Evidence map›Paper›PMID 30189284›Full record

ArticleJournal of neuroscience methods2018

A Caenorhabditis elegans assay of seizure-like activity optimised for identifying antiepileptic drugs and their mechanisms of action.

Shi Quan Wong, Alistair Jones, Steven Dodd, Douglas Grimes, Jeff W Barclay, Anthony G Marson, Vincent T Cunliffe, Robert D Burgoyne, Graeme J Sills, Alan Morgan

Open access · hybridAbstract read
In one paragraph

Article in Journal of neuroscience methods, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.8field-weighted citation impact, top 35% 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

18 citing papers in PubMed, 24 citations in OpenAlex.

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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

10 authors at 2 institutions in 1 country.

Shi Quan WongDepartment of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. Electronic address: wongsq@liverpool.ac.uk.
Alistair JonesDepartment of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. Electronic address: Alistair.Jones@liverpool.ac.uk.
Steven DoddDepartment of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. Electronic address: stedodd@liverpool.ac.uk.
Douglas GrimesDepartment of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. Electronic address: hldgrime@liverpool.ac.uk.
Jeff W BarclayDepartment of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. Electronic address: barclayj@liverpool.ac.uk.
Anthony G MarsonDepartment of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. Electronic address: marjon01@liverpool.ac.uk.
Vincent T CunliffeDepartment of Biomedical Science, University of Sheffield, Sheffield, UK. Electronic address: v.t.cunliffe@sheffield.ac.uk.
Robert D BurgoyneDepartment of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. Electronic address: burgoyne@liverpool.ac.uk.
Graeme J SillsDepartment of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. Electronic address: g.sills@liverpool.ac.uk.
Alan MorganDepartment of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. Electronic address: amorgan@liverpool.ac.uk.
University of Liverpool · GBSheffield Children's University · GB

Funding

Medical Research Council MC_PC_13076Wellcome TrustWellcome Trust 102378/Z/13
6 · The paper itself

Abstract

backgroundEpilepsy affects around 1% of people, but existing antiepileptic drugs (AEDs) only offer symptomatic relief and are ineffective in approximately 30% of patients. Hence, new AEDs are sorely needed. However, a major bottleneck is the low-throughput nature of early-stage AED screens in conventional rodent models. This process could potentially be expedited by using simpler invertebrate systems, such as the nematode Caenorhabditis elegans. NEW

methodHead-bobbing convulsions were previously reported to be inducible by pentylenetetrazol (PTZ) in C. elegans with loss-of-function mutations in unc-49, which encodes a GABA

resultsConvulsions induced within minutes of PTZ exposure in unc-49 mutants were strongly inhibited by the established AED ethosuximide. This protective activity was independent of ethosuximide's suggested target, the T-type calcium channel, as a null mutation in the worm cca-1 ortholog did not affect ethosuximide's anticonvulsant action. COMPARISON WITH EXISTING

methodOur streamlined assay is AED-validated, feasible for higher throughput compound screens, and can facilitate insights into AED mechanisms of action.

conclusionsBased on an epilepsy-associated genetic background, this C. elegans unc-49 model of seizure-like activity presents an ethical, higher throughput alternative to conventional rodent seizure models for initial AED screens.

Indexed as

Disease Models, AnimalAnimalsAnticonvulsantsCaenorhabditis elegansCaenorhabditis elegans ProteinsConvulsantsDrug Evaluation, PreclinicalEthosuximidePentylenetetrazoleReceptors, GABA-ASeizuresAnticonvulsantsCaenorhabditis elegans ProteinsConvulsantsEthosuximidePentylenetetrazoleReceptors, GABA-AUnc-49 protein, C elegansAnticonvulsantCaenorhabditis elegansCalcium channelDrug screensEpilepsyEthosuximideGABA receptorPentylenetetrazol

Identifiers

PMID30189284
PMCPMC6200019
OpenAlexW2890216918

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.