Sustained induction of prostaglandin endoperoxide synthase-2 by seizures in hippocampus. Inhibition by a platelet-activating factor antagonist.
Prostaglandin G/H synthase-2 and zif-268 mRNA expression is transiently induced in rat brain by kainic acid (KA)-induced seizures and by a single electroconvulsive shock. Induction of both genes by KA shows neuroanatomical specificity in the order hippocampus > cerebral cortex > striatum > brain stem > cerebellum. Nuclear run-on and Western blotting shows that both genes are transcriptionally activated, and that kainic acid up-regulation of prostaglandin G/H synthase-2 mRNA expression in hippocampus matches increased protein levels. Whereas the magnitude of hippocampal zif-268 mRNA induction is similar in both seizure models, peak induction of prostaglandin G/H synthase-2 mRNA is 7-fold greater in the kainic acid model than in the electroconvulsive shock model and is much more prolonged. Pretreatment of animals by intracerebroventricular injection with the intracellular platelet-activating factor receptor antagonist BN 50730 strongly attenuates kainic acid and electroconvulsive shock induction of prostaglandin G/H synthase-2 expression. The drug partially inhibits electroconvulsive shock induction of zif-268, but is relatively ineffective against kainic acid-induced zif-268 expression. Seizure-induced expression of both genes involves platelet-activating factor, but the mechanisms of induction must be otherwise distinct. The selectively elevated induction of hippocampal prostaglandin G/H synthase-2 by kainic acid correlates with a neuroanatomical region in which the agonist induces neuronal damage.
Marcheselli
V L
VL
LSU Neuroscience Center, Louisiana State University Medical Center School of Medicine, New Orleans, Louisiana 70112, USA.
Bazan
N G
NG
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics; D051766:Early Growth Response Protein 1; D004558:Electric Stimulation; D004790:Enzyme Induction; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D017874:Immediate-Early Proteins; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000201:enzymology*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D010972:Platelet Activating Factor; D012333:RNA, Messenger; D014157:Transcription Factors; D011451:Prostaglandin-Endoperoxide Synthases; D007608:Kainic Acid