Evidence map›Paper›PMID 34610039›Full record

ArticlePloS one2021

Behavioral alterations in long-term Toxoplasma gondii infection of C57BL/6 mice are associated with neuroinflammation and disruption of the blood brain barrier.

Leda Castaño Barrios, Ana Paula Da Silva Pinheiro, Daniel Gibaldi, Andrea Alice Silva, Patrícia Machado Rodrigues E Silva, Ester Roffê, Helton da Costa Santiago, Ricardo Tostes Gazzinelli, José Roberto Mineo, Neide Maria Silva and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

42 citing papers in PubMed, 55 citations in OpenAlex.

  1. Review
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  20. Frontiers in cellular and infection microbiology · 2025
    Review
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

11 authors at 5 institutions in 2 countries.

Leda Castaño BarriosLaboratory of Biology of the Interactions, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.
Ana Paula Da Silva PinheiroLaboratory of Biology of the Interactions, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.
Daniel GibaldiLaboratory of Biology of the Interactions, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.
Andrea Alice SilvaMultiuser Laboratory for Research Support in Nephrology and Medical Sciences, Federal University Fluminense, Niterói, Rio de Janeiro, Brazil.ORCID 0000-0001-5856-6128
Patrícia Machado Rodrigues E SilvaLaboratory of Inflammation, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.
Ester RoffêLaboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Helton da Costa SantiagoDepartment of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Ricardo Tostes GazzinelliDepartment of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
José Roberto MineoInstitute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
Neide Maria SilvaInstitute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
Joseli Lannes-VieiraLaboratory of Biology of the Interactions, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.ORCID 0000-0001-5503-6754
Fundação Oswaldo Cruz · BRUniversidade Federal de Minas Gerais · BRUniversidade Federal de Uberlândia · BRNational Institutes of Health · USUniversidade Federal Fluminense · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Apicomplexa protozoan Toxoplasma gondii is a mandatory intracellular parasite and the causative agent of toxoplasmosis. This illness is of medical importance due to its high prevalence worldwide and may cause neurological alterations in immunocompromised persons. In chronically infected immunocompetent individuals, this parasite forms tissue cysts mainly in the brain. In addition, T. gondii infection has been related to mental illnesses such as schizophrenia, bipolar disorder, depression, obsessive-compulsive disorder, as well as mood, personality, and other behavioral changes. In the present study, we evaluated the kinetics of behavioral alterations in a model of chronic infection, assessing anxiety, depression and exploratory behavior, and their relationship with neuroinflammation and parasite cysts in brain tissue areas, blood-brain-barrier (BBB) integrity, and cytokine status in the brain and serum. Adult female C57BL/6 mice were infected by gavage with 5 cysts of the ME-49 type II T. gondii strain, and analyzed as independent groups at 30, 60 and 90 days postinfection (dpi). Anxiety, depressive-like behavior, and hyperactivity were detected in the early (30 dpi) and long-term (60 and 90 dpi) chronic T. gondii infection, in a direct association with the presence of parasite cysts and neuroinflammation, independently of the brain tissue areas, and linked to BBB disruption. These behavioral alterations paralleled the upregulation of expression of tumor necrosis factor (TNF) and CC-chemokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β and CCL5/RANTES) in the brain tissue. In addition, increased levels of interferon-gamma (IFNγ), TNF and CCL2/MCP-1 were detected in the peripheral blood, at 30 and 60 dpi. Our data suggest that the persistence of parasite cysts induces sustained neuroinflammation, and BBB disruption, thus allowing leakage of cytokines of circulating plasma into the brain tissue. Therefore, all these factors may contribute to behavioral changes (anxiety, depressive-like behavior, and hyperactivity) in chronic T. gondii infection.

Indexed as

Behavior, AnimalAnimalsAnxietyBlood-Brain BarrierBrain EdemaChronic DiseaseCytokinesDepressionFemaleInflammationLocomotionMiceMice, Inbred C57BLMuscle StrengthParasitesTime FactorsCytokines

Identifiers

PMID34610039
PMCPMC8491889
OpenAlexW3203853710

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.