Evidence map›Paper›PMID 35579153›Full record

ArticleCurrent neuropharmacology2023

mGlu3 Metabotropic Glutamate Receptors as a Target for the Treatment of Absence Epilepsy: Preclinical and Human Genetics Data.

Roberta Celli, Pasquale Striano, Rita Citraro, Luisa Di Menna, Milena Cannella, Tiziana Imbriglio, Mahmoud Koko, Giovambattista De Sarro, James A Monn, Giuseppe Battaglia and 43 more

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

Article in Current neuropharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.8field-weighted citation impact, top 34% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
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

53 authors at 6 institutions in 3 countries.

Roberta CelliI.R.C.C.S. Neuromed, Pozzilli, Italy.
Pasquale StrianoDepartment Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova, Italy.
Rita CitraroUniversity of Catanzaro, School of Medicine, Science of Health Department, FAS@UMG Research Center, Catanzaro, Italy.
Luisa Di MennaI.R.C.C.S. Neuromed, Pozzilli, Italy.
Milena CannellaI.R.C.C.S. Neuromed, Pozzilli, Italy.
Tiziana ImbriglioI.R.C.C.S. Neuromed, Pozzilli, Italy.
Mahmoud KokoDepartment of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.
Giovambattista De SarroUniversity of Catanzaro, School of Medicine, Science of Health Department, FAS@UMG Research Center, Catanzaro, Italy.
James A MonnI.R.C.C.S. Neuromed, Pozzilli, Italy.
Giuseppe BattagliaI.R.C.C.S. Neuromed, Pozzilli, Italy.
Gilles Van LuijtelaarDonders Center for Cognition, Radboud University, Nijmegen, the Netherlands.
Ferdinando NicolettiI.R.C.C.S. Neuromed, Pozzilli, Italy.
Emilio RussoUniversity of Catanzaro, School of Medicine, Science of Health Department, FAS@UMG Research Center, Catanzaro, Italy.
Antonio LeoUniversity of Catanzaro, School of Medicine, Science of Health Department, FAS@UMG Research Center, Catanzaro, Italy.
EuroEPINOMICS CoGIE Consortium
Aarno PalotieWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom
Anna-Elina Lehesjoki Folkhalsan, Institute of Genetics, Helsinki, Finland; Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland; Neuroscience Center, University of Helsinki, Helsinki, Finland
Ann-Kathrin RuppertCologne Center for Genomics, University of Cologne, Cologne, Germany
Auli SirenOutpatient Clinic for Persons with Intellectual Disability, Tampere University Hospital, Tampere, Finland
Bobby KoelemanDepartment of Medical Genetics, Division of Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
Dennis LalCologne Center for Genomics, University of Cologne, Cologne, Germany
Felicitas BeckerDepartment of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tubingen, Tubingen, Germany
Hande CaglayanDepartment of Molecular Biology and Genetics, Bogazici University, Istanbul, Turkey
Helle HjalgrimDanish Epilepsy Centre, Dianalund, Denmark Institute for Regional Health Services, University of Southern Denmark, Odense, Denmark
Hiltrud MuhleUniversity Medical Center Schleswig-Holstein, Christian-Albrechts University, Kiel, Germany
Holger ThieleCologne Center for Genomics, University of Cologne, Cologne, Germany
Ingo HelbigUniversity Medical Center Schleswig-Holstein, Christian-Albrechts University, Kiel, Germany
Janine AltmullerCologne Center for Genomics, University of Cologne, Cologne, Germany
Kamel JabbariCologne Center for Genomics, University of Cologne, Cologne, Germany
Kate EverettHuman Genetics Research Centre, St. George's University of London, London, United Kingdom
Patrick MayLuxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
Peter NürnbergCologne Center for Genomics, University of Cologne, Cologne, Germany
Rikke MøllerDanish Epilepsy Centre, Dianalund, Denmark; Institute for Regional Health Services, University of Southern Denmark, Odense, Denmark
Rima NabboutCentre de Reference Epilepsies Rares, Inserm U1129, Neuropediatrics Department, Necker-Enfants Malades Hospital, APHP, Paris Descartes University, CEA, Orsay, France
Federico ZaraIRCCS G. Gaslini and University of Genova, Genova, Italy
Marcello ScalaIRCCS G. Gaslini and University of Genova, Genova, Italy
Michele IacominoIRCCS G. Gaslini and University of Genova, Genova, Italy
Paolo ScudieriIRCCS G. Gaslini and University of Genova, Genova, Italy
Renata BocciardiIRCCS G. Gaslini and University of Genova, Genova, Italy
Ganna BalaguraIRCCS G. Gaslini and University of Genova, Genova, Italy
Carlo MinettiIRCCS G. Gaslini and University of Genova, Genova, Italy
Antonella RivaIRCCS G. Gaslini and University of Genova, Genova, Italy
Maria Stella VariIRCCS G. Gaslini and University of Genova, Genova, Italy
Elisabetta AmadoriIRCCS G. Gaslini and University of Genova, Genova, Italy
Martina PerinelliIRCCS G. Gaslini and University of Genova, Genova, Italy
Alberto VerrottiDepartment of Pediatrics, University of Perugia, Perugia, Italy
Roland KrauseLuxembourg Center for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
Rudi BallingLuxembourg Center for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
Stephanie BaulacInstitut National de la Santé et de la Recherche Médicale U975, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinie`re, Hospital Pitié-Salpêtrière, Paris, France
Thomas SanderCologne Center for Genomics, University of Cologne, Cologne, Germany
Wolfram KunzDepartment of Epileptology and Life & Brain Center, University of Bonn Medical Center, Bonn, Germany
Holger LercheDepartment of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tubingen, Tubingen, Germany
Yvonne WeberDepartment of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tubingen, Tubingen, Germany
Istituto Neurologico Mediterraneo · ITMagna Graecia University · ITSapienza University of Rome · ITHertie Institute for Clinical Brain Research · DEIstituto Giannina Gaslini · ITRadboud University Nijmegen · NL

