Lasting downregulation of the lipid peroxidation enzymes in the prefrontal cortex of mice susceptible to stress-induced anhedonia

Behav Brain Res. 2015 Jan 1;276:118-29. doi: 10.1016/j.bbr.2014.04.037. Epub 2014 Apr 28.

Abstract

Antioxidant enzymes and lipid peroxidation in the brain are involved in neuropsychiatric pathologies, including depression. 14- or 28-day chronic stress model induced a depressive syndrome defined by lowered reward sensitivity in C57BL/6J mice and changed gene expression of peroxidation enzymes as shown in microarray assays. We studied how susceptibility or resilience to anhedonia is related to lipid peroxidation in the prefrontal cortex (PFC). With 14-day stress, a comparison of the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX) and accumulation of malondialdehyde (MDA) revealed a decrease of the first two measures in susceptible, but not in resilient animals or in stressed mice chronically dosed with imipramine (7mg/kg/day). Acute stress elevated activity of CAT and SOD and dynamics of MDA accumulation in the PFC that was prevented by imipramine (30mg/kg). 28-day stress evoked anhedonia lasting two but not five weeks while behavioural invigoration was detected at the latter time point in anhedonic but not non-anhedonic mice; enhanced aggressive traits were observed in both groups. After two weeks of a stress-free period, CAT and SOD activity levels in the PFC were reduced in anhedonic animals; after five weeks, only CAT was diminished. Thus, in the present chronic stress depression paradigm, lasting alterations in brain peroxidation occur not only during anhedonia but also in the recovery period and are accompanied by behavioural abnormalities in mice. This mimics behavioural and neurochemical deficits observed in depressed patients during remission which could be used to develop remedies preventing their relapse.

Keywords: Anhedonia; Chronic stress depression model; Imipramine; Lipid peroxidation; Microarray; Prefrontal cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression / drug effects
  • Anhedonia* / drug effects
  • Animals
  • Catalase / genetics
  • Catalase / metabolism
  • Down-Regulation*
  • Food Preferences
  • Gene Expression Profiling
  • Gene Expression Regulation, Enzymologic / drug effects
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Hippocampus / metabolism
  • Imipramine / pharmacology
  • Lipid Peroxidation / drug effects
  • Lipid Peroxidation / genetics*
  • Male
  • Malondialdehyde / metabolism
  • Mice
  • Motor Activity / drug effects
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / enzymology*
  • Resilience, Psychological
  • Stress, Psychological / enzymology*
  • Stress, Psychological / genetics
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism

Substances

  • Malondialdehyde
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Imipramine