Evidence map›Paper›PMID 33344696›Full record

ArticleNeurobiology of stress2020

Restoring tripartite glutamatergic synapses: A potential therapy for mood and cognitive deficits in Gulf War illness.

Xueqin Wang, Zan Xu, Fangli Zhao, Kuanhung J Lin, Joshua B Foster, Tianqi Xiao, Nydia Kung, Candice C Askwith, John P Bruno, Valentina Valentini and 2 more

Abstract read
In one paragraph

Article in Neurobiology of stress, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
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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.

Xueqin WangDepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USA.
Zan XuDepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USA.
Fangli ZhaoDepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USA.
Kuanhung J LinDepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USA.
Joshua B FosterDepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USA.
Tianqi XiaoDepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USA.
Nydia KungDepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USA.
Candice C AskwithDepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USA.
John P BrunoDepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USA.
Valentina ValentiniDepartment of Psychology, College of Arts and Sciences, The Ohio State University, Columbus, OH, USA.
Kevin J HodgettsDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA.
Chien-Liang Glenn LinDepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USA.

Funding

Ohio State Neuroscience Centr CoreP30NS045758 · NINDS · OHIO STATE UNIVERSITY · PI MCTIGUE, DANA M · 2004 to 2015
$7.7M
Ohio State University Neuroscience Center Core-Core EP30NS104177 · NINDS · OHIO STATE UNIVERSITY · PI BROWN, ANTHONY · 2017 to 2020
$1.9M
NINDS NIH HHS P30 NS045758NINDS NIH HHS P30 NS104177
6 · The paper itself

Abstract

Gulf War illness is associated with a combination of exposure to war-related chemical agents and traumatic stress. Currently, there are no effective treatments, and the pathophysiology remains elusive. Neurological problems are among the most commonly reported symptoms. In this study, we investigated the glutamatergic system in the hippocampi of mice exposed to war-related chemical agents and stress. Mice developed Gulf War illness-like symptoms, including mood deficits, cognitive impairments, and fatigue. They exhibited the following pathological changes in hippocampi: elevated extracellular glutamate levels, impaired glutamatergic synapses, astrocyte atrophy, loss of interneurons, and decreased neurogenesis. LDN/OSU-215111 is a small-molecule that can strengthen the structure and function of both the astrocytic processes and the glutamatergic synapses that together form the tripartite synapses. We found that LDN/OSU-215111 effectively prevented the development of mood and cognitive deficits in mice when treatment was implemented immediately following the exposure. Moreover, when symptoms were already present, LDN/OSU-215111 still significantly ameliorated these deficits; impressively, benefits were sustained one month after treatment cessation, indicating disease modification. LDN/OSU-215111 effectively normalized hippocampal pathological changes. Overall, this study provides strong evidence that restoration of tripartite glutamatergic synapses by LDN/OSU-215111 is a potential therapy for Gulf War illness.

Indexed as

BBB, Blood brain barrierCA, Cornu ammonisDCX, DoublecortinDEET, N, N-Diethyl-meta-toluamideDG, Dentate gyrusEAAT2, Excitatory amino acid transporter 2fEPSP, field excitatory postsynaptic potentialsGABA, γ-aminobutyric acidGFAP, glial fibrillary acidic proteinGulf war illnessGWI, gulf war illnessLTP, Long term potentiationMood deficits and cognitive impairmentsPB, Pyridostigmine bromidePSD95, Postsynaptic density protein 95PV, ParvalbuminsEPSC/mEPSC, Spontaneous/miniature excitatory postsynaptic currentsIPSC/mIPSC, Spontaneous/miniature inhibitory postsynaptic currentTBS, Theta burst stimulationTherapyTraumatic stressTripartite glutamatergic synapsesvGAT, Vesicular inhibitory amino acid transportervGLUT1, Vesicular glutamate transporter 1

Identifiers

PMID33344696
PMCPMC7739039

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.