CHRONIC ELECTROCONVULSIVE SEIZURE (ECS) TREATMENT RESULTS IN EXPRESSION OF A LONG-LASTING AP-1 COMPLEX IN BRAIN WITH ALTERED COMPOSITION AND CHARACTERISTICS

Gene transcription is likely to play a role in the biochemical adaptat ions thought to underlie the long-term behavioral changes observed fol lowing various chronic treatments. The AP-1 (activator protein-1) comp lex is a well-studied transcription factor capable of regulating gene transcription. We therefore examined the regulation of the AP-1 comple x in rat cerebral cortex and hippocampus following electroconvulsive s eizures (ECS), known to induce biochemical alterations in the brain af ter chronic treatment. We show that 10 d of chronic ECS treatment resu lts in an AP-1 binding complex that persists for at least 7 d in the c ortex and hippocampus. In contrast, AP-1 binding returns to control le vels within 18 hr of a single acute ECS. Supershift experiments and We stern blots show that the chronic AP-I complex contains two novel Fos- related antigens (Fras) of 35 and 37 kDa that do not appear following a single acute ECS. The chronically induced 35 and 37 kDa Fras and the chronic AP-1 complex show similar time courses for induction by repea ted ECS. Moreover, the 37 kDa Fra band persists for at least 7 d follo wing chronic ECS treatment, as observed for the chronic AP-1 complex. Competition experiments indicate that the relative affinities of the a cute and chronic AP-1 complexes for several AP-1-like sites are simila r, although there was approximately a twofold difference in the affini ty for one particular AP-1-like site. The altered composition of the c hronic AP-1 complex, and differences in half-life, DNA binding affinit y, and possibly transcriptional activating properties are likely to ca use changes in the overall pattern of gene expression, which may under lie some of the long-term biochemical adaptations observed following c hronic ECS and other chronic perturbations.