G protein–coupled receptor kinase 2 and group I metabotropic glutamate receptors mediate inflammation‐induced sensitization to excitotoxic neurodegeneration
Identifieur interne : 002B02 ( Istex/Corpus ); précédent : 002B01; suivant : 002B03G protein–coupled receptor kinase 2 and group I metabotropic glutamate receptors mediate inflammation‐induced sensitization to excitotoxic neurodegeneration
Auteurs : Vincent Degos ; Stéphane Peineau ; Cora Nijboer ; Angela M. Kaindl ; Stéphanie Sigaut ; Géraldine Favrais ; Frank Plaisant ; Natacha Teissier ; Elodie Gouadon ; Alain Lombet ; Elie Saliba ; Graham L. Collingridge ; Mervyn Maze ; Ferdinando Nicoletti ; Cobi Heijnen ; Jean Mantz ; Annemieke Kavelaars ; Pierre GressensSource :
- Annals of Neurology [ 0364-5134 ] ; 2013-05.
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.
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DOI: 10.1002/ana.23868
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">G protein–coupled receptor kinase 2 and group I metabotropic glutamate receptors 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><mods:affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>PremUP, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, San Francisco</mods:affiliation></affiliation></author><author><name sortKey="Peineau, Stephane" sort="Peineau, Stephane" uniqKey="Peineau S" first="Stéphane" last="Peineau">Stéphane Peineau</name><affiliation><mods:affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>PremUP, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>School of Physiology and Pharmacology, Medical Research Council Centre for Synaptic Plasticity, Bristol, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Nijboer, Cora" sort="Nijboer, Cora" uniqKey="Nijboer C" first="Cora" last="Nijboer">Cora Nijboer</name><affiliation><mods:affiliation>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></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><mods:affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>PremUP, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Current Address: Department of Pediatric Neurology and Institute of Cell and Neurobiology, Charité University Medicine Berlin, Universitätsmedizin, 10117 Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Sigaut, Stephanie" sort="Sigaut, Stephanie" uniqKey="Sigaut S" first="Stéphanie" last="Sigaut">Stéphanie Sigaut</name><affiliation><mods:affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>PremUP, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Favrais, Geraldine" sort="Favrais, Geraldine" uniqKey="Favrais G" first="Géraldine" last="Favrais">Géraldine Favrais</name><affiliation><mods:affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>PremUP, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Plaisant, Frank" sort="Plaisant, Frank" uniqKey="Plaisant F" first="Frank" last="Plaisant">Frank Plaisant</name><affiliation><mods:affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>PremUP, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Teissier, Natacha" sort="Teissier, Natacha" uniqKey="Teissier N" first="Natacha" last="Teissier">Natacha Teissier</name><affiliation><mods:affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>PremUP, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Gouadon, Elodie" sort="Gouadon, Elodie" uniqKey="Gouadon E" first="Elodie" last="Gouadon">Elodie Gouadon</name><affiliation><mods:affiliation>Inserm, UMR 999, Labex LERMIT, Le Plessis‐Robinson, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre Chirurgical Marie Lannelongue, Le Plessis‐Robinson, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris-Sud, Faculté de Médecine, Le Kremlin‐Bicêtre, France</mods:affiliation></affiliation></author><author><name sortKey="Lombet, Alain" sort="Lombet, Alain" uniqKey="Lombet A" first="Alain" last="Lombet">Alain Lombet</name><affiliation><mods:affiliation>Inserm, UMR 999, Labex LERMIT, Le Plessis‐Robinson, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris-Sud, Faculté de Médecine, Le Kremlin‐Bicêtre, France</mods:affiliation></affiliation></author><author><name sortKey="Saliba, Elie" sort="Saliba, Elie" uniqKey="Saliba E" first="Elie" last="Saliba">Elie Saliba</name><affiliation><mods:affiliation>Inserm, U930, Université François Rabelais de Tours, Tours, France</mods:affiliation></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><mods:affiliation>School of Physiology and Pharmacology, Medical Research Council Centre for Synaptic Plasticity, Bristol, United Kingdom</mods:affiliation></affiliation><affiliation><mods:affiliation>Brain Research Centre, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Brain and Cognitive Sciences, Seoul National University, Seoul, Korea</mods:affiliation></affiliation></author><author><name sortKey="Maze, Mervyn" sort="Maze, Mervyn" uniqKey="Maze M" first="Mervyn" last="Maze">Mervyn Maze</name><affiliation><mods:affiliation>Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, San Francisco</mods:affiliation></affiliation></author><author><name sortKey="Nicoletti, Ferdinando" sort="Nicoletti, Ferdinando" uniqKey="Nicoletti F" first="Ferdinando" last="Nicoletti">Ferdinando Nicoletti</name><affiliation><mods:affiliation>Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy</mods:affiliation></affiliation><affiliation><mods:affiliation>IRCCS Neuromed, Pozzilli (IS), Italy</mods:affiliation></affiliation></author><author><name sortKey="Heijnen, Cobi" sort="Heijnen, Cobi" uniqKey="Heijnen C" first="Cobi" last="Heijnen">Cobi Heijnen</name><affiliation><mods:affiliation>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Mantz, Jean" sort="Mantz, Jean" uniqKey="Mantz J" first="Jean" last="Mantz">Jean Mantz</name><affiliation><mods:affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>PremUP, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Anesthesia