Article date: 2013/8/6
PubMed ID: 7905600
Journal name: Annals of neurology (ISSN: 1531-8249)
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.
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.
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.
Author List: Degos Vincent, Peineau Stéphane, Nijboer Cora, Kaindl Angela M, Sigaut Stéphanie, Favrais Géraldine, Plaisant Frank, Teissier Natacha, Gouadon Elodie, Lombet Alain, Saliba Elie, Collingridge Graham L, Maze Mervyn, Nicoletti Ferdinando, Heijnen Cobi, Mantz Jean, Kavelaars Annemieke, Gressens Pierre
Publication Types: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Article Date: 2013/03/14
Substances mentioned in the article: Cytokines; Excitatory Amino Acid Agonists; Glial Fibrillary Acidic Protein; Interleukin-1beta; Lipopolysaccharides; Receptors, Metabotropic Glutamate; metabotropic glutamate receptor type 1; Ibotenic Acid; ADRBK1 protein, human; G-Protein-Coupled Receptor Kinase 2; CAMK2A protein, human; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Phospholipase C beta; Calcium;
Mesh terms: Analysis of Variance; Animals; Animals, Newborn; Calcium/metabolism; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics; Cerebral Cortex/drug effects; Cytokines/genetics; Disease Models, Animal; Excitatory Amino Acid Agonists/toxicity; Female; G-Protein-Coupled Receptor Kinase 2/genetics; Gene Expression Regulation/drug effects; Glial Fibrillary Acidic Protein/genetics; Humans; Ibotenic Acid/toxicity; Inflammation/chemically induced; Interleukin-1beta/toxicity; Lipopolysaccharides/toxicity; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurodegenerative Diseases/etiology; Neurons/drug effects; Neurotoxicity Syndromes/etiology; Phospholipase C beta/metabolism; Pregnancy; Prenatal Exposure Delayed Effects/chemically induced; Rats; Receptors, Metabotropic Glutamate/genetics;
Citations: - 3496408