Evidence map›Paper›PMID 32243088›Full record

ArticleAnnals of clinical and translational neurology2020

Reduced neurosteroid potentiation of GABA

Suchitra Joshi, William H Roden, Jaideep Kapur, Laura A Jansen

Open access · goldAbstract read
In one paragraph

Article in Annals of clinical and translational neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 11% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. Cys-loop receptors on cannabinoids: All high?Frontiers in physiology · 2022
    Pooled it
  2. Review
  3. Review
  4. Article
  5. Virally-induced expression of GABAProgress in neurobiology · 2022
    Article
  6. Article
  7. Article
  8. Review
  9. Increased expression of GABABrain communications · 2021
    Article
  10. Neurosteroids and Focal Epileptic Disorders.International journal of molecular sciences · 2020
    Review
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

4 authors at 2 institutions in 1 country.

Suchitra JoshiDepartment of Neurology, University of Virginia, Charlottesville, Virginia.ORCID 0000-0003-3524-2061
William H RodenSeattle Children's Research Institute, Seattle, Washington.
Jaideep KapurDepartment of Neurology, University of Virginia, Charlottesville, Virginia.ORCID 0000-0002-8608-1352
Laura A JansenDepartment of Neurology, University of Virginia, Charlottesville, Virginia.
University of Virginia · USWashington University in St. Louis · US

Funding

TREATMENT OF STATUS EPILEPTICUSR01NS040337 · NINDS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI KAPUR, JAIDEEP · 2000 to 2021
$5.0M
Neurosteroid Regulation of SeizuresR01NS044370 · NINDS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI KAPUR, JAIDEEP · 2003 to 2017
$4.1M
Age-Dependent Dysfunction of GABAergic Neurotransmission Due to Autism-Associated mTOR Pathway ActivationR01MH110448 · NIMH · WASHINGTON UNIVERSITY · PI JANSEN, LAURA A, WONG, MICHAEL · 2017 to 2021
$2.0M
Progesterone receptor regulation of seizuresR01NS110863 · NINDS · UNIVERSITY OF VIRGINIA · PI JOSHI, SUCHITRA · 2019 to 2023
$1.8M
Early-Life Seizures and Development of GABAergic Inhibition in the Human BrainK02NS072162 · NINDS · UNIVERSITY OF VIRGINIA · PI JANSEN, LAURA A · 2011 to 2013
$581k
NIMH NIH HHS R01 MH110448NINDS NIH HHS K02 NS072162NINDS NIH HHS R01 NS040337NINDS NIH HHS R01 NS044370NINDS NIH HHS R01 NS110863
6 · The paper itself

Abstract

objectiveNeurosteroids regulate neuronal excitability by potentiating γ-aminobutyric acid type-A receptors (GABARs). In animal models of temporal lobe epilepsy, the neurosteroid sensitivity of GABARs is diminished and GABAR subunit composition is altered. We tested whether similar changes occur in patients with epilepsy and if depolarization-induced increases in neuronal activity can replicate this effect.

methodsWe determined GABAR α4 subunit expression in cortical tissue resected from pediatric epilepsy patients. Modulation of human GABARs by allopregnanolone and Ro15-4513 was measured in Xenopus oocytes using whole-cell patch clamp. To extend the findings obtained using tissue from epilepsy patients, we evaluated GABAR expression and modulation by allopregnanolone and Ro15-4513 in cultured rat hippocampal neurons exposed to high extracellular potassium (HK) to increase neuronal activity.

resultsExpression of α4 subunits was increased in pediatric cortical epilepsy specimens encompassing multiple pathologies. The potentiation of GABA-evoked currents by the neurosteroid allopregnanolone was decreased in Xenopus oocytes expressing GABARs isolated from epilepsy patients. Furthermore, receptors isolated from epilepsy but not control tissue were sensitive to potentiation by Ro15-4513, indicating higher expression of α

interpretationThese findings suggest that seizure activity-induced upregulation of α

Indexed as

AdolescentAdultAnimalsAzidesBenzodiazepinesCells, CulturedCerebral CortexChildChild, PreschoolDrug Resistant EpilepsyElectrophysiological PhenomenaFemaleGABA-A Receptor AgonistsHippocampusHumansInfantAzidesBenzodiazepinesGABA-A Receptor AgonistsGABRA4 protein, humanNeurosteroidsPregnanoloneReceptors, GABA-ARo 15-4513

Identifiers

PMID32243088
PMCPMC7187710
OpenAlexW3014677086

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.