulating neurotrophin-3 signaling in the hippocampus following status epilepticus.

► Following status epilepticus miR21 increases in the hippocampus.
► Following status epilepticus neurotrophin-3 mRNA decreases in the hippocampus.
► The 3′ UTR of neurotrophin-3 mRNA has a miR21 binding site.
► In neuronal cultures miR21 levels are inversely related to neurotrophin-3 mRNA levels.