and Critical Care, Beaujon Hospital, Public Assistance Hospitals of Paris, Clichy, France</mods:affiliation></affiliation></author><author><name sortKey="Kavelaars, Annemieke" sort="Kavelaars, Annemieke" uniqKey="Kavelaars A" first="Annemieke" last="Kavelaars">Annemieke Kavelaars</name><affiliation><mods:affiliation>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation><affiliation><mods:affiliation>Integrative Immunology and Behavior Program, University of Illinois at Urbana–Champaign, IL, Urbana</mods:affiliation></affiliation></author><author><name sortKey="Gressens, Pierre" sort="Gressens, Pierre" uniqKey="Gressens P" first="Pierre" last="Gressens">Pierre Gressens</name><affiliation><mods:affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>PremUP, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre for the Developing Brain, King's College, St Thomas' Campus, London, United Kingdom</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: pierre.gressens@inserm.fr</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:E9DAFF33B4B8A61079CFCB7718AC6E84FC3203E0</idno><date when="2013" year="2013">2013</date><idno type="doi">10.1002/ana.23868</idno><idno type="url">https://api-v5.istex.fr/document/E9DAFF33B4B8A61079CFCB7718AC6E84FC3203E0/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">002B02</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">002B02</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">G protein–coupled receptor kinase 2 and group I metabotropic glutamate receptors 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><mods:affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>PremUP, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, San Francisco</mods:affiliation></affiliation></author><author><name sortKey="Peineau, Stephane" sort="Peineau, Stephane" uniqKey="Peineau S" first="Stéphane" last="Peineau">Stéphane Peineau</name><affiliation><mods:affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>PremUP, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>School of Physiology and Pharmacology, Medical Research Council Centre for Synaptic Plasticity, Bristol, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Nijboer, Cora" sort="Nijboer, Cora" uniqKey="Nijboer C" first="Cora" last="Nijboer">Cora Nijboer</name><affiliation><mods:affiliation>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></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><mods:affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>PremUP, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Current Address: Department of Pediatric Neurology and Institute of Cell and Neurobiology, Charité University Medicine Berlin, Universitätsmedizin, 10117 Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Sigaut, Stephanie" sort="Sigaut, Stephanie" uniqKey="Sigaut S" first="Stéphanie" last="Sigaut">Stéphanie Sigaut</name><affiliation><mods:affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>PremUP, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Favrais, Geraldine" sort="Favrais, Geraldine" uniqKey="Favrais G" first="Géraldine" last="Favrais">Géraldine Favrais</name><affiliation><mods:affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>PremUP, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Plaisant, Frank" sort="Plaisant, Frank" uniqKey="Plaisant F" first="Frank" last="Plaisant">Frank Plaisant</name><affiliation><mods:affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>PremUP, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Teissier, Natacha" sort="Teissier, Natacha" uniqKey="Teissier N" first="Natacha" last="Teissier">Natacha Teissier</name><affiliation><mods:affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>PremUP, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Gouadon, Elodie" sort="Gouadon, Elodie" uniqKey="Gouadon E" first="Elodie" last="Gouadon">Elodie Gouadon</name><affiliation><mods:affiliation>Inserm, UMR 999, Labex LERMIT, Le Plessis‐Robinson, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre Chirurgical Marie Lannelongue, Le Plessis‐Robinson, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris-Sud, Faculté de Médecine, Le Kremlin‐Bicêtre, France</mods:affiliation></affiliation></author><author><name sortKey="Lombet, Alain" sort="Lombet, Alain" uniqKey="Lombet A" first="Alain" last="Lombet">Alain Lombet</name><affiliation><mods:affiliation>Inserm, UMR 999, Labex LERMIT, Le Plessis‐Robinson, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris-Sud, Faculté de Médecine, Le Kremlin‐Bicêtre, France</mods:affiliation></affiliation></author><author><name sortKey="Saliba, Elie" sort="Saliba, Elie" uniqKey="Saliba E" first="Elie" last="Saliba">Elie Saliba</name><affiliation><mods:affiliation>Inserm, U930, Université François Rabelais de Tours, Tours, France</mods:affiliation></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><mods:affiliation>School of Physiology and Pharmacology, Medical Research Council Centre for Synaptic Plasticity, Bristol, United Kingdom</mods:affiliation></affiliation><affiliation><mods:affiliation>Brain Research Centre, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Brain and Cognitive Sciences, Seoul National University, Seoul, Korea</mods:affiliation></affiliation></author><author><name sortKey="Maze, Mervyn" sort="Maze, Mervyn" uniqKey="Maze M" first="Mervyn" last="Maze">Mervyn Maze</name><affiliation><mods:affiliation>Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, San Francisco</mods:affiliation></affiliation></author><author><name sortKey="Nicoletti, Ferdinando" sort="Nicoletti, Ferdinando" uniqKey="Nicoletti F" first="Ferdinando" last="Nicoletti">Ferdinando