GRK2 and group I mGluR mediate inflammation-induced sensitization to excitotoxic neurodegeneration
Identifieur interne : 000798 ( Pmc/Corpus ); précédent : 000797; suivant : 000799GRK2 and group I mGluR 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.
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
Links to Exploration step
PMC:3837433Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">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><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A3">PremUP, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Anesthesia and Perioperative Care, University of California, San Francisco, USA</nlm:aff></affiliation></author><author><name sortKey="Peineau, Stephane" sort="Peineau, Stephane" uniqKey="Peineau S" first="Stéphane" last="Peineau">Stéphane Peineau</name><affiliation><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A3">PremUP, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A5">MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, Medical Sciences Building, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Nijboer, Cora" sort="Nijboer, Cora" uniqKey="Nijboer C" first="Cora" last="Nijboer">Cora Nijboer</name><affiliation><nlm:aff id="A6">Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></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><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A3">PremUP, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Sigaut, Stephanie" sort="Sigaut, Stephanie" uniqKey="Sigaut S" first="Stéphanie" last="Sigaut">Stéphanie Sigaut</name><affiliation><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A3">PremUP, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Favrais, Geraldine" sort="Favrais, Geraldine" uniqKey="Favrais G" first="Géraldine" last="Favrais">Géraldine Favrais</name><affiliation><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A3">PremUP, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Plaisant, Frank" sort="Plaisant, Frank" uniqKey="Plaisant F" first="Frank" last="Plaisant">Frank Plaisant</name><affiliation><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A3">PremUP, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Teissier, Natacha" sort="Teissier, Natacha" uniqKey="Teissier N" first="Natacha" last="Teissier">Natacha Teissier</name><affiliation><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A3">PremUP, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Gouadon, Elodie" sort="Gouadon, Elodie" uniqKey="Gouadon E" first="Elodie" last="Gouadon">Elodie Gouadon</name><affiliation><nlm:aff id="A7">Inserm, UMR 999, Labex LERMIT, Le Plessis-Robinson, France</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, France</nlm:aff></affiliation></author><author><name sortKey="Lombet, Alain" sort="Lombet, Alain" uniqKey="Lombet A" first="Alain" last="Lombet">Alain Lombet</name><affiliation><nlm:aff id="A7">Inserm, UMR 999, Labex LERMIT, Le Plessis-Robinson, France</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, France</nlm:aff></affiliation></author><author><name sortKey="Saliba, Elie" sort="Saliba, Elie" uniqKey="Saliba E" first="Elie" last="Saliba">Elie Saliba</name><affiliation><nlm:aff id="A10">Inserm, U930, Université François Rabelais de Tours, Tours, France</nlm:aff></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><nlm:aff id="A5">MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, Medical Sciences Building, Bristol, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A11">Brain Research Centre, Department of Psychiatry, University of British Columbia, Vancouver, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Department of Brain and Cognitive Sciences, Seoul National University, Seoul, Korea</nlm:aff></affiliation></author><author><name sortKey="Maze, Mervyn" sort="Maze, Mervyn" uniqKey="Maze M" first="Mervyn" last="Maze">Mervyn Maze</name><affiliation><nlm:aff id="A4">Department of Anesthesia and Perioperative Care, University of California, San Francisco, USA</nlm:aff></affiliation></author><author><name sortKey="Nicoletti, Ferdinando" sort="Nicoletti, Ferdinando" uniqKey="Nicoletti F" first="Ferdinando" last="Nicoletti">Ferdinando Nicoletti</name><affiliation><nlm:aff id="A13">Dept. of Physiology and Pharmacology, University of Rome Sapienza, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="A14">IRCCS Neuromed, Pozzilli (IS), Italy</nlm:aff></affiliation></author><author><name sortKey="Heijnen, Cobi" sort="Heijnen, Cobi" uniqKey="Heijnen C" first="Cobi" last="Heijnen">Cobi Heijnen</name><affiliation><nlm:aff id="A6">Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Mantz, Jean" sort="Mantz, Jean" uniqKey="Mantz J" first="Jean" last="Mantz">Jean Mantz</name><affiliation><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A3">PremUP, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A15">AP HP, Beaujon Hospital, Department of Anesthesia and Critical Care, Clichy, France</nlm:aff></affiliation></author><author><name sortKey="Kavelaars, Annemieke" sort="Kavelaars, Annemieke" uniqKey="Kavelaars A" first="Annemieke" last="Kavelaars">Annemieke Kavelaars</name><affiliation><nlm:aff id="A6">Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Integrative Immunology & Behavior Program, University of Illinois Urbana Champaign, IL, USA</nlm:aff></affiliation></author><author><name sortKey="Gressens, Pierre" sort="Gressens, Pierre" uniqKey="Gressens P" first="Pierre" last="Gressens">Pierre Gressens</name><affiliation><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A3">PremUP, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Centre for the Developing Brain, King's College, St Thomas' Campus, London, UK</nlm:aff></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></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><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A3">PremUP, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Anesthesia