Evidence map›Paper›PMID 31874200›Full record

ArticleBrain, behavior, and immunity2020

A silent agonist of α7 nicotinic acetylcholine receptors modulates inflammation ex vivo and attenuates EAE.

Jean-Rémi Godin, Patrick Roy, Marta Quadri, Deniz Bagdas, Wisam Toma, Ramya Narendrula-Kotha, Osama A Kishta, M Imad Damaj, Nicole A Horenstein, Roger L Papke and 1 more

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

Article in Brain, behavior, and immunity, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.6field-weighted citation impact, top 9% 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

27 citing papers in PubMed, 50 citations in OpenAlex.

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  6. Electrical stimulation of the vagus nerve ameliorates inflammation and disease activity in a rat EAE model of multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2024
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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

11 authors at 4 institutions in 2 countries.

Jean-Rémi GodinDépartement de Chimie et Biochimie, Université de Moncton, Moncton, NB, Canada.
Patrick RoyDépartement de Chimie et Biochimie, Université de Moncton, Moncton, NB, Canada.
Marta QuadriDepartment of Pharmacology and Therapeutics, University of Florida, PO Box 100267, Gainesville, FL, USA; Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL, USA.
Deniz BagdasDepartment of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA.
Wisam TomaDepartment of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA.
Ramya Narendrula-KothaNorthern Ontario School of Medicine, Sudbury, ON, Canada.
Osama A KishtaNorthern Ontario School of Medicine, Sudbury, ON, Canada.
M Imad DamajDepartment of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA.
Nicole A HorensteinDepartment of Pharmacology and Therapeutics, University of Florida, PO Box 100267, Gainesville, FL, USA.
Roger L PapkeDepartment of Chemistry, University of Florida, PO Box 117200, Gainesville, FL, USA.
Alain R SimardDépartement de Chimie et Biochimie, Université de Moncton, Moncton, NB, Canada; Northern Ontario School of Medicine, Sudbury, ON, Canada; Department of Chemistry and Biochemistry, Laurentian University, Sudbury, ON, Canada; Department of Biology, Laurentian University, Sudbury, ON, Canada. Electronic address: asimard@nosm.ca.
Université de Moncton · CAUniversity of Florida · USVirginia Commonwealth University Medical Center · USNOSM University · CA

Funding

Targeting of Alpha7 nAChR for therapeutic effectsR01GM057481 · NIGMS · UNIVERSITY OF FLORIDA · PI PAPKE, ROGER L · 2000 to 2023
$7.6M
NIGMS NIH HHS R01 GM057481
6 · The paper itself

Abstract

Nicotinic acetylcholine receptors (nAChRs) are best known to function as ligand-gated ion channels in the nervous system. However, recent evidence suggests that nicotine modulates inflammation by desensitizing non-neuronal nAChRs, rather than by inducing channel opening. Silent agonists are molecules that selectively induce the desensitized state of nAChRs while producing little or no channel opening. A silent agonist of α7 nAChRs has recently been shown to reduce inflammation in an animal model of inflammatory pain. The objective of this study was to determine whether a silent agonist of α7 nAChRs can also effectively modulate inflammation and disease manifestation in an animal model of multiple sclerosis. We first evaluated the effects of various nAChR ligands and of an α7 nAChR-selective silent agonist, 1-ethyl-4-(3-(bromo)phenyl)piperazine (m-bromo PEP), on the modulation of mouse bone marrow-derived monocyte/macrophage (BMDM) numbers, phenotype and cytokine production. The non-competitive antagonist mecamylamine and the silent agonist m-bromo PEP reduced pro-inflammatory BMDM numbers by affecting their viability and proliferation. Both molecules also significantly reduced cytokine production by mouse BMDMs and significantly ameliorated disease in experimental autoimmune encephalomyelitis. Finally, m-bromo PEP also reduced chronic inflammatory pain in mice. Taken together, our results further support the hypothesis that nAChRs may modulate inflammation via receptor desensitization rather than channel opening. α7 nAChR-selective silent agonists may thus be a novel source of anti-inflammatory compounds that could be used for the treatment of inflammatory disorders.

Indexed as

Encephalomyelitis, Autoimmune, ExperimentalReceptors, Nicotinicalpha7 Nicotinic Acetylcholine ReceptorAnimalsInflammationMiceNicotinic Agonistsalpha7 Nicotinic Acetylcholine ReceptorNicotinic AgonistsReceptors, NicotinicCNS inflammationCytokinesExperimental autoimmune encephalomyelitisInflammationInflammatory painNicotinic acetylcholine receptorsSilent agonism

Identifiers

PMID31874200
PMCPMC7604877
OpenAlexW2998707963

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.