Evidence map›Paper›PMID 34801513›Full record

ArticleLife sciences2022

Induction of distinct neuroinflammatory markers and gut dysbiosis by differential pyridostigmine bromide dosing in a chronic mouse model of GWI showing persistent exercise fatigue and cognitive impairment.

Elena V Kozlova, Bruno Carabelli, Anthony E Bishay, Rui Liu, Maximillian E Denys, John C Macbeth, Varadh Piamthai, Meli'sa S Crawford, Declan F McCole, Nicole I Zur Nieden and 2 more

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

Article in Life sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
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  5. Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024
    Review
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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

12 authors at 1 institution in 1 country.

Elena V KozlovaDepartment of Molecular, Cell and Systems Biology, University of California, Riverside, CA, USA; Neuroscience Graduate Program, University of California, Riverside, CA, USA.
Bruno CarabelliDepartment of Molecular, Cell and Systems Biology, University of California, Riverside, CA, USA.
Anthony E BishayDepartment of Molecular, Cell and Systems Biology, University of California, Riverside, CA, USA.
Rui LiuDepartment of Microbiology and Plant Pathology, University of California, Riverside, CA, USA; Graduate Program in Genetics, Genomics, and Bioinformatics, University of California, Riverside, CA, USA.
Maximillian E DenysDepartment of Molecular, Cell and Systems Biology, University of California, Riverside, CA, USA.
John C MacbethDepartment of Microbiology and Plant Pathology, University of California, Riverside, CA, USA; Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA.
Varadh PiamthaiDepartment of Microbiology and Plant Pathology, University of California, Riverside, CA, USA.
Meli'sa S CrawfordDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA.
Declan F McColeDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA.
Nicole I Zur NiedenDepartment of Molecular, Cell and Systems Biology, University of California, Riverside, CA, USA.
Ansel HsiaoDepartment of Microbiology and Plant Pathology, University of California, Riverside, CA, USA.
Margarita C Curras-CollazoDepartment of Molecular, Cell and Systems Biology, University of California, Riverside, CA, USA. Electronic address: mcur@ucr.edu.
University of California, Riverside · US

Funding

A NOVEL ROLE FOR PTPN2 IN INTESTINAL EPITHELIAL BARRIER REGULATIONR01DK091281 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Declan McCole · 2012 to 2026
$5.5M
Vibrio cholerae antinitrosative stress defenses and gut microbiome interactionR01AI157106 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HSIAO, ANSEL, ZHU, JUN · 2020 to 2024
$4.0M
Tyrosine Phosphatase Regulation of Mucosal Macrophage-Epithelial Cell Cross-talkR01AI153314 · NIAID · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI MCCOLE, DECLAN · 2020 to 2024
$2.5M
Gut microbiome-mediated small-molecule signaling and resistance to invading microorganismsR35GM124724 · NIGMS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI HSIAO, ANSEL · 2017 to 2021
$1.8M
Mechanistic Characterization of the IBD Risk Gene, PTPN2, as a Novel Susceptibility Marker for Increased SARS-CoV-2 InfectionR01DK130373 · NIDDK · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI MCCOLE, DECLAN · 2021 to 2023
$1.1M
Inflammatory Bowel Disease Susceptibility Gene Regulation of AnemiaR21AI152017 · NIAID · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI MCCOLE, DECLAN · 2021 to 2022
$428k
NIAID NIH HHS R01 AI153314NIAID NIH HHS R01 AI157106NIAID NIH HHS R21 AI152017NIDDK NIH HHS R01 DK091281NIDDK NIH HHS R01 DK130373NIGMS NIH HHS R35 GM124724
6 · The paper itself

Abstract

aimsTo characterize neuroinflammatory and gut dysbiosis signatures that accompany exaggerated exercise fatigue and cognitive/mood deficits in a mouse model of Gulf War Illness (GWI).

methodsAdult male C57Bl/6N mice were exposed for 28 d (5 d/wk) to pyridostigmine bromide (P.O.) at 6.5 mg/kg/d, b.i.d. (GW1) or 8.7 mg/kg/d, q.d. (GW2); topical permethrin (1.3 mg/kg), topical N,N-diethyl-meta-toluamide (33%) and restraint stress (5 min). Animals were phenotypically evaluated as described in an accompanying article [124] and sacrificed at 6.6 months post-treatment (PT) to allow measurement of brain neuroinflammation/neuropathic pain gene expression, hippocampal glial fibrillary acidic protein, brain Interleukin-6, gut dysbiosis and serum endotoxin. KEY

findingsCompared to GW1, GW2 showed a more intense neuroinflammatory transcriptional signature relative to sham stress controls. Interleukin-6 was elevated in GW2 and astrogliosis in hippocampal CA1 was seen in both GW groups. Beta-diversity PCoA using weighted Unifrac revealed that gut microbial communities changed after exposure to GW2 at PT188. Both GW1 and GW2 displayed systemic endotoxemia, suggesting a gut-brain mechanism underlies the neuropathological signatures. Using germ-free mice, probiotic supplementation with Lactobacillus reuteri produced less gut permeability than microbiota transplantation using GW2 feces. SIGNIFICANCE: Our findings demonstrate that GW agents dose-dependently induce differential neuropathology and gut dysbiosis associated with cognitive, exercise fatigue and mood GWI phenotypes. Establishment of a comprehensive animal model that recapitulates multiple GWI symptom domains and neuroinflammation has significant implications for uncovering pathophysiology, improving diagnosis and treatment for GWI.

Indexed as

Gastrointestinal MicrobiomePhysical Conditioning, AnimalAnimalsBiomarkersCholinesterase InhibitorsCognitive DysfunctionDisease Models, AnimalDose-Response Relationship, DrugDysbiosisEndotoxemiaFatigueGene Expression ProfilingGene Expression RegulationGliosisMaleMiceBiomarkersCholinesterase InhibitorsPyridostigmine BromideCentral nervous systemEndotoxemiaGut-brain axisGut microbiomeInterleukinsIntestinal permeabilityProbioticToxic wounds

Identifiers

PMID34801513
PMCPMC9048156
OpenAlexW3217129377

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.