Keap1-Nrf2 signaling pathway confers resilience versus susceptibility to inescapable electric stress

Eur Arch Psychiatry Clin Neurosci. 2018 Dec;268(8):865-870. doi: 10.1007/s00406-017-0848-0. Epub 2017 Nov 8.

Abstract

The transcription factor Keap1-Nrf2 signaling plays a key role in the oxidative stress which is involved in psychiatric disorders. In the learned helplessness (LH) paradigm, protein levels of Keap1 and Nrf2 in the prefrontal cortex and dentate gyrus of hippocampus from LH (susceptible) rats were lower than control and non-LH (resilience) rats. Furthermore, protein expressions of Keap1 and Nrf2 in the parietal cortex from major depressive disorder, schizophrenia, and bipolar disorder were lower than controls. These results suggest that Keap1-Nrf2 signaling might contribute to stress resilience which plays a key role in the pathophysiology of psychiatric disorders.

Keywords: Learned helplessness; Oxidative stress; Postmortem brain; Resilience.

MeSH terms

  • Analysis of Variance
  • Animals
  • Brain / metabolism*
  • Disease Models, Animal
  • Electroshock / adverse effects*
  • Gene Expression Regulation / physiology
  • Helplessness, Learned
  • Humans
  • Kelch-Like ECH-Associated Protein 1 / metabolism*
  • Male
  • Mental Disorders / metabolism
  • Mental Disorders / pathology
  • NF-E2-Related Factor 2 / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / physiology*
  • Stress, Psychological / etiology
  • Stress, Psychological / pathology*
  • Time Factors

Substances

  • KEAP1 protein, rat
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat