Evidence map›Paper›PMID 26969530›Full record

ArticleNeurobiology of disease2016

Anti-NMDA receptor autoantibodies and associated neurobehavioral pathology in mice are dependent on age of first exposure to Toxoplasma gondii.

Geetha Kannan, Joshua A Crawford, ChunXia Yang, Kristin L Gressitt, Chinezimuzo Ihenatu, Irina N Krasnova, Jean Lud Cadet, Robert H Yolken, Emily G Severance, Mikhail V Pletnikov

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
5.7field-weighted citation impact, top 4% 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

21 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
  2. Article
  3. Prevalence ofMicroorganisms · 2024
    Article
  4. Toxoplasma-induced behavior changes - is microbial dysbiosis the missing link?Frontiers in cellular and infection microbiology · 2024
    Review
  5. Review
  6. Review
  7. Review
  8. Epigenetic Manipulation of Psychiatric Behavioral Disorders Induced byFrontiers in cellular and infection microbiology · 2022
    Review
  9. Neurological and Neurobehavioral Disorders Associated withJournal of parasitology research · 2021
    Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. A NewScientifica · 2018
    Article
  17. Review
  18. Article
  19. From Toxoplasmosis to SchizophreniaFrontiers in psychiatry · 2017
    Article
  20. Article
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 2 institutions in 1 country.

Geetha KannanDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA. Electronic address: KannanG17@gmail.com.
Joshua A CrawfordDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA.
ChunXia YangDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA.
Kristin L GressittStanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Chinezimuzo IhenatuStanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Irina N KrasnovaMolecular Neuropsychiatry Research Branch, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
Jean Lud CadetMolecular Neuropsychiatry Research Branch, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
Robert H YolkenStanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Emily G SeveranceStanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Mikhail V PletnikovDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA; Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Johns Hopkins University · USNational Institutes of Health · US

Funding

Project 3P50MH094268 · NIMH · JOHNS HOPKINS UNIVERSITY · PI SAWA, AKIRA · 2011 to 2020
$19.9M
Mutant DISC 1 and Abnormal Neurodevelopment in Mental IllnessR01MH083728 · NIMH · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI PLETNIKOV, MIKHAIL V · 2009 to 2020
$4.9M
NIMH NIH HHS P50 MH094268NIMH NIH HHS R01 MH083728
6 · The paper itself

Abstract

backgroundToxoplasma gondii is a pathogen implicated in psychiatric disorders. As elevated antibodies to T. gondii are also present in non-symptomatic individuals, we hypothesized that the age during first exposure to the pathogen may affect symptom manifestation. We tested this hypothesis by evaluating neurobehavioral abnormalities and the immune response in mice following adolescent or adult T. gondii infection.

methodsMice were infected with T. gondii at postnatal day 33 (adolescent/juvenile) or 61 (adult). At 8weeks post-infection (wpi), pre-pulse inhibition of the acoustic startle (PPI) in mice administered MK-801 (0.1 and 0.3mg/kg) and amphetamine (5 and 10mg/kg) was assessed. Peripheral (anti-T. gondii, C1q-associated IgG and anti-GLUN2 antibodies) and central (C1q and Iba1) markers of the immune response were also evaluated. In addition, regional brain expression of N-methyl-d-aspartate receptor (NMDAR) subunits (GLUN1 and GLUN2A), glutamatergic (vGLUT1, PSD95) and GABAergic (GAD67) markers, and monoamines (DA, NE, 5-HT) and their metabolites were measured.

resultsJuvenile and adult infected mice exhibited opposite effects of MK-801 on PPI, with decreased PPI in juveniles and increased PPI in adults. There was a significantly greater elevation of GLUN2 autoantibodies in juvenile-compared to adult-infected mice. In addition, age-dependent differences were found in regional expression of NMDAR subunits and markers of glutamatergic, GABAergic, and monoaminergic systems. Activated microglia and C1q elevations were found in both juvenile- and adult-T. gondii infected mice.

conclusionsOur study demonstrates that the age at first exposure to T. gondii is an important factor in shaping distinct behavioral and neurobiological abnormalities. Elevation in GLUN2 autoantibodies or complement protein C1q may be a potential underlying mechanism. A better understanding of these age-related differences may lead to more efficient treatments of behavioral disorders associated with T. gondii infection.

Indexed as

ToxoplasmaAgingAnimalsAutoantibodiesBrainImmunoglobulin GMaleMental DisordersMice, Inbred BALB CReceptors, N-Methyl-D-AspartateToxoplasmosisAutoantibodiesImmunoglobulin GReceptors, N-Methyl-D-AspartateAutoantibodyC1qNeurodevelopmentNMDARSchizophreniaToxoplasma

Identifiers

PMID26969530
PMCPMC5506683
OpenAlexW2294480362

What OpenQuestion holds

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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.