Nicoletti</name><affiliation><mods:affiliation>Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy</mods:affiliation></affiliation><affiliation><mods:affiliation>IRCCS Neuromed, Pozzilli (IS), Italy</mods:affiliation></affiliation></author><author><name sortKey="Heijnen, Cobi" sort="Heijnen, Cobi" uniqKey="Heijnen C" first="Cobi" last="Heijnen">Cobi Heijnen</name><affiliation><mods:affiliation>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Mantz, Jean" sort="Mantz, Jean" uniqKey="Mantz J" first="Jean" last="Mantz">Jean Mantz</name><affiliation><mods:affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>PremUP, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Anesthesia and Critical Care, Beaujon Hospital, Public Assistance Hospitals of Paris, Clichy, France</mods:affiliation></affiliation></author><author><name sortKey="Kavelaars, Annemieke" sort="Kavelaars, Annemieke" uniqKey="Kavelaars A" first="Annemieke" last="Kavelaars">Annemieke Kavelaars</name><affiliation><mods:affiliation>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation><affiliation><mods:affiliation>Integrative Immunology and Behavior Program, University of Illinois at Urbana–Champaign, IL, Urbana</mods:affiliation></affiliation></author><author><name sortKey="Gressens, Pierre" sort="Gressens, Pierre" uniqKey="Gressens P" first="Pierre" last="Gressens">Pierre Gressens</name><affiliation><mods:affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>PremUP, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre for the Developing Brain, King's College, St Thomas' Campus, London, United Kingdom</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: pierre.gressens@inserm.fr</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><date type="published" when="2013-05">2013-05</date><biblScope unit="volume">73</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="667">667</biblScope><biblScope unit="page" to="678">678</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">E9DAFF33B4B8A61079CFCB7718AC6E84FC3203E0</idno><idno type="DOI">10.1002/ana.23868</idno><idno type="ArticleID">ANA23868</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="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.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Vincent Degos MD, PhD</name><affiliations><json:string>Inserm, U676, Hôpital Robert Debré, Paris, France</json:string><json:string>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</json:string><json:string>PremUP, Paris, France</json:string><json:string>Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, San Francisco</json:string></affiliations></json:item><json:item><name>Stéphane Peineau PhD</name><affiliations><json:string>Inserm, U676, Hôpital Robert Debré, Paris, France</json:string><json:string>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</json:string><json:string>PremUP, Paris, France</json:string><json:string>School of Physiology and Pharmacology, Medical Research Council Centre for Synaptic Plasticity, Bristol, United Kingdom</json:string></affiliations></json:item><json:item><name>Cora Nijboer PhD</name><affiliations><json:string>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands</json:string></affiliations></json:item><json:item><name>Angela M. Kaindl MD, PhD</name><affiliations><json:string>Inserm, U676, Hôpital Robert Debré, Paris, France</json:string><json:string>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</json:string><json:string>PremUP, Paris, France</json:string><json:string>Current Address: Department of Pediatric Neurology and Institute of Cell and Neurobiology, Charité University Medicine Berlin, Universitätsmedizin, 10117 Berlin, Germany</json:string></affiliations></json:item><json:item><name>Stéphanie Sigaut MD</name><affiliations><json:string>Inserm, U676, Hôpital Robert Debré, Paris, France</json:string><json:string>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</json:string><json:string>PremUP, Paris, France</json:string></affiliations></json:item><json:item><name>Géraldine Favrais MD, PhD</name><affiliations><json:string>Inserm, U676, Hôpital Robert Debré, Paris, France</json:string><json:string>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</json:string><json:string>PremUP, Paris, France</json:string></affiliations></json:item><json:item><name>Frank Plaisant MD, PhD</name><affiliations><json:string>Inserm, U676, Hôpital Robert Debré, Paris, France</json:string><json:string>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</json:string><json:string>PremUP, Paris, France</json:string></affiliations></json:item><json:item><name>Natacha Teissier MD, PhD</name><affiliations><json:string>Inserm, U676, Hôpital Robert Debré, Paris, France</json:string><json:string>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</json:string><json:string>PremUP, Paris, France</json:string></affiliations></json:item><json:item><name>Elodie Gouadon PhD</name><affiliations><json:string>Inserm, UMR 999, Labex LERMIT, Le Plessis‐Robinson, France</json:string><json:string>Centre Chirurgical Marie Lannelongue, Le Plessis‐Robinson, France</json:string><json:string>Université Paris-Sud, Faculté de Médecine, Le Kremlin‐Bicêtre, France</json:string></affiliations></json:item><json:item><name>Alain Lombet PhD</name><affiliations><json:string>Inserm, UMR 999, Labex LERMIT, Le Plessis‐Robinson, France</json:string><json:string>Université Paris-Sud, Faculté de Médecine, Le Kremlin‐Bicêtre, France</json:string></affiliations></json:item><json:item><name>Elie Saliba MD, PhD</name><affiliations><json:string>Inserm, U930, Université François Rabelais de Tours, Tours, France</json:string></affiliations></json:item><json:item><name>Graham L. Collingridge PhD</name><affiliations><json:string>School of Physiology and Pharmacology, Medical Research Council Centre for Synaptic Plasticity, Bristol, United