Hippocampal kindling epileptogenesis upregulates neuronal cyclooxygenase-2 expression in neocortex.
Recurrent and spontaneous seizures in epilepsy result from poorly defined cell signaling aberrations thought to include synaptic and extracellular matrix remodeling. Here we have used a rat hippocampal kindling model to study cyclooxygenase-2 (COX-2) gene expression in epileptogenesis. COX-2, encoded in an early-response gene, increases in a synaptic activity-dependent fashion and also during kainic acid-induced hippocampal damage. We found that during kindling, COX-2 induction occurred initially only in hippocampal neurons, and then spread to neocortical neurons. When rats were rekindled 34 days later, this spreading of COX-2 expression persisted. Induction of hippocampal and neocortical cytosolic phospholipase A(2) (cPLA(2)), an enzyme that catalyzes the synthesis of COX-2 substrate arachidonic acid (AA), occurred after 4 days of stimulation during kindling and rekindling. Moreover the COX-2 selective inhibitor nimesulide attenuated kindling development. We conclude that neuronal COX-2 gene induction and cPLA(2) activation are key signaling events in epileptogenesis.
Tu
Bin
B
Louisiana State University Health Sciences Center, Neuroscience Center of Excellence, New Orleans, LA 70112, USA.
Bazan
Nicolas G
NG
D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D004195:Disease Models, Animal; D004790:Enzyme Induction; D004827:Epilepsy / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007696:Kindling, Neurologic / Q000378:metabolism*; D008297:Male; D019579:Neocortex / Q000201:enzymology* / Q000473:pathology; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D010741:Phospholipases A / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D012333:RNA, Messenger; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; C012655:nimesulide