title: NMDA preconditioning protects against quinolinic acid-induced seizures via PKA, PI3K and MAPK/ERK signaling pathways.
abstract: Preconditioning by N-methyl-d-aspartate (NMDA) may be promoted in vivo by the administration of a sub-convulsing dose of NMDA, with a neuroprotective effect against seizures and neuronal death induced by the infusion of quinolinic acid (QA) in mice. This study aimed to evaluate the participation of protein kinase C (PKC), cyclic AMP-dependent protein kinase (PKA), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK), Ca(2+)/calmodulin dependent protein kinase II (CaMKII) and phosphatidilinositol-3 kinase (PI3K) signaling pathways in this neuroprotection model. Adult Swiss male mice were preconditioned with NMDA 24 h before the infusion of QA, and were treated with inhibitors of the aforementioned signaling pathways either 15 min before the preconditioning or infusion of QA. Inhibition of the PKA and PI3K pathways abolished the protection evoked by NMDA, and inhibition of the MEK pathway significantly diminished this protection. Treatment with PKC and CaMKII inhibitors did not alter the protection rate. Inhibition of the MEK and PKC pathways resulted in an increased mortality rate when followed by the infusion of QA, or NMDA preconditioning and QA infusion, respectively. These results suggest that the PKA, PI3K and MEK pathways have a crucial role in the achievement of a neuroprotective state following preconditioning.
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900, Florianópolis, SC, Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: de Araújo Herculano
authors.forename: Samuel
authors.initials: S
authors.lastname: Vandresen-Filho
authors.forename: Wagner Carbolin
authors.initials: WC
authors.lastname: Martins
authors.forename: Carina Rodrigues
authors.initials: CR
authors.lastname: Boeck
authors.forename: Carla Inês
authors.initials: CI
authors.lastname: Tasca
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D007276:Injections, Intraventricular; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017378:Quinolinic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology; D000077191:Wortmannin
chemical_list: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000730:Androstadienes; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017868:Cyclic AMP-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids; D007546:Isoquinolines; D020928:Mitogen-Activated Protein Kinases; D016202:N-Methylaspartate; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D017378:Quinolinic Acid; D016194:Receptors, N-Methyl-D-Aspartate; D013449:Sulfonamides; D000077191:Wortmannin; C063302:KN 62; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one