Evidence map›Paper›PMID 25081057›Full record

ArticleNature communications2014

Selective suppression of excessive GluN2C expression rescues early epilepsy in a tuberous sclerosis murine model.

N Lozovaya, S Gataullina, T Tsintsadze, V Tsintsadze, E Pallesi-Pocachard, M Minlebaev, N A Goriounova, E Buhler, F Watrin, S Shityakov and 12 more

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

Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
6.4field-weighted citation impact, top 3% 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

61 citing papers in PubMed, 120 citations in OpenAlex.

  1. Trial
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  10. Observational
  11. Epilepsy in Patients with Gliomas.Neurologia medico-chirurgica · 2024
    Review
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  13. Review
  14. Article
  15. Article
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1 more citing papers are in PubMed but not listed here.

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

22 authors at 9 institutions in 3 countries.

N Lozovaya1] INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163, route de Luminy-BP 13, 13273 Marseille Cedex 09, France [2] UMR901, Aix-Marseille University, 58 Boulevard Charles Livon, 13284 Marseille, France [3] INSERM U1129; University Paris Descartes, CEA, Gif sur Yvette, 149 Rue de Sèvres, 75015 Paris, France [4].
S Gataullina1] INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163, route de Luminy-BP 13, 13273 Marseille Cedex 09, France [2] UMR901, Aix-Marseille University, 58 Boulevard Charles Livon, 13284 Marseille, France [3] INSERM U1129; University Paris Descartes, CEA, Gif sur Yvette, 149 Rue de Sèvres, 75015 Paris, France [4].
T Tsintsadze1] INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163, route de Luminy-BP 13, 13273 Marseille Cedex 09, France [2] UMR901, Aix-Marseille University, 58 Boulevard Charles Livon, 13284 Marseille, France [3].
V Tsintsadze1] INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163, route de Luminy-BP 13, 13273 Marseille Cedex 09, France [2] UMR901, Aix-Marseille University, 58 Boulevard Charles Livon, 13284 Marseille, France.
E Pallesi-Pocachard1] INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163, route de Luminy-BP 13, 13273 Marseille Cedex 09, France [2] UMR901, Aix-Marseille University, 58 Boulevard Charles Livon, 13284 Marseille, France.
M Minlebaev1] INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163, route de Luminy-BP 13, 13273 Marseille Cedex 09, France [2] UMR901, Aix-Marseille University, 58 Boulevard Charles Livon, 13284 Marseille, France [3] Laboratory of Neurobiology, Kazan Federal University, Kremlevskaya street 18, 420000 Kazan, Russia.
N A Goriounova1] INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163, route de Luminy-BP 13, 13273 Marseille Cedex 09, France [2] UMR901, Aix-Marseille University, 58 Boulevard Charles Livon, 13284 Marseille, France.
E Buhler1] INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163, route de Luminy-BP 13, 13273 Marseille Cedex 09, France [2] UMR901, Aix-Marseille University, 58 Boulevard Charles Livon, 13284 Marseille, France.
F Watrin1] INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163, route de Luminy-BP 13, 13273 Marseille Cedex 09, France [2] UMR901, Aix-Marseille University, 58 Boulevard Charles Livon, 13284 Marseille, France.
S ShityakovDepartment of Anaesthesia and Critical Care, University of Würzburg, Josef-Schneider-Street 2, 97080 Würzburg, Germany.
A J BeckerDepartment of Neuropathology, University of Bonn Medical Center, Sigmund Freud Street 25, D-53105 Bonn, Germany.
A BordeyNeurosurgery, and Cellular and Molecular Physiology Departments, Yale University School of Medicine, PO Box 208082, New Haven, Connecticut 06520-8082, USA.
M MilhAPHM, Department of Pediatric Neurosurgery and Neurology, CHU Timone, 264 Rue Saint-Pierre, 13385 Marseille Cedex 5, France.
