Anderson, Sean T. and Commins, Sean and Moynagh, Paul N. and Coogan, Andrew
(2015)
Lipopolysaccharide-induced sepsis induces long-lasting affective changes in the mouse.
Brain, Behavior, and Immunity, 43.
pp. 98-109.
ISSN 0889-1591
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; 5 mg/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.
| Item Type: |
Article
|
| Keywords: |
Sepsis; LPS; Behaviour; Cognition; Depression; Neuroinflammation; Hippocampus; |
| Academic Unit: |
Faculty of Science and Engineering > Psychology |
| Item ID: |
10711 |
| Identification Number: |
https://doi.org/10.1016/j.bbi.2014.07.007 |
| Depositing User: |
Dr. Sean Commins
|
| Date Deposited: |
09 Apr 2019 16:38 |
| Journal or Publication Title: |
Brain, Behavior, and Immunity |
| Publisher: |
Elsevier |
| Refereed: |
Yes |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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