GRK2 and group I mGluR mediate inflammation-induced sensitization to excitotoxic neurodegeneration
Identifieur interne : 001406 ( Ncbi/Curation ); précédent : 001405; suivant : 001407GRK2 and group I mGluR mediate inflammation-induced sensitization to excitotoxic neurodegeneration
Auteurs : Vincent Degos [France, États-Unis] ; Stéphane Peineau [France, Royaume-Uni] ; Cora Nijboer [Pays-Bas] ; Angela M. Kaindl [France] ; Stéphanie Sigaut [France] ; Géraldine Favrais [France] ; Frank Plaisant [France] ; Natacha Teissier [France] ; Elodie Gouadon [France] ; Alain Lombet [France] ; Elie Saliba [France] ; Graham L. Collingridge [Royaume-Uni, Canada, Corée du Sud] ; Mervyn Maze [États-Unis] ; Ferdinando Nicoletti [Italie] ; Cobi Heijnen [Pays-Bas] ; Jean Mantz [France] ; Annemieke Kavelaars [Pays-Bas, États-Unis] ; Pierre Gressens [France, Royaume-Uni]Source :
- Annals of neurology [ 0364-5134 ] ; 2013.
Abstract
The concept of inflammation-induced sensitization is emerging in the field of perinatal brain injury, stroke, Alzheimer disease and multiple sclerosis. However, mechanisms underpinning this process remain unidentified.
We combined
We demonstrate for the first time that group I mGluRs mediate inflammation-induced sensitization to neuronal excitotoxicity in neonatal and adult neurons across species. Inflammation induced G protein–coupled receptor kinase 2 (GRK2) down-regulation and genetic deletion of
Collectively, our findings indicate that inflammation-induced sensitization is universal across species and ages and that group I mGluRs and GRK2 represent new avenues for neuroprotection in perinatal and adult neurological disorders.
Url:
DOI: 10.1002/ana.23868
PubMed: 23494575
PubMed Central: 3837433
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Plessis-Robinson</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A8">Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson</wicri:regionArea><wicri:noRegion>Le Plessis-Robinson</wicri:noRegion><wicri:noRegion>Le Plessis-Robinson</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="A9">Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre</wicri:regionArea><wicri:noRegion>Le Kremlin-Bicêtre</wicri:noRegion><orgName type="university">Université Paris-Sud</orgName><placeName><settlement type="city">Orsay</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Lombet, Alain" sort="Lombet, Alain" 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uniqKey="Saliba E" first="Elie" last="Saliba">Elie Saliba</name><affiliation wicri:level="4"><nlm:aff id="A10">Inserm, U930, Université François Rabelais de Tours, Tours, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, U930, Université François Rabelais de Tours, Tours</wicri:regionArea><placeName><region type="region">Centre-Val de Loire</region><region type="old region">Région Centre</region><settlement type="city">Tours</settlement><settlement type="city">Tours</settlement></placeName><orgName type="university">Université François-Rabelais de Tours</orgName></affiliation></author><author><name sortKey="Collingridge, Graham L" sort="Collingridge, Graham L" uniqKey="Collingridge G" first="Graham L." last="Collingridge">Graham L. Collingridge</name><affiliation wicri:level="1"><nlm:aff id="A5">MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, Medical Sciences Building, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, Medical Sciences Building, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A11">Brain Research Centre, Department of Psychiatry, University of British Columbia, Vancouver, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Brain Research Centre, Department of Psychiatry, University of British Columbia, Vancouver</wicri:regionArea><wicri:noRegion>Vancouver</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="A12">Department of Brain and Cognitive Sciences, Seoul National University, Seoul, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Brain and Cognitive Sciences, Seoul National University, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><settlement type="city">Séoul</settlement></placeName><orgName type="university">Université nationale de Séoul</orgName></affiliation></author><author><name sortKey="Maze, Mervyn" sort="Maze, Mervyn" uniqKey="Maze M" first="Mervyn" last="Maze">Mervyn Maze</name><affiliation wicri:level="3"><nlm:aff id="A4">Department of Anesthesia and Perioperative Care, University of California, San Francisco, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Anesthesia and Perioperative Care, University of California, San Francisco</wicri:regionArea><placeName><settlement type="city">San Francisco</settlement><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Nicoletti, Ferdinando" sort="Nicoletti, Ferdinando" uniqKey="Nicoletti F" first="Ferdinando" last="Nicoletti">Ferdinando Nicoletti</name><affiliation wicri:level="1"><nlm:aff id="A13">Dept. of Physiology and Pharmacology, University of Rome Sapienza, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Dept. of Physiology and Pharmacology, University of Rome Sapienza</wicri:regionArea><wicri:noRegion>University of Rome Sapienza</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A14">IRCCS