Lipopolysaccharide-induced sepsis induces long-lasting affective changes in the mouse

Seán T Anderson, Seán Commins, Paul N Moynagh, Andrew N Coogan

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Post-septic encephalopathy is a poorly understood condition in survivors of sepsis that is characterised by cognitive and affective impairments. In this study we have sought to better understand this condition by undertaking a comprehensive behavioural and cognitive assessment of mice who had previously survived sepsis. Mice were treated with lipopolysaccharide (LPS; 5mg/kg) and one month after this assessed on a battery of tests. Post-septic animals were found to display significantly more immobility in the tail suspension test and show a significantly decreased sucrose preference. Acute fluoxetine treatment reversed the increase in immobility in the tail suspension test in post-septic animals. Post-septic animals also showed less overall exploratory behaviour in the novel object recognition task and also showed increased anxiety-like behaviour in the elevated plus maze. Post-septic mice did not show signs of cognitive impairment, as assessed in the Morris watermaze, the 8-arm radial maze or on preference for the novel object in the novel object recognition task. Immunohistochemical analysis revealed significant upregulation of the microglial marker CD-11b, F4/80 and IBA-1 in the hippocampus of post-septic animals, as well as significant downregulation of the plasticity-related immediate early gene products ARC and EGR1. We also observed a decrease in neural stem cell proliferation in the dentate gyrus of post-septic animals as judged by BrdU incorporation. Co-treatment with the NF-κB pathway inhibitor PDTC attenuated the long-lasting effects of LPS on most of the affected parameters, but not on neural stem cell proliferation. These results show that LPS-induced sepsis in the mouse is followed by long-lasting increases in depressive- and anxiety-like behaviours, as well as by changes in neuroinflammatory- and neural plasticity-associated factors, and that attenuation of the severity of sepsis by PDTC attenuates many of these effects.

Original languageEnglish
Pages (from-to)98-109
Number of pages12
JournalBrain, Behavior and Immunity
Volume43
Early online date22 Jul 2014
DOIs
Publication statusPublished - Jan 2015

Keywords

  • Animals
  • Antidepressive Agents
  • Anxiety
  • Behavior, Animal
  • Cytoskeletal Proteins
  • Depression
  • Disease Models, Animal
  • Early Growth Response Protein 1
  • Exploratory Behavior
  • Fluoxetine
  • Hippocampus
  • Lipopolysaccharides
  • Maze Learning
  • Mice
  • Nerve Tissue Proteins
  • Sepsis
  • Journal Article

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