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Publication : Antagomir-mediated suppression of microRNA-134 reduces kainic acid-induced seizures in immature mice.

First Author  Campbell A Year  2021
Journal  Sci Rep Volume  11
Issue  1 Pages  340
PubMed ID  33431894 Mgi Jnum  J:300288
Mgi Id  MGI:6502322 Doi  10.1038/s41598-020-79350-7
Citation  Campbell A, et al. (2021) Antagomir-mediated suppression of microRNA-134 reduces kainic acid-induced seizures in immature mice. Sci Rep 11(1):340
abstractText  MicroRNAs are short non-coding RNAs that negatively regulate protein levels and perform important roles in establishing and maintaining neuronal network function. Previous studies in adult rodents have detected upregulation of microRNA-134 after prolonged seizures (status epilepticus) and demonstrated that silencing microRNA-134 using antisense oligonucleotides, termed antagomirs, has potent and long-lasting seizure-suppressive effects. Here we investigated whether targeting microRNA-134 can reduce or delay acute seizures in the immature brain. Status epilepticus was induced in 21 day-old (P21) male mice by systemic injection of 5 mg/kg kainic acid. This triggered prolonged electrographic seizures and select bilateral neuronal death within the CA3 subfield of the hippocampus. Expression of microRNA-134 and functional loading to Argonaute-2 was not significantly changed in the hippocampus after seizures in the model. Nevertheless, when levels of microRNA-134 were reduced by prior intracerebroventricular injection of an antagomir, kainic acid-induced seizures were delayed and less severe and mice displayed reduced neuronal death in the hippocampus. These studies demonstrate targeting microRNA-134 may have therapeutic applications for the treatment of seizures in children.
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