Neuromed, Pozzilli (IS), Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>IRCCS Neuromed, Pozzilli (IS)</wicri:regionArea><wicri:noRegion>Pozzilli (IS)</wicri:noRegion></affiliation></author><author><name sortKey="Heijnen, Cobi" sort="Heijnen, Cobi" uniqKey="Heijnen C" first="Cobi" last="Heijnen">Cobi Heijnen</name><affiliation wicri:level="3"><nlm:aff id="A6">Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Mantz, Jean" sort="Mantz, Jean" uniqKey="Mantz J" first="Jean" last="Mantz">Jean Mantz</name><affiliation wicri:level="3"><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, U676, Hôpital Robert Debré, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A3">PremUP, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>PremUP, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A15">AP HP, Beaujon Hospital, Department of Anesthesia and Critical Care, Clichy, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>AP HP, Beaujon Hospital, Department of Anesthesia and Critical Care, Clichy</wicri:regionArea><wicri:noRegion>Clichy</wicri:noRegion><wicri:noRegion>Clichy</wicri:noRegion></affiliation></author><author><name sortKey="Kavelaars, Annemieke" sort="Kavelaars, Annemieke" uniqKey="Kavelaars A" first="Annemieke" last="Kavelaars">Annemieke Kavelaars</name><affiliation wicri:level="3"><nlm:aff id="A6">Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A16">Integrative Immunology & Behavior Program, University of Illinois Urbana Champaign, IL, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Integrative Immunology & Behavior Program, University of Illinois Urbana Champaign, IL</wicri:regionArea><wicri:noRegion>IL</wicri:noRegion></affiliation></author><author><name sortKey="Gressens, Pierre" sort="Gressens, Pierre" uniqKey="Gressens P" first="Pierre" last="Gressens">Pierre Gressens</name><affiliation wicri:level="3"><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, U676, Hôpital Robert Debré, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A3">PremUP, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>PremUP, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A17">Centre for the Developing Brain, King's College, St Thomas' Campus, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for the Developing Brain, King's College, St Thomas' Campus, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23494575</idno><idno type="pmc">3837433</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837433</idno><idno type="RBID">PMC:3837433</idno><idno type="doi">10.1002/ana.23868</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000798</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000798</idno><idno type="wicri:Area/Pmc/Curation">000798</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000798</idno><idno type="wicri:Area/Pmc/Checkpoint">000648</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000648</idno><idno type="wicri:Area/Ncbi/Merge">001406</idno><idno type="wicri:Area/Ncbi/Curation">001406</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">GRK2 and group I mGluR mediate inflammation-induced sensitization to excitotoxic neurodegeneration</title><author><name sortKey="Degos, Vincent" sort="Degos, Vincent" uniqKey="Degos V" first="Vincent" last="Degos">Vincent Degos</name><affiliation wicri:level="3"><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, U676, Hôpital Robert Debré, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A3">PremUP, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>PremUP, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A4">Department of Anesthesia and Perioperative Care, University of California, San Francisco, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Anesthesia and Perioperative Care, University of California, San Francisco</wicri:regionArea><placeName><settlement type="city">San Francisco</settlement><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Peineau, Stephane" sort="Peineau, Stephane" uniqKey="Peineau S" first="Stéphane" last="Peineau">Stéphane Peineau</name><affiliation wicri:level="3"><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, U676, Hôpital Robert Debré, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A3">PremUP, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>PremUP, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A5">MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, Medical Sciences Building, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, Medical Sciences Building, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author><author><name sortKey="Nijboer, Cora" sort="Nijboer, Cora" uniqKey="Nijboer C" first="Cora" last="Nijboer">Cora Nijboer</name><affiliation wicri:level="3"><nlm:aff id="A6">Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Kaindl, Angela M" sort="Kaindl, Angela M" uniqKey="Kaindl A" first="Angela M." last="Kaindl">Angela M. Kaindl</name><affiliation wicri:level="3"><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, U676, Hôpital Robert Debré, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A3">PremUP, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>PremUP, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Sigaut, Stephanie" sort="Sigaut, Stephanie" uniqKey="Sigaut