Kingdom</json:string><json:string>Brain Research Centre, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada</json:string><json:string>Department of Brain and Cognitive Sciences, Seoul National University, Seoul, Korea</json:string></affiliations></json:item><json:item><name>Mervyn Maze MB, ChB</name><affiliations><json:string>Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, San Francisco</json:string></affiliations></json:item><json:item><name>Ferdinando Nicoletti</name><affiliations><json:string>Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy</json:string><json:string>IRCCS Neuromed, Pozzilli (IS), Italy</json:string></affiliations></json:item><json:item><name>Cobi Heijnen PhD</name><affiliations><json:string>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands</json:string></affiliations></json:item><json:item><name>Jean Mantz MD, PhD</name><affiliations><json:string>Inserm, U676, Hôpital Robert Debré, Paris, France</json:string><json:string>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</json:string><json:string>PremUP, Paris, France</json:string><json:string>Department of Anesthesia and Critical Care, Beaujon Hospital, Public Assistance Hospitals of Paris, Clichy, France</json:string></affiliations></json:item><json:item><name>Annemieke Kavelaars PhD</name><affiliations><json:string>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands</json:string><json:string>Integrative Immunology and Behavior Program, University of Illinois at Urbana–Champaign, IL, Urbana</json:string></affiliations></json:item><json:item><name>Pierre Gressens MD, PhD</name><affiliations><json:string>Inserm, U676, Hôpital Robert Debré, Paris, France</json:string><json:string>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</json:string><json:string>PremUP, Paris, France</json:string><json:string>Centre for the Developing Brain, King's College, St Thomas' Campus, London, United Kingdom</json:string><json:string>E-mail: pierre.gressens@inserm.fr</json:string></affiliations></json:item></author><articleId><json:string>ANA23868</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><qualityIndicators><score>6.324</score><pdfVersion>1.5</pdfVersion><pdfPageSize>612 x 800.957 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uri="https://api-v5.istex.fr/document/E9DAFF33B4B8A61079CFCB7718AC6E84FC3203E0/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">G protein–coupled receptor kinase 2 and group I metabotropic glutamate receptors mediate inflammation‐induced sensitization to excitotoxic neurodegeneration</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Blackwell Publishing Ltd</publisher><availability><p>Copyright © 2013 American Neurological AssociationCopyright © 2013 American Neurological Association</p></availability><date>2013-02-18</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">G protein–coupled receptor kinase 2 and group I metabotropic glutamate receptors mediate inflammation‐induced sensitization to excitotoxic neurodegeneration</title><author xml:id="author-1"><persName><forename type="first">Vincent</forename><surname>Degos</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</affiliation><affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</affiliation><affiliation>PremUP, Paris, France</affiliation><affiliation>Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, San Francisco</affiliation></author><author xml:id="author-2"><persName><forename type="first">Stéphane</forename><surname>Peineau</surname></persName><roleName type="degree">PhD</roleName><affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</affiliation><affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</affiliation><affiliation>PremUP, Paris, France</affiliation><affiliation>School of Physiology and Pharmacology, Medical Research Council Centre for Synaptic Plasticity, Bristol, United Kingdom</affiliation></author><author xml:id="author-3"><persName><forename type="first">Cora</forename><surname>Nijboer</surname></persName><roleName type="degree">PhD</roleName><affiliation>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation></author><author xml:id="author-4"><persName><forename type="first">Angela M.</forename><surname>Kaindl</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</affiliation><affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</affiliation><affiliation>PremUP, Paris, France</affiliation><affiliation>Current Address: Department of Pediatric Neurology and Institute of Cell and Neurobiology, Charité University Medicine Berlin, Universitätsmedizin, 10117 Berlin, Germany</affiliation></author><author xml:id="author-5"><persName><forename type="first">Stéphanie</forename><surname>Sigaut</surname></persName><roleName type="degree">MD</roleName><affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</affiliation><affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</affiliation><affiliation>PremUP, Paris, France</affiliation></author><author xml:id="author-6"><persName><forename type="first">Géraldine</forename><surname>Favrais</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</affiliation><affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</affiliation><affiliation>PremUP, Paris, France</affiliation></author><author xml:id="author-7"><persName><forename type="first">Frank</forename><surname>Plaisant</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</affiliation><affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</affiliation><affiliation>PremUP, Paris, France</affiliation></author><author xml:id="author-8"><persName><forename type="first">Natacha</forename><surname>Teissier</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</affiliation><affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</affiliation><affiliation>PremUP, Paris, France</affiliation></author><author