Evidence map›Paper›PMID 25522431›Full record

ArticleThe international journal of neuropsychopharmacology2014

Toll-like receptor expression in the blood and brain of patients and a mouse model of Parkinson's disease.

Janelle Drouin-Ouellet, Isabelle St-Amour, Martine Saint-Pierre, Jérôme Lamontagne-Proulx, Jasna Kriz, Roger A Barker, Francesca Cicchetti

Open access · bronzeAbstract read
In one paragraph

Article in The international journal of neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 7% 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

83 citing papers in PubMed, 1 synthesis or guideline pooled it, 151 citations in OpenAlex.

  1. A Systematic Review of Phytochemistry, Pharmacology and Pharmacokinetics onInternational journal of molecular sciences · 2019
    Pooled it
  2. Review
  3. Progress of Immunotherapies in Parkinson's Disease.CNS neuroscience & therapeutics · 2026
    Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. The microbiota-gut-brain axis: a potential target in the small-molecule compounds and gene therapeutic strategies for Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Review
  11. Review
  12. Article
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  16. Lysosomal storage, impaired autophagy and innate immunity in Gaucher and Parkinson's diseases: insights for drug discovery.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024
    Review
  17. Article
  18. Article
  19. Article
  20. Review

23 more citing papers are in PubMed but not listed here.

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

7 authors at 3 institutions in 2 countries.

Janelle Drouin-OuelletDepartment of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom (Drs Drouin-Ouellet and Barker); Centre de recherche du CHU de Québec, Québec, QC, Canada (Dr St-Amour, Ms Saint-Pierre, Mr Lamontagne-Proulx, and Dr Cicchetti); Centre de Recherche de l'Institut Universitaire en Santé Mentale de Québec, Québec, QC, Canada (Dr Kriz); and Département de psychiatrie et neurosciences, Université Laval, Québec, QC, Canada (Drs Kriz and Cicchetti). jd628@cam.ac.uk francesca.cicchetti@crchudequebec.ulaval.ca.
Isabelle St-AmourDepartment of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom (Drs Drouin-Ouellet and Barker); Centre de recherche du CHU de Québec, Québec, QC, Canada (Dr St-Amour, Ms Saint-Pierre, Mr Lamontagne-Proulx, and Dr Cicchetti); Centre de Recherche de l'Institut Universitaire en Santé Mentale de Québec, Québec, QC, Canada (Dr Kriz); and Département de psychiatrie et neurosciences, Université Laval, Québec, QC, Canada (Drs Kriz and Cicchetti).
Martine Saint-PierreDepartment of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom (Drs Drouin-Ouellet and Barker); Centre de recherche du CHU de Québec, Québec, QC, Canada (Dr St-Amour, Ms Saint-Pierre, Mr Lamontagne-Proulx, and Dr Cicchetti); Centre de Recherche de l'Institut Universitaire en Santé Mentale de Québec, Québec, QC, Canada (Dr Kriz); and Département de psychiatrie et neurosciences, Université Laval, Québec, QC, Canada (Drs Kriz and Cicchetti).
Jérôme Lamontagne-ProulxDepartment of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom (Drs Drouin-Ouellet and Barker); Centre de recherche du CHU de Québec, Québec, QC, Canada (Dr St-Amour, Ms Saint-Pierre, Mr Lamontagne-Proulx, and Dr Cicchetti); Centre de Recherche de l'Institut Universitaire en Santé Mentale de Québec, Québec, QC, Canada (Dr Kriz); and Département de psychiatrie et neurosciences, Université Laval, Québec, QC, Canada (Drs Kriz and Cicchetti).
Jasna KrizDepartment of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom (Drs Drouin-Ouellet and Barker); Centre de recherche du CHU de Québec, Québec, QC, Canada (Dr St-Amour, Ms Saint-Pierre, Mr Lamontagne-Proulx, and Dr Cicchetti); Centre de Recherche de l'Institut Universitaire en Santé Mentale de Québec, Québec, QC, Canada (Dr Kriz); and Département de psychiatrie et neurosciences, Université Laval, Québec, QC, Canada (Drs Kriz and Cicchetti).
Roger A BarkerDepartment of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom (Drs Drouin-Ouellet and Barker); Centre de recherche du CHU de Québec, Québec, QC, Canada (Dr St-Amour, Ms Saint-Pierre, Mr Lamontagne-Proulx, and Dr Cicchetti); Centre de Recherche de l'Institut Universitaire en Santé Mentale de Québec, Québec, QC, Canada (Dr Kriz); and Département de psychiatrie et neurosciences, Université Laval, Québec, QC, Canada (Drs Kriz and Cicchetti).
Francesca CicchettiDepartment of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom (Drs Drouin-Ouellet and Barker); Centre de recherche du CHU de Québec, Québec, QC, Canada (Dr St-Amour, Ms Saint-Pierre, Mr Lamontagne-Proulx, and Dr Cicchetti); Centre de Recherche de l'Institut Universitaire en Santé Mentale de Québec, Québec, QC, Canada (Dr Kriz); and Département de psychiatrie et neurosciences, Université Laval, Québec, QC, Canada (Drs Kriz and Cicchetti). jd628@cam.ac.uk francesca.cicchetti@crchudequebec.ulaval.ca.
Institut Universitaire en Santé Mentale de Québec · CAHôpital du Saint-Sacrement · CAUniversity of Cambridge · GB

