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J Neuroinflammation. 2016 May 16;13(1):108. doi: 10.1186/s12974-016-0572-0.

Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice.

Author information

1
Department of Pharmacology, Oxford University, Mansfield Road, OX1 3QT, Oxford, UK.
2
Division of Molecular Psychiatry, Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
3
Department of Neuroscience, Maastricht University, Universiteitssingel 40, NL 6229, ER, Maastricht, Netherlands.
4
Institute of Physiologically Active Compounds, Moscow Region, Russia.
5
Department of Anatomy, First Moscow Medical University, Moscow, Russia.
6
Department of Basic and Applied Neurobiology, Serbsky Federal Medical Research Center for Psychiatry and Narcology, Moscow, Russia.
7
Department of Preventive Medicine, Maastricht Medical Centre Annadal, Maastricht, Netherlands.
8
Department of Pharmacology, Oxford University, Mansfield Road, OX1 3QT, Oxford, UK. daniel.anthony@pharm.ox.ac.uk.
9
Department of Neuroscience, Maastricht University, Universiteitssingel 40, NL 6229, ER, Maastricht, Netherlands. t.strekalova@maastrichtuniversity.nl.

Abstract

BACKGROUND:

Aggression, hyperactivity, impulsivity, helplessness and anhedonia are all signs of depressive-like disorders in humans and are often reported to be present in animal models of depression induced by stress or by inflammatory challenges. However, chronic mild stress (CMS) and clinically silent inflammation, during the recovery period after an infection, for example, are often coincident, but comparison of the behavioural and molecular changes that underpin CMS vs a mild inflammatory challenge and impact of the combined challenge is largely unexplored. Here, we examined whether stress-induced behavioural and molecular responses are analogous to lipopolysaccharide (LPS)-induced behavioural and molecular effects and whether their combination is adaptive or maladaptive.

METHODS:

Changes in measures of hedonic sensitivity, helplessness, aggression, impulsivity and CNS and systemic cytokine and 5-HT-system-related gene expression were investigated in C57BL/6J male mice exposed to chronic stress alone, low-dose LPS alone or a combination of LPS and stress.

RESULTS:

When combined with a low dose of LPS, chronic stress resulted in an enhanced depressive-like phenotype but significantly reduced manifestations of aggression and hyperactivity. At the molecular level, LPS was a strong inducer of TNFα, IL-1β and region-specific 5-HT2A mRNA expression in the brain. There was also increased serum corticosterone as well as increased TNFα expression in the liver. Stress did not induce comparable levels of cytokine expression to an LPS challenge, but the combination of stress with LPS reduced the stress-induced changes in 5-HT genes and the LPS-induced elevated IL-1β levels.

CONCLUSIONS:

It is evident that when administered independently, both stress and LPS challenges induced distinct molecular and behavioural changes. However, at a time when LPS alone does not induce any overt behavioural changes per se, the combination with stress exacerbates depressive and inhibits aggressive behaviours.

KEYWORDS:

5-HT; Aggressive behaviour; Chronic stress; Cytokines; LPS; SERT

PMID:
27184538
PMCID:
PMC4867526
DOI:
10.1186/s12974-016-0572-0
[Indexed for MEDLINE]
Free PMC Article

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