REST/NRSF transcription factor is overexpressed in hippocampus of patients with drug-resistant mesial temporal lobe epilepsy

Epilepsy Behav. 2019 May:94:118-123. doi: 10.1016/j.yebeh.2019.02.012. Epub 2019 Mar 21.

Abstract

The Repressor Element-1 Silencing Transcription factor or Neuron-Restrictive Silencer Factor (REST/NRSF) is a zinc finger repressor transcription factor of the Kruppel family. Several studies in experimental models have shown that overexpression of REST/NRSF occurs after the induction of seizures. In the present study, the expression of REST/NRSF (messenger ribonucleic acid (mRNA) and protein) was evaluated in the hippocampus of 28 patients with drug-resistant mesial temporal lobe epilepsy (MTLE) and their correlation with clinical variables and comorbid anxiety and depression. The REST/NRSF protein expression was augmented in an age-dependent manner in the hippocampus of autopsied subjects. However, this condition was not observed in patients with MTLE, in whom overexpression of this transcription factor occurred at both the mRNA and protein levels. The correlations with clinical variables showed that the frequency of epileptic seizures was proportional to the protein expression of REST/NRSF. The results revealed that the overexpression of REST/NRSF was more evident in patients with MTLE without anxiety and depression. Our data indicate that the expression of REST/NRSF is modified in patients with MTLE. This condition has implications in the pathophysiology of this disorder, making it a potential candidate for the optimization of clinical treatments.

Keywords: Hippocampus; Mesial temporal lobe epilepsy; Psychiatric comorbidities; REST/NRSF; Seizure frequency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anxiety / complications
  • Anxiety / genetics
  • Anxiety / metabolism
  • Depression / complications
  • Depression / genetics
  • Depression / metabolism
  • Drug Resistant Epilepsy / complications
  • Drug Resistant Epilepsy / genetics
  • Drug Resistant Epilepsy / metabolism*
  • Epilepsy, Temporal Lobe / complications
  • Epilepsy, Temporal Lobe / genetics
  • Epilepsy, Temporal Lobe / metabolism*
  • Female
  • Gene Expression Regulation
  • Hippocampus / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Neurons / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Young Adult

Substances

  • RE1-silencing transcription factor
  • Repressor Proteins