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

backgroundAccumulating evidence supports a role for the immune system in the pathogenesis of Parkinson's disease. Importantly, recent preclinical studies are now suggesting a specific contribution of inflammation to the α-synuclein-induced pathology seen in this condition.

methodsWe used flow cytometry and western blots to detect toll-like receptor 2 and 4 expression in blood and brain samples of Parkinson's disease patients and mice overexpressing human α-synuclein. To further assess the effects of α-synuclein overexpression on the innate immune system, we performed a longitudinal study using Thy1.2-α-synuclein mice that expressed a bicistronic DNA construct (reporter genes luciferase and green fluorescent protein) under the transcriptional control of the murine toll-like receptor 2 promoter.

resultsHere, we report increases in toll-like receptors 2 and 4 expression in circulating monocytes and of toll-like receptor 4 in B cells and in the caudate/putamen of Parkinson's disease patients. Monthly bioluminescence imaging of Thy1.2-α-synuclein mice showed increasing toll-like receptor 2 expression from 10 months of age, although no change in toll-like receptor 2 and 4 expression was observed in the blood and brain of these mice at 12 months of age. Dexamethasone treatment starting at 5 months of age for 1 month significantly decreased the microglial response in the brain of these mice and promoted functional recovery as observed using a wheel-running activity test.

conclusionOur results show that toll-like receptors 2 and 4 are modulated in the blood and brain of Parkinson's disease patients and that overexpression of α-synuclein leads to a progressive microglial response, the inhibition of which has a beneficial impact on some motor phenotypes of an animal model of α-synucleinopathy.

Indexed as

AgedAged, 80 and overalpha-SynucleinAnimalsAntiparkinson AgentsB-LymphocytesBrainCase-Control StudiesDexamethasoneDisease Models, AnimalFemaleGreen Fluorescent ProteinsHumansMaleMice, Inbred C57BLMice, Transgenicalpha-SynucleinAntiparkinson AgentsDexamethasoneGreen Fluorescent ProteinsSNCA protein, humanTLR2 protein, humanTlr2 protein, mouseTLR4 protein, humanTlr4 protein, mouseToll-Like Receptor 2Toll-Like Receptor 4Toll-Like Receptorsbioluminescence imagingdexamethasonemicrogliaTLR2TLR4α-synuclein

Identifiers

PMID25522431
PMCPMC4438545
OpenAlexW2114037757

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.