Funding

Italian Ministry of Health Ricerca Corrente 855/2020-PR, 320/2019-PR, 163/2018
6 · The paper itself

Abstract

backgroundPrevious studies suggest that different metabotropic glutamate (mGlu) receptor subtypes are potential drug targets for treating absence epilepsy. However, no information is available on mGlu3 receptors.

objectiveTo examine whether (i) changes of mGlu3 receptor expression/signaling are found in the somatosensory cortex and thalamus of WAG/Rij rats developing spontaneous absence seizures; (ii) selective activation of mGlu3 receptors with LY2794193 affects the number and duration of spikewave discharges (SWDs) in WAG/Rij rats; and (iii) a genetic variant of GRM3 (encoding the mGlu3 receptor) is associated with absence epilepsy.

methodsAnimals: immunoblot analysis of mGlu3 receptors, GAT-1, GLAST, and GLT-1; realtime PCR analysis of mGlu3 mRNA levels; assessment of mGlu3 receptor signaling; EEG analysis of SWDs; assessment of depressive-like behavior. Humans: search for GRM3 and GRM5 missense variants in 196 patients with absence epilepsy or other Idiopathic Generalized Epilepsy (IGE)/ Genetic Generalized Epilepsy (GGE) and 125,748 controls.

resultsmGlu3 protein levels and mGlu3-mediated inhibition of cAMP formation were reduced in the thalamus and somatosensory cortex of pre-symptomatic (25-27 days old) and symptomatic (6-7 months old) WAG/Rij rats compared to age-matched controls. Treatment with LY2794193 (1 or 10 mg/kg, i.p.) reduced absence seizures and depressive-like behavior in WAG/Rij rats. LY2794193 also enhanced GAT1, GLAST, and GLT-1 protein levels in the thalamus and somatosensory cortex. GRM3 and GRM5 gene variants did not differ between epileptic patients and controls.

conclusionWe suggest that mGlu3 receptors modulate the activity of the cortico-thalamo-cortical circuit underlying SWDs and that selective mGlu3 receptor agonists are promising candidate drugs for absence epilepsy treatment.

Indexed as

Epilepsy, AbsenceReceptors, Metabotropic GlutamateAnimalsDisease Models, AnimalElectroencephalographyHuman GeneticsHumansInfantRatsSeizuresReceptors, Metabotropic GlutamateAbsence epilepsycortico-thalamo-cortical networkEEGGABAglutamatehuman geneticsmGlu3 receptors

Identifiers

PMID35579153
PMCPMC10193767
OpenAlexW4280558744

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.