Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects

Nat Med. 2012 Jul;18(7):1087-94. doi: 10.1038/nm.2834.


Temporal lobe epilepsy is a common, chronic neurological disorder characterized by recurrent spontaneous seizures. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate post-transcriptional expression of protein-coding mRNAs, which may have key roles in the pathogenesis of neurological disorders. In experimental models of prolonged, injurious seizures (status epilepticus) and in human epilepsy, we found upregulation of miR-134, a brain-specific, activity-regulated miRNA that has been implicated in the control of dendritic spine morphology. Silencing of miR-134 expression in vivo using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21% and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus. Depletion of miR-134 after status epilepticus in mice reduced the later occurrence of spontaneous seizures by over 90% and mitigated the attendant pathological features of temporal lobe epilepsy. Thus, silencing miR-134 exerts prolonged seizure-suppressant and neuroprotective actions; determining whether these are anticonvulsant effects or are truly antiepileptogenic effects requires additional experimentation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • CA3 Region, Hippocampal / drug effects
  • CA3 Region, Hippocampal / metabolism
  • CA3 Region, Hippocampal / pathology
  • Cell Death / drug effects
  • Dendritic Spines / drug effects
  • Dendritic Spines / pathology
  • Epilepsy, Temporal Lobe / genetics
  • Epilepsy, Temporal Lobe / pathology
  • Gene Silencing* / drug effects
  • Humans
  • Kainic Acid / toxicity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / metabolism*
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / pathology
  • Real-Time Polymerase Chain Reaction
  • Recurrence
  • Seizures / genetics*
  • Seizures / prevention & control*
  • Status Epilepticus / genetics
  • Status Epilepticus / pathology
  • Up-Regulation / drug effects
  • Up-Regulation / genetics


  • MIRN134 microRNA, human
  • MicroRNAs
  • Mirn134 microRNA, mouse
  • Neuroprotective Agents
  • Kainic Acid