D ScavardaAPHM, Department of Pediatric Neurosurgery and Neurology, CHU Timone, 264 Rue Saint-Pierre, 13385 Marseille Cedex 5, France.
C Bulteau1] INSERM U1129; University Paris Descartes, CEA, Gif sur Yvette, 149 Rue de Sèvres, 75015 Paris, France [2] Department of Pediatric Neurosurgery, Foundation Rothschild, 29 Rue Manin, 75019 Paris, France.
G Dorfmuller1] INSERM U1129; University Paris Descartes, CEA, Gif sur Yvette, 149 Rue de Sèvres, 75015 Paris, France [2] Department of Pediatric Neurosurgery, Foundation Rothschild, 29 Rue Manin, 75019 Paris, France.
O DelalandeDepartment of Pediatric Neurosurgery, Foundation Rothschild, 29 Rue Manin, 75019 Paris, France.
A Represa1] INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163, route de Luminy-BP 13, 13273 Marseille Cedex 09, France [2] UMR901, Aix-Marseille University, 58 Boulevard Charles Livon, 13284 Marseille, France.
C Cardoso1] INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163, route de Luminy-BP 13, 13273 Marseille Cedex 09, France [2] UMR901, Aix-Marseille University, 58 Boulevard Charles Livon, 13284 Marseille, France.
O Dulac1] INSERM U1129; University Paris Descartes, CEA, Gif sur Yvette, 149 Rue de Sèvres, 75015 Paris, France [2] Department of Pediatric Neurosurgery, Foundation Rothschild, 29 Rue Manin, 75019 Paris, France [3] APHP, Necker Hospital, 149 Rue de Sèvres, 75015 Paris, France.
Y Ben-Ari1] INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163, route de Luminy-BP 13, 13273 Marseille Cedex 09, France [2] UMR901, Aix-Marseille University, 58 Boulevard Charles Livon, 13284 Marseille, France.
N Burnashev1] INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163, route de Luminy-BP 13, 13273 Marseille Cedex 09, France [2] UMR901, Aix-Marseille University, 58 Boulevard Charles Livon, 13284 Marseille, France.
Inserm · FROZ Biosciences (France) · FRAix-Marseille Université · FRHôpital de la Timone · FRDélégation Paris 5 · FRFondation de Rothschild · FRUniversity of Bonn · DEUniversity of Würzburg · DEYale University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tuberous sclerosis complex (TSC), caused by dominant mutations in either TSC1 or TSC2 tumour suppressor genes is characterized by the presence of brain malformations, the cortical tubers that are thought to contribute to the generation of pharmacoresistant epilepsy. Here we report that tuberless heterozygote Tsc1(+/-) mice show functional upregulation of cortical GluN2C-containing N-methyl-D-aspartate receptors (NMDARs) in an mTOR-dependent manner and exhibit recurrent, unprovoked seizures during early postnatal life (<P19). Seizures are generated intracortically in the granular layer of the neocortex. Slow kinetics of aberrant GluN2C-mediated currents in spiny stellate cells promotes excessive temporal integration of persistent NMDAR-mediated recurrent excitation and seizure generation. Accordingly, specific GluN2C/D antagonists block seizures in Tsc1(+/-) mice in vivo and in vitro. Likewise, GluN2C expression is upregulated in TSC human surgical resections, and a GluN2C/D antagonist reduces paroxysmal hyperexcitability. Thus, GluN2C receptor constitutes a promising molecular target to treat epilepsy in TSC patients.

Indexed as

Action PotentialsAnimalsAnticonvulsantsDisease Models, AnimalElectroencephalographyEpilepsyGene Expression RegulationHeterozygoteHumansMaleMiceMice, TransgenicMicrotomyNeocortexPatch-Clamp TechniquesPyrazoles4-(5-(4-bromophenyl)-3-(6-methyl-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoic acidAnticonvulsantsmTOR protein, mouseNR2C NMDA receptorPyrazolesQuinolonesReceptors, N-Methyl-D-AspartateTOR Serine-Threonine KinasesTSC1 protein, humanTsc1 protein, mouseTuberous Sclerosis Complex 1 ProteinTumor Suppressor Proteins

Identifiers

PMID25081057
PMCPMC4143949
OpenAlexW2084831913

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

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.