xml:id="author-9"><persName><forename type="first">Elodie</forename><surname>Gouadon</surname></persName><roleName type="degree">PhD</roleName><affiliation>Inserm, UMR 999, Labex LERMIT, Le Plessis‐Robinson, France</affiliation><affiliation>Centre Chirurgical Marie Lannelongue, Le Plessis‐Robinson, France</affiliation><affiliation>Université Paris-Sud, Faculté de Médecine, Le Kremlin‐Bicêtre, France</affiliation></author><author xml:id="author-10"><persName><forename type="first">Alain</forename><surname>Lombet</surname></persName><roleName type="degree">PhD</roleName><affiliation>Inserm, UMR 999, Labex LERMIT, Le Plessis‐Robinson, France</affiliation><affiliation>Université Paris-Sud, Faculté de Médecine, Le Kremlin‐Bicêtre, France</affiliation></author><author xml:id="author-11"><persName><forename type="first">Elie</forename><surname>Saliba</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Inserm, U930, Université François Rabelais de Tours, Tours, France</affiliation></author><author xml:id="author-12"><persName><forename type="first">Graham L.</forename><surname>Collingridge</surname></persName><roleName type="degree">PhD</roleName><affiliation>School of Physiology and Pharmacology, Medical Research Council Centre for Synaptic Plasticity, Bristol, United Kingdom</affiliation><affiliation>Brain Research Centre, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada</affiliation><affiliation>Department of Brain and Cognitive Sciences, Seoul National University, Seoul, Korea</affiliation></author><author xml:id="author-13"><persName><forename type="first">Mervyn</forename><surname>Maze</surname></persName><roleName type="degree">MB, ChB</roleName><affiliation>Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, San Francisco</affiliation></author><author xml:id="author-14"><persName><forename type="first">Ferdinando</forename><surname>Nicoletti</surname></persName><affiliation>Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy</affiliation><affiliation>IRCCS Neuromed, Pozzilli (IS), Italy</affiliation></author><author xml:id="author-15"><persName><forename type="first">Cobi</forename><surname>Heijnen</surname></persName><roleName type="degree">PhD</roleName><affiliation>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation></author><author xml:id="author-16"><persName><forename type="first">Jean</forename><surname>Mantz</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</affiliation><affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</affiliation><affiliation>PremUP, Paris, France</affiliation><affiliation>Department of Anesthesia and Critical Care, Beaujon Hospital, Public Assistance Hospitals of Paris, Clichy, France</affiliation></author><author xml:id="author-17"><persName><forename type="first">Annemieke</forename><surname>Kavelaars</surname></persName><roleName type="degree">PhD</roleName><affiliation>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation><affiliation>Integrative Immunology and Behavior Program, University of Illinois at Urbana–Champaign, IL, Urbana</affiliation></author><author xml:id="author-18"><persName><forename type="first">Pierre</forename><surname>Gressens</surname></persName><roleName type="degree">MD, PhD</roleName><email>pierre.gressens@inserm.fr</email><affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</affiliation><affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</affiliation><affiliation>PremUP, Paris, France</affiliation><affiliation>Centre for the Developing Brain, King's College, St Thomas' Campus, London, United Kingdom</affiliation></author></analytic><monogr><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="pISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><idno type="DOI">10.1002/(ISSN)1531-8249</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><date type="published" when="2013-05"></date><biblScope unit="volume">73</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="667">667</biblScope><biblScope unit="page" to="678">678</biblScope></imprint></monogr><idno type="istex">E9DAFF33B4B8A61079CFCB7718AC6E84FC3203E0</idno><idno type="DOI">10.1002/ana.23868</idno><idno type="ArticleID">ANA23868</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2013-02-18</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>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></abstract><abstract><p>We combined in vivo systemic lipopolysaccharide‐induced or interleukin (IL)−1β–induced sensitization of neonatal and adult rodent cortical neurons to excitotoxic neurodegeneration with in vitro IL‐1β sensitization of human and rodent neurons to excitotoxic neurodegeneration. Within these inflammation‐induced sensitization models, we assessed metabotropic glutamate receptors (mGluR) signaling and regulation.</p></abstract><abstract><p>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) downregulation and genetic deletion of GRK2 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></abstract><abstract><p>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. 