S" first="Stéphanie" last="Sigaut">Stéphanie Sigaut</name><affiliation wicri:level="3"><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, U676, Hôpital Robert Debré, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A3">PremUP, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>PremUP, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Favrais, Geraldine" sort="Favrais, Geraldine" uniqKey="Favrais G" first="Géraldine" last="Favrais">Géraldine Favrais</name><affiliation wicri:level="3"><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, U676, Hôpital Robert Debré, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A3">PremUP, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>PremUP, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Plaisant, Frank" sort="Plaisant, Frank" uniqKey="Plaisant F" first="Frank" last="Plaisant">Frank Plaisant</name><affiliation wicri:level="3"><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, U676, Hôpital Robert Debré, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A3">PremUP, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>PremUP, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Teissier, Natacha" sort="Teissier, Natacha" uniqKey="Teissier N" first="Natacha" last="Teissier">Natacha Teissier</name><affiliation wicri:level="3"><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, U676, Hôpital Robert Debré, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A3">PremUP, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>PremUP, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Gouadon, Elodie" sort="Gouadon, Elodie" uniqKey="Gouadon E" first="Elodie" last="Gouadon">Elodie Gouadon</name><affiliation wicri:level="1"><nlm:aff id="A7">Inserm, UMR 999, Labex LERMIT, Le Plessis-Robinson, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, UMR 999, Labex LERMIT, Le Plessis-Robinson</wicri:regionArea><wicri:noRegion>Le Plessis-Robinson</wicri:noRegion><wicri:noRegion>Le Plessis-Robinson</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A8">Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson</wicri:regionArea><wicri:noRegion>Le Plessis-Robinson</wicri:noRegion><wicri:noRegion>Le Plessis-Robinson</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="A9">Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre</wicri:regionArea><wicri:noRegion>Le Kremlin-Bicêtre</wicri:noRegion><orgName type="university">Université Paris-Sud</orgName><placeName><settlement type="city">Orsay</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Lombet, Alain" sort="Lombet, Alain" uniqKey="Lombet A" first="Alain" last="Lombet">Alain Lombet</name><affiliation wicri:level="1"><nlm:aff id="A7">Inserm, UMR 999, Labex LERMIT, Le Plessis-Robinson, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, UMR 999, Labex LERMIT, Le Plessis-Robinson</wicri:regionArea><wicri:noRegion>Le Plessis-Robinson</wicri:noRegion><wicri:noRegion>Le Plessis-Robinson</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="A9">Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre</wicri:regionArea><wicri:noRegion>Le Kremlin-Bicêtre</wicri:noRegion><orgName type="university">Université Paris-Sud</orgName><placeName><settlement type="city">Orsay</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Saliba, Elie" sort="Saliba, Elie" uniqKey="Saliba E" first="Elie" last="Saliba">Elie Saliba</name><affiliation wicri:level="4"><nlm:aff id="A10">Inserm, U930, Université François Rabelais de Tours, Tours, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, U930, Université François Rabelais de Tours, Tours</wicri:regionArea><placeName><region type="region">Centre-Val de Loire</region><region type="old region">Région Centre</region><settlement type="city">Tours</settlement><settlement type="city">Tours</settlement></placeName><orgName type="university">Université François-Rabelais de Tours</orgName></affiliation></author><author><name sortKey="Collingridge, Graham L" sort="Collingridge, Graham L" uniqKey="Collingridge G" first="Graham L." last="Collingridge">Graham L. Collingridge</name><affiliation wicri:level="1"><nlm:aff id="A5">MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, Medical Sciences Building, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, Medical Sciences Building, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A11">Brain Research Centre, Department of Psychiatry, University of British Columbia, Vancouver, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Brain Research Centre, Department of Psychiatry, University of British Columbia, Vancouver</wicri:regionArea><wicri:noRegion>Vancouver</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="A12">Department of Brain and Cognitive Sciences, Seoul National University, Seoul, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Brain and Cognitive Sciences, Seoul National University, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><settlement type="city">Séoul</settlement></placeName><orgName type="university">Université nationale de Séoul</orgName></affiliation></author><author><name