and Perioperative Care, University of California, San Francisco, USA</nlm:aff></affiliation></author><author><name sortKey="Peineau, Stephane" sort="Peineau, Stephane" uniqKey="Peineau S" first="Stéphane" last="Peineau">Stéphane Peineau</name><affiliation><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A3">PremUP, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A5">MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, Medical Sciences Building, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Nijboer, Cora" sort="Nijboer, Cora" uniqKey="Nijboer C" first="Cora" last="Nijboer">Cora Nijboer</name><affiliation><nlm:aff id="A6">Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></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><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A3">PremUP, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Sigaut, Stephanie" sort="Sigaut, Stephanie" uniqKey="Sigaut S" first="Stéphanie" last="Sigaut">Stéphanie Sigaut</name><affiliation><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A3">PremUP, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Favrais, Geraldine" sort="Favrais, Geraldine" uniqKey="Favrais G" first="Géraldine" last="Favrais">Géraldine Favrais</name><affiliation><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A3">PremUP, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Plaisant, Frank" sort="Plaisant, Frank" uniqKey="Plaisant F" first="Frank" last="Plaisant">Frank Plaisant</name><affiliation><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A3">PremUP, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Teissier, Natacha" sort="Teissier, Natacha" uniqKey="Teissier N" first="Natacha" last="Teissier">Natacha Teissier</name><affiliation><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A3">PremUP, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Gouadon, Elodie" sort="Gouadon, Elodie" uniqKey="Gouadon E" first="Elodie" last="Gouadon">Elodie Gouadon</name><affiliation><nlm:aff id="A7">Inserm, UMR 999, Labex LERMIT, Le Plessis-Robinson, France</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, France</nlm:aff></affiliation></author><author><name sortKey="Lombet, Alain" sort="Lombet, Alain" uniqKey="Lombet A" first="Alain" last="Lombet">Alain Lombet</name><affiliation><nlm:aff id="A7">Inserm, UMR 999, Labex LERMIT, Le Plessis-Robinson, France</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, France</nlm:aff></affiliation></author><author><name sortKey="Saliba, Elie" sort="Saliba, Elie" uniqKey="Saliba E" first="Elie" last="Saliba">Elie Saliba</name><affiliation><nlm:aff id="A10">Inserm, U930, Université François Rabelais de Tours, Tours, France</nlm:aff></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><nlm:aff id="A5">MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, Medical Sciences Building, Bristol, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A11">Brain Research Centre, Department of Psychiatry, University of British Columbia, Vancouver, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Department of Brain and Cognitive Sciences, Seoul National University, Seoul, Korea</nlm:aff></affiliation></author><author><name sortKey="Maze, Mervyn" sort="Maze, Mervyn" uniqKey="Maze M" first="Mervyn" last="Maze">Mervyn Maze</name><affiliation><nlm:aff id="A4">Department of Anesthesia and Perioperative Care, University of California, San Francisco, USA</nlm:aff></affiliation></author><author><name sortKey="Nicoletti, Ferdinando" sort="Nicoletti, Ferdinando" uniqKey="Nicoletti F" first="Ferdinando" last="Nicoletti">Ferdinando Nicoletti</name><affiliation><nlm:aff id="A13">Dept. of Physiology and Pharmacology, University of Rome Sapienza, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="A14">IRCCS Neuromed, Pozzilli (IS), Italy</nlm:aff></affiliation></author><author><name sortKey="Heijnen, Cobi" sort="Heijnen, Cobi" uniqKey="Heijnen C" first="Cobi" last="Heijnen">Cobi Heijnen</name><affiliation><nlm:aff id="A6">Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Mantz, Jean" sort="Mantz, Jean" uniqKey="Mantz J" first="Jean" last="Mantz">Jean Mantz</name><affiliation><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A3">PremUP, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A15">AP HP, Beaujon Hospital, Department of Anesthesia and Critical Care, Clichy, France</nlm:aff></affiliation></author><author><name sortKey="Kavelaars, Annemieke" sort="Kavelaars, Annemieke" uniqKey="Kavelaars A" first="Annemieke" last="Kavelaars">Annemieke Kavelaars</name><affiliation><nlm:aff id="A6">Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Integrative Immunology & Behavior Program, University of Illinois Urbana Champaign, IL, USA</nlm:aff></affiliation></author><author><name sortKey="Gressens, Pierre" sort="Gressens, Pierre" uniqKey="Gressens P" first="Pierre" last="Gressens">Pierre Gressens</name><affiliation><nlm:aff id="A1">Inserm, U676, Hôpital Robert Debré, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A3">PremUP, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Centre for the Developing Brain, King's College, St Thomas' Campus, London, UK</nlm:aff></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><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">7707449</journal-id><journal-id journal-id-type="pubmed-jr-id">656</journal-id><journal-id journal-id-type="nlm-ta">Ann Neurol</journal-id><journal-id journal-id-type="iso-abbrev">Ann. Neurol.