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E‐mail: <email>pierre.gressens@inserm.fr</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:ANA.ANA23868.pdf"></link></linkGroup></publicationMeta><contentMeta><titleGroup><title type="main">G protein–coupled receptor kinase 2 and group I metabotropic glutamate receptors mediate inflammation‐induced sensitization to excitotoxic neurodegeneration</title><title type="short">Excitotoxic Neurodegeneration</title><title type="shortAuthors">Degos et al</title></titleGroup><creators><creator affiliationRef="#ana23868-aff-0001 #ana23868-aff-0002 #ana23868-aff-0003 #ana23868-aff-0004" creatorRole="author" xml:id="ana23868-cr-0001"><personName><givenNames>Vincent</givenNames><familyName>Degos</familyName><degrees>MD, PhD</degrees></personName></creator><creator affiliationRef="#ana23868-aff-0001 #ana23868-aff-0002 #ana23868-aff-0003 #ana23868-aff-0005" creatorRole="author" 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xml:id="ana23868-cr-0014"><personName><givenNames>Ferdinando</givenNames><familyName>Nicoletti</familyName></personName></creator><creator affiliationRef="#ana23868-aff-0006" creatorRole="author" xml:id="ana23868-cr-0015"><personName><givenNames>Cobi</givenNames><familyName>Heijnen</familyName><degrees>PhD</degrees></personName></creator><creator affiliationRef="#ana23868-aff-0001 #ana23868-aff-0002 #ana23868-aff-0003 #ana23868-aff-0015" creatorRole="author" xml:id="ana23868-cr-0016"><personName><givenNames>Jean</givenNames><familyName>Mantz</familyName><degrees>MD, PhD</degrees></personName></creator><creator affiliationRef="#ana23868-aff-0006 #ana23868-aff-0016" creatorRole="author" xml:id="ana23868-cr-0017"><personName><givenNames>Annemieke</givenNames><familyName>Kavelaars</familyName><degrees>PhD</degrees></personName></creator><creator affiliationRef="#ana23868-aff-0001 #ana23868-aff-0002 #ana23868-aff-0003 #ana23868-aff-0017" corresponding="yes" creatorRole="author" xml:id="ana23868-cr-0018"><personName><givenNames>Pierre</givenNames><familyName>Gressens</familyName><degrees>MD, PhD</degrees></personName></creator></creators><affiliationGroup><affiliation countryCode="FR" type="organization" xml:id="ana23868-aff-0001"><orgDiv>Inserm, U676</orgDiv><orgName>Hôpital Robert Debré</orgName><address><city>Paris</city><country>France</country></address></affiliation><affiliation countryCode="FR" type="organization" xml:id="ana23868-aff-0002"><orgName>Université Paris Diderot</orgName><address><street>Sorbonne Paris Cité, UMRS 676</street><city>Paris</city><countryPart>France</countryPart></address></affiliation><affiliation countryCode="FR" type="organization" xml:id="ana23868-aff-0003"><orgName>PremUP</orgName><address><city>Paris</city><country>France</country></address></affiliation><affiliation countryCode="US" type="organization" xml:id="ana23868-aff-0004"><orgDiv>Department of Anesthesia and Perioperative Care</orgDiv><orgName>University of California, San Francisco</orgName><address><city>San Francisco</city><countryPart>CA</countryPart></address></affiliation><affiliation countryCode="GB" type="organization" xml:id="ana23868-aff-0005"><orgDiv>School of Physiology and Pharmacology</orgDiv><orgName>Medical Research Council Centre for Synaptic Plasticity</orgName><address><city>Bristol</city><country>United Kingdom</country></address></affiliation><affiliation countryCode="NL" type="organization" xml:id="ana23868-aff-0006"><orgDiv>Laboratory for Neuroimmunology and Developmental Origins of Disease</orgDiv><orgName>University Medical Center Utrecht</orgName><address><city>Utrecht</city><country>the Netherlands</country></address></affiliation><affiliation countryCode="FR" type="organization" xml:id="ana23868-aff-0007"><orgDiv>Inserm, UMR 999</orgDiv><orgName>Labex LERMIT</orgName><address><street>Le Plessis‐Robinson</street><country>France</country></address></affiliation><affiliation countryCode="FR" type="organization" xml:id="ana23868-aff-0008"><orgName>Centre Chirurgical Marie Lannelongue</orgName><address><street>Le Plessis‐Robinson</street><country>France</country></address></affiliation><affiliation countryCode="FR" type="organization" xml:id="ana23868-aff-0009"><orgDiv>Université Paris-Sud</orgDiv><orgName>Faculté de Médecine</orgName><address><street>Le Kremlin‐Bicêtre</street><country>France</country></address></affiliation><affiliation countryCode="FR" type="organization" xml:id="ana23868-aff-0010"><orgName>Inserm, U930, Université François Rabelais de Tours</orgName><address><city>Tours</city><country>France</country></address></affiliation><affiliation countryCode="CA" type="organization" xml:id="ana23868-aff-0011"><orgDiv>Brain Research Centre, Department of Psychiatry</orgDiv><orgName>University of British Columbia</orgName><address><city>Vancouver</city><countryPart>British Columbia</countryPart><country>Canada</country></address></affiliation><affiliation type="organization" xml:id="ana23868-aff-0012"><orgDiv>Department of Brain and Cognitive Sciences</orgDiv><orgName>Seoul National University</orgName><address><city>Seoul</city><country>Korea</country></address></affiliation><affiliation countryCode="IT" type="organization" xml:id="ana23868-aff-0013"><orgDiv>Department of Physiology and Pharmacology</orgDiv><orgName>Sapienza University of Rome</orgName><address><city>Rome</city><country>Italy</country></address></affiliation><affiliation countryCode="IT" type="organization" xml:id="ana23868-aff-0014"><orgName>IRCCS Neuromed</orgName><address><city>Pozzilli (IS)</city><country>Italy</country></address></affiliation><affiliation countryCode="FR" type="organization" xml:id="ana23868-aff-0015"><orgDiv>Department of Anesthesia and Critical Care</orgDiv><orgName>Beaujon Hospital</orgName><address><street>Public Assistance Hospitals of Paris</street><city>Clichy</city><country>France</country></address></affiliation><affiliation countryCode="US" type="organization" xml:id="ana23868-aff-0016"><orgDiv>Integrative Immunology and Behavior Program</orgDiv><orgName>University of Illinois at Urbana–Champaign</orgName><address><city>Urbana</city><countryPart>IL</countryPart></address></affiliation><affiliation countryCode="GB" type="organization" xml:id="ana23868-aff-0017"><orgDiv>Centre for the Developing Brain, King's College</orgDiv><orgName>St Thomas' Campus</orgName><address><city>London</city><country>United Kingdom</country></address></affiliation><affiliation countryCode="GB" type="organization" xml:id="ana23868-aff-0018"><orgDiv>Department of Pediatric Neurology and Institute of Cell and Neurobiology</orgDiv><orgDiv>Charité University Medicine Berlin</orgDiv><orgName>Universitätsmedizin</orgName><address><countryPart>10117 Berlin</countryPart><country>Germany</country></address></affiliation></affiliationGroup><supportingInformation><p>Additional supporting information can be found in the online version of this article.