miR-96 attenuates status epilepticus-induced brain injury by directly targeting Atg7 and Atg16L1

Sci Rep. 2017 Aug 31;7(1):10270. doi: 10.1038/s41598-017-10619-0.

Abstract

Status epilepticus (SE) can cause brain damage and lead to neural dysfunction. Developing novel targets for SE therapy and diagnosis is important and necessary. Previously, we found several differentially expressed microRNAs (miRNAs) in the developing hippocampus following SE, including the autophagy-related miR-96. In the present study, we employed immunofluorescence staining and Western blot analysis to assess the expression of autophagy-related 7 (Atg7) and Atg16L1 and the status of autophagosome formation in the hippocampus of immature rats with SE. Additional in vivo intervention was also performed to investigate the potential therapeutic function of miR-96 in developing rats with SE. We found that Atg7 and Atg16L1 were up-regulated in the neurons after SE, together with an increase in autophagosome formation. Meanwhile, overexpression of miR-96 significantly prevented brain damage in SE rats by inhibiting Atg7 and Atg16L1 expression and autophagosome formation in the hippocampus. Furthermore, Rapamycin negated miR-96 mediated brain injury attenuation through inducing autophagosome formation. Our study indicates that miR-96 might be a potential target for therapy of pediatric SE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagosomes / metabolism
  • Autophagy / genetics
  • Autophagy-Related Protein 7 / genetics*
  • Autophagy-Related Protein 7 / metabolism
  • Biomarkers
  • Brain / metabolism
  • Brain / pathology
  • Disease Models, Animal
  • Gene Expression Regulation*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • MicroRNAs / genetics*
  • RNA Interference*
  • Rats
  • Status Epilepticus / genetics*
  • Status Epilepticus / metabolism
  • Status Epilepticus / pathology*
  • Vesicular Transport Proteins / genetics

Substances

  • Biomarkers
  • MIRN96 microRNA, rat
  • MicroRNAs
  • Vesicular Transport Proteins
  • Atg16L1 protein, rat
  • Autophagy-Related Protein 7