Evidence map›Paper›PMID 27184538›Full record

ArticleJournal of neuroinflammation2016

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

Yvonne Couch, Alexander Trofimov, Natalyia Markova, Vladimir Nikolenko, Harry W Steinbusch, Vladimir Chekhonin, Careen Schroeter, Klaus-Peter Lesch, Daniel C Anthony, Tatyana Strekalova

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.

  1. What Animal Models Can Tell Us About Long-Term Psychiatric Symptoms in Sepsis Survivors: a Systematic Review.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021
    Pooled it
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  9. Erythropoietin (EPO) Alleviates Chronic Stress-Induced Depression by Modulating SIRT1-Mediated Mitochondrial Function.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
    Article
  10. Pentoxifylline Prevents Neuroinflammation and Modifies PTEN/TrkB Signaling in an LPS-Induced Depression Model.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 7 institutions in 4 countries.

Yvonne CouchDepartment of Pharmacology, Oxford University, Mansfield Road, OX1 3QT, Oxford, UK.
Alexander TrofimovDivision of Molecular Psychiatry, Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
Natalyia MarkovaDepartment of Neuroscience, Maastricht University, Universiteitssingel 40, NL 6229, ER, Maastricht, Netherlands.
Vladimir NikolenkoDepartment of Anatomy, First Moscow Medical University, Moscow, Russia.
Harry W SteinbuschDepartment of Neuroscience, Maastricht University, Universiteitssingel 40, NL 6229, ER, Maastricht, Netherlands.
Vladimir ChekhoninDepartment of Basic and Applied Neurobiology, Serbsky Federal Medical Research Center for Psychiatry and Narcology, Moscow, Russia.
Careen SchroeterDepartment of Preventive Medicine, Maastricht Medical Centre Annadal, Maastricht, Netherlands.
Klaus-Peter LeschDivision of Molecular Psychiatry, Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
Daniel C AnthonyDepartment of Pharmacology, Oxford University, Mansfield Road, OX1 3QT, Oxford, UK. daniel.anthony@pharm.ox.ac.uk.
Tatyana StrekalovaDepartment of Neuroscience, Maastricht University, Universiteitssingel 40, NL 6229, ER, Maastricht, Netherlands. t.strekalova@maastrichtuniversity.nl.
Maastricht University · NLUniversity of Oxford · GBFederal Medical Research Centre for Psychiatry and Narcology · RUInstitute of Physiologically Active Compounds · RUMaastricht University Medical Centre · NLSechenov University · RUUniversity of Würzburg · DE

Funding

Biotechnology and Biological Sciences Research Council
6 · The paper itself

Abstract

backgroundAggression, 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.

methodsChanges 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.

resultsWhen 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.

conclusionsIt 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.

Indexed as

Disease Models, AnimalAggressionAnimalsChronic DiseaseDepressionLipopolysaccharidesMaleMiceMice, Inbred C57BLRandom AllocationRats, WistarStress, PsychologicalLipopolysaccharides5-HTAggressive behaviourChronic stressCytokinesLPSSERT

Identifiers

PMID27184538
PMCPMC4867526
OpenAlexW2404523827

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.