</p><supportingInfoItem><mediaResource alt="application/docx" href="urn-x:wiley:03645134:media:ana23868:ana23868-sup-0001-suppinfo"></mediaResource><caption><p>Supplementary Figure 1. Time‐lines of the <i>in vivo</i> and <i>in vitro</i> rodent experiments.</p><p>Supplementary Figure 2. Absence of sensitizing effect following activation of AMPA/kainate receptors.</p><p>Supplementary Figure 3. Percentage of non‐responsive neurons to calcium mobilization after ibotenate exposure in IL‐1β and PBS groups.</p><p>Supplementary Figure 4. GRK2 immunostaining in IL‐1β and PBS‐treated mouse primary neurons.</p><p>Supplementary Figure 5. Effect of astrocyte deletion of GRK2.</p><p>Supplementary Table 1. Sample size and number of replicates for each experiment</p><p>Supplementary Table 2. Sequences of oligonucleotide primers used for qRT‐PCR</p></caption></supportingInfoItem></supportingInformation><abstractGroup><abstract type="main"><section xml:id="ana23868-sec-0001"><title type="main">Objective</title><p>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></section><section xml:id="ana23868-sec-0002"><title type="main">Methods</title><p>We combined in vivo systemic lipopolysaccharide‐induced or interleukin (IL)−1β–induced sensitization of neonatal and adult rodent cortical neurons to excitotoxic neurodegeneration with in vitro IL‐1β sensitization of human and rodent neurons to excitotoxic neurodegeneration. Within these inflammation‐induced sensitization models, we assessed metabotropic glutamate receptors (mGluR) signaling and regulation.</p></section><section xml:id="ana23868-sec-0003"><title type="main">Results</title><p>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) downregulation and genetic deletion of <i>GRK2</i> 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></section><section xml:id="ana23868-sec-0004"><title type="main">Interpretation</title><p>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. Ann Neurol 2013;73:667–678</p></section></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>G protein–coupled receptor kinase 2 and group I metabotropic glutamate receptors mediate inflammation‐induced sensitization to excitotoxic neurodegeneration</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Excitotoxic Neurodegeneration</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>G protein–coupled receptor kinase 2 and group I metabotropic glutamate receptors mediate inflammation‐induced sensitization to excitotoxic neurodegeneration</title></titleInfo><name type="personal"><namePart type="given">Vincent</namePart><namePart type="family">Degos</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</affiliation><affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</affiliation><affiliation>PremUP, Paris, France</affiliation><affiliation>Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, San Francisco</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stéphane</namePart><namePart type="family">Peineau</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</affiliation><affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</affiliation><affiliation>PremUP, Paris, France</affiliation><affiliation>School of Physiology and Pharmacology, Medical Research Council Centre for Synaptic Plasticity, Bristol, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Cora</namePart><namePart type="family">Nijboer</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Angela M.</namePart><namePart type="family">Kaindl</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</affiliation><affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</affiliation><affiliation>PremUP, Paris, France</affiliation><affiliation>Current Address: Department of Pediatric Neurology and Institute of Cell and Neurobiology, Charité University Medicine Berlin, Universitätsmedizin, 10117 Berlin, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stéphanie</namePart><namePart type="family">Sigaut</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</affiliation><affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</affiliation><affiliation>PremUP, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Géraldine</namePart><namePart type="family">Favrais</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</affiliation><affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</affiliation><affiliation>PremUP, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Frank</namePart><namePart type="family">Plaisant</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</affiliation><affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</affiliation><affiliation>PremUP, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Natacha</namePart><namePart type="family">Teissier</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</affiliation><affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</affiliation><affiliation>PremUP, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Elodie</namePart><namePart type="family">Gouadon</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Inserm, UMR 999, Labex LERMIT, Le Plessis‐Robinson, France</affiliation><affiliation>Centre Chirurgical Marie Lannelongue, Le Plessis‐Robinson, France</affiliation><affiliation>Université Paris-Sud, Faculté de Médecine, Le Kremlin‐Bicêtre, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alain</namePart><namePart type="family">Lombet</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Inserm, UMR 999, Labex LERMIT, Le Plessis‐Robinson, France</affiliation><affiliation>Université Paris-Sud, Faculté de Médecine, Le Kremlin‐Bicêtre, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Elie</namePart><namePart type="family">Saliba</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Inserm, U930, Université François Rabelais de Tours, Tours, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Graham L.