Sustained induction of prostaglandin endoperoxide synthase-2 by seizures in hippocampus. Inhibition by a platelet-activating factor antagonist

Abstract

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.