sortKey="Maze, Mervyn" sort="Maze, Mervyn" uniqKey="Maze M" first="Mervyn" last="Maze">Mervyn Maze</name><affiliation wicri:level="3"><nlm:aff id="A4">Department of Anesthesia and Perioperative Care, University of California, San Francisco, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Anesthesia and Perioperative Care, University of California, San Francisco</wicri:regionArea><placeName><settlement type="city">San Francisco</settlement><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Nicoletti, Ferdinando" sort="Nicoletti, Ferdinando" uniqKey="Nicoletti F" first="Ferdinando" last="Nicoletti">Ferdinando Nicoletti</name><affiliation wicri:level="1"><nlm:aff id="A13">Dept. of Physiology and Pharmacology, University of Rome Sapienza, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Dept. of Physiology and Pharmacology, University of Rome Sapienza</wicri:regionArea><wicri:noRegion>University of Rome Sapienza</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A14">IRCCS Neuromed, Pozzilli (IS), Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>IRCCS Neuromed, Pozzilli (IS)</wicri:regionArea><wicri:noRegion>Pozzilli (IS)</wicri:noRegion></affiliation></author><author><name sortKey="Heijnen, Cobi" sort="Heijnen, Cobi" uniqKey="Heijnen C" first="Cobi" last="Heijnen">Cobi Heijnen</name><affiliation wicri:level="3"><nlm:aff id="A6">Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Mantz, Jean" sort="Mantz, Jean" uniqKey="Mantz J" first="Jean" last="Mantz">Jean Mantz</name><affiliation wicri:level="3"><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, U676, Hôpital Robert Debré, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A3">PremUP, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>PremUP, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A15">AP HP, Beaujon Hospital, Department of Anesthesia and Critical Care, Clichy, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>AP HP, Beaujon Hospital, Department of Anesthesia and Critical Care, Clichy</wicri:regionArea><wicri:noRegion>Clichy</wicri:noRegion><wicri:noRegion>Clichy</wicri:noRegion></affiliation></author><author><name sortKey="Kavelaars, Annemieke" sort="Kavelaars, Annemieke" uniqKey="Kavelaars A" first="Annemieke" last="Kavelaars">Annemieke Kavelaars</name><affiliation wicri:level="3"><nlm:aff id="A6">Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A16">Integrative Immunology & Behavior Program, University of Illinois Urbana Champaign, IL, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Integrative Immunology & Behavior Program, University of Illinois Urbana Champaign, IL</wicri:regionArea><wicri:noRegion>IL</wicri:noRegion></affiliation></author><author><name sortKey="Gressens, Pierre" sort="Gressens, Pierre" uniqKey="Gressens P" first="Pierre" last="Gressens">Pierre Gressens</name><affiliation wicri:level="3"><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, U676, Hôpital Robert Debré, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A3">PremUP, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>PremUP, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A17">Centre for the Developing Brain, King's College, St Thomas' Campus, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for the Developing Brain, King's College, St Thomas' Campus, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author></analytic><series><title level="j">Annals of neurology</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Objectives</title><p id="P1">The concept of inflammation-induced sensitization is emerging in the field of perinatal brain injury, stroke, Alzheimer disease and multiple sclerosis. However, mechanisms underpinning this process remain unidentified.</p></sec><sec id="S2"><title>Methods</title><p id="P2">We combined <italic>in vivo</italic> systemic lipopolysaccharide (LPS) or Interleukin-1β (IL-1β) induced sensitization of neonatal and adult rodent cortical neurons to excitotoxic neurodegeneration with <italic>in vitro</italic> IL-1β sensitization of human and rodent neurons to excitotoxic neurodegeneration. Within these inflammation-induced sensitization models we assessed metabotropic glutamatergic receptor (mGluR) signaling and regulation.</p></sec><sec id="S3"><title>Results</title><p id="P3">We demonstrate for the first time that group I mGluRs mediate inflammation-induced sensitization to neuronal excitotoxicity in neonatal and adult neurons across species. Inflammation induced G protein–coupled receptor kinase 2 (GRK2) down-regulation and genetic deletion of <italic>GRK2</italic> mimicked the sensitizing effect of inflammation on excitotoxic neurodegeneration. Thus, we identify GRK2 as a potential molecular link between inflammation and mGluR-mediated sensitization.</p></sec><sec id="S4"><title>Interpretation</title><p id="P4">Collectively, our findings indicate that inflammation-induced sensitization is universal across species and ages and that group I mGluRs and GRK2 represent new avenues for neuroprotection in perinatal and adult neurological disorders.</p></sec></div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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