</namePart><namePart type="family">Collingridge</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>School of Physiology and Pharmacology, Medical Research Council Centre for Synaptic Plasticity, Bristol, United Kingdom</affiliation><affiliation>Brain Research Centre, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada</affiliation><affiliation>Department of Brain and Cognitive Sciences, Seoul National University, Seoul, Korea</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mervyn</namePart><namePart type="family">Maze</namePart><namePart type="termsOfAddress">MB, ChB</namePart><affiliation>Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, San Francisco</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ferdinando</namePart><namePart type="family">Nicoletti</namePart><affiliation>Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy</affiliation><affiliation>IRCCS Neuromed, Pozzilli (IS), Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Cobi</namePart><namePart type="family">Heijnen</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean</namePart><namePart type="family">Mantz</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</affiliation><affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</affiliation><affiliation>PremUP, Paris, France</affiliation><affiliation>Department of Anesthesia and Critical Care, Beaujon Hospital, Public Assistance Hospitals of Paris, Clichy, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Annemieke</namePart><namePart type="family">Kavelaars</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation><affiliation>Integrative Immunology and Behavior Program, University of Illinois at Urbana–Champaign, IL, Urbana</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Pierre</namePart><namePart type="family">Gressens</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Inserm, U676, Hôpital Robert Debré, Paris, France</affiliation><affiliation>Université Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</affiliation><affiliation>PremUP, Paris, France</affiliation><affiliation>Centre for the Developing Brain, King's College, St Thomas' Campus, London, United Kingdom</affiliation><affiliation>E-mail: pierre.gressens@inserm.fr</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><dateIssued encoding="w3cdtf">2013-05</dateIssued><dateCreated encoding="w3cdtf">2013-02-18</dateCreated><dateCaptured encoding="w3cdtf">2012-07-13</dateCaptured><dateValid encoding="w3cdtf">2013-02-05</dateValid><copyrightDate encoding="w3cdtf">2013</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><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.</abstract><abstract>We combined in vivo systemic lipopolysaccharide‐induced or interleukin (IL)−1β–induced sensitization of neonatal and adult rodent cortical neurons to excitotoxic neurodegeneration with in vitro IL‐1β sensitization of human and rodent neurons to excitotoxic neurodegeneration. Within these inflammation‐induced sensitization models, we assessed metabotropic glutamate receptors (mGluR) signaling and regulation.</abstract><abstract>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) downregulation and genetic deletion of GRK2 mimicked the sensitizing effect of inflammation on excitotoxic neurodegeneration. Thus, we identify GRK2 as a potential molecular link between inflammation and mGluR‐mediated sensitization.</abstract><abstract>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. Ann Neurol 2013;73:667–678</abstract><relatedItem type="host"><titleInfo><title>Annals of Neurology</title></titleInfo><titleInfo type="abbreviated"><title>Ann Neurol.</title></titleInfo><genre type="journal">journal</genre><note type="content"> Additional supporting information can be found in the online version of this article.Supporting Info Item: Supplementary Figure 1. Time‐lines of the in vivo and in vitro rodent experiments. Supplementary Figure 2. Absence of sensitizing effect following activation of AMPA/kainate receptors. Supplementary Figure 3. Percentage of non‐responsive neurons to calcium mobilization after ibotenate exposure in IL‐1β and PBS groups. Supplementary Figure 4. GRK2 immunostaining in IL‐1β and PBS‐treated mouse primary neurons. Supplementary Figure 5. Effect of astrocyte deletion of GRK2. Supplementary Table 1. Sample size and number of replicates for each experiment Supplementary Table 2. Sequences of oligonucleotide primers used for qRT‐PCR - </note><subject><genre>article-category</genre><topic>Original Article</topic></subject><identifier type="ISSN">0364-5134</identifier><identifier type="eISSN">1531-8249</identifier><identifier type="DOI">10.1002/(ISSN)1531-8249</identifier><identifier type="PublisherID">ANA</identifier><part><date>2013</date><detail type="volume"><caption>vol.</caption><number>73</number></detail><detail type="issue"><caption>no.</caption><number>5</number></detail><extent unit="pages"><start>667</start><end>678</end><total>12</total></extent></part></relatedItem><identifier type="istex">E9DAFF33B4B8A61079CFCB7718AC6E84FC3203E0</identifier><identifier type="DOI">10.1002/ana.23868</identifier><identifier type="ArticleID">ANA23868</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2013 American Neurological AssociationCopyright © 2013 American Neurological Association</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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