</journal-id><journal-title-group><journal-title>Annals of neurology</journal-title></journal-title-group><issn pub-type="ppub">0364-5134</issn><issn pub-type="epub">1531-8249</issn></journal-meta><article-meta><article-id pub-id-type="pmid">23494575</article-id><article-id pub-id-type="pmc">3837433</article-id><article-id pub-id-type="doi">10.1002/ana.23868</article-id><article-id pub-id-type="manuscript">NIHMS516317</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>GRK2 and group I mGluR mediate inflammation-induced sensitization to excitotoxic neurodegeneration</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Degos</surname><given-names>Vincent</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Peineau</surname><given-names>Stéphane</given-names></name><xref rid="FN2" ref-type="author-notes">*</xref><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Nijboer</surname><given-names>Cora</given-names></name><xref rid="FN2" ref-type="author-notes">*</xref><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Kaindl</surname><given-names>Angela M.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref><xref rid="FN3" ref-type="author-notes">§</xref></contrib><contrib contrib-type="author"><name><surname>Sigaut</surname><given-names>Stéphanie</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Favrais</surname><given-names>Géraldine</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Plaisant</surname><given-names>Frank</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Teissier</surname><given-names>Natacha</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Gouadon</surname><given-names>Elodie</given-names></name><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Lombet</surname><given-names>Alain</given-names></name><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Saliba</surname><given-names>Elie</given-names></name><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Collingridge</surname><given-names>Graham L.</given-names></name><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A11">11</xref><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Maze</surname><given-names>Mervyn</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Nicoletti</surname><given-names>Ferdinando</given-names></name><xref ref-type="aff" rid="A13">13</xref><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Heijnen</surname><given-names>Cobi</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Mantz</surname><given-names>Jean</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>Kavelaars</surname><given-names>Annemieke</given-names></name><xref rid="FN2" ref-type="author-notes">#</xref><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A16">16</xref></contrib><contrib contrib-type="author"><name><surname>Gressens</surname><given-names>Pierre</given-names></name><xref rid="FN2" ref-type="author-notes">#</xref><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A17">17</xref></contrib></contrib-group><aff id="A1"><label>1</label>Inserm, U676, Hôpital Robert Debré, Paris, France</aff><aff id="A2"><label>2</label>Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, Paris, France</aff><aff id="A3"><label>3</label>PremUP, Paris, France</aff><aff id="A4"><label>4</label>Department of Anesthesia and Perioperative Care, University of California, San Francisco, USA</aff><aff id="A5"><label>5</label>MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, Medical Sciences Building, Bristol, UK</aff><aff id="A6"><label>6</label>Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands</aff><aff id="A7"><label>7</label>Inserm, UMR 999, Labex LERMIT, Le Plessis-Robinson, France</aff><aff id="A8"><label>8</label>Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France</aff><aff id="A9"><label>9</label>Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, France</aff><aff id="A10"><label>10</label>Inserm, U930, Université François Rabelais de Tours, Tours, France</aff><aff id="A11"><label>11</label>Brain Research Centre, Department of Psychiatry, University of British Columbia, Vancouver, Canada</aff><aff id="A12"><label>12</label>Department of Brain and Cognitive Sciences, Seoul National University, Seoul, Korea</aff><aff id="A13"><label>13</label>Dept. of Physiology and Pharmacology, University of Rome Sapienza, Italy</aff><aff id="A14"><label>14</label>IRCCS Neuromed, Pozzilli (IS), Italy</aff><aff id="A15"><label>15</label>AP HP, Beaujon Hospital, Department of Anesthesia and Critical Care, Clichy, France</aff><aff id="A16"><label>16</label>Integrative Immunology & Behavior Program, University of Illinois Urbana Champaign, IL, USA</aff><aff id="A17"><label>17</label>Centre for the Developing Brain, King's College, St Thomas' Campus, London, UK</aff><author-notes><corresp id="FN1">Corresponding author: Dr Pierre Gressens, Inserm U676, Hôpital Robert Debré, 48 blvd Serurier, F-75019 Paris, France. Phone: +33 1 40 03 19 76; Fax: +33 1 40 03 19 95; <email>pierre.gressens@inserm.fr</email></corresp><fn id="FN2" fn-type="equal"><label>*#</label><p>These authors have equally contributed to the manuscript</p></fn><fn id="FN3" fn-type="present-address"><label>§</label><p>Current addresses: Department of Pediatric Neurology and Institute of Cell and Neurobiology, Charité University Medicine Berlin, Universitätsmedizin, 10117 Berlin, Germany</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>27</day><month>9</month><year>2013</year></pub-date><pub-date pub-type="epub"><day>14</day><month>3</month><year>2013</year></pub-date><pub-date pub-type="ppub"><month>5</month><year>2013</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>5</month><year>2014</year></pub-date><volume>73</volume><issue>5</issue><elocation-id>10.1002/ana.23868</elocation-id><abstract><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></abstract><funding-group><award-group><funding-source country="United States">National Institute of Neurological Disorders and Stroke : NINDS</funding-source><award-id>R01 NS074999 || NS</award-id></award-group><award-group><funding-source country="United States">National Institute of Neurological Disorders and Stroke : NINDS</funding-source><award-id>R01 NS073939 || NS</award-id></award-group></funding-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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