Inhibition of indoleamine 2,3-dioxygenase 1/2 prevented cognitive impairment and energetic metabolism changes in the hippocampus of adult rats subjected to polymicrobial sepsis

J Neuroimmunol. 2017 Apr 15:305:167-171. doi: 10.1016/j.jneuroim.2017.02.001. Epub 2017 Feb 3.

Abstract

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection that may affect the brain. We investigated the role of indoleamine 2,3-dioxygenase (IDO-1/2) inhibition on long-term memory and energetic metabolism after experimental sepsis by caecal ligation and perforation (CLP). Experimental sepsis increased the activity of complexes I, II-III and IV at 24h after CLP, and IDO-1/2 inhibition normalized the activity of these complexes in the hippocampus. Wistar rats presented impairment of habituation and aversive memories 10days after CLP. Adjuvant treatment with the IDO inhibitor prevented long-term cognitive impairment triggered by sepsis.

Keywords: Cognitive impairment; Energetic metabolism; Indoleamine 2,3-dioxygenase 1/2; Sepsis.

MeSH terms

  • Animals
  • Avoidance Learning / drug effects
  • Cognition Disorders / etiology*
  • Cognition Disorders / metabolism*
  • Cognition Disorders / prevention & control*
  • Disease Models, Animal
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology*
  • Exploratory Behavior / drug effects
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Histocompatibility Antigens / metabolism
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
  • Inhibition, Psychological
  • Injections, Intra-Articular
  • Male
  • Rats
  • Rats, Wistar
  • Sepsis / complications*
  • Sepsis / etiology
  • Sepsis / microbiology
  • Statistics, Nonparametric
  • Sympathomimetics / pharmacology
  • Sympathomimetics / therapeutic use
  • p-Hydroxyamphetamine / pharmacology
  • p-Hydroxyamphetamine / therapeutic use

Substances

  • Histocompatibility Antigens
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Sympathomimetics
  • p-Hydroxyamphetamine