8027782

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7

Gene transcription is likely to play a role in the biochemical adaptations thought to underlie the long-term behavioral changes observed following various chronic treatments. The AP-1 (activator protein-1) complex is a well-studied transcription factor capable of regulating gene transcription. We therefore examined the regulation of the AP-1 complex in rat cerebral cortex and hippocampus following electroconvulsive seizures (ECS), known to induce biochemical alterations in the brain after chronic treatment. We show that 10 d of chronic ECS treatment results in an AP-1 binding complex that persists for at least 7 d in the cortex and hippocampus. In contrast, AP-1 binding returns to control levels within 18 hr of a single acute ECS. Supershift experiments and Western blots show that the chronic AP-1 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 repeated ECS. Moreover, the 37 kDa Fra band persists for at least 7 d following chronic ECS treatment, as observed for the chronic AP-1 complex. Competition experiments indicate that the relative affinities of the acute and chronic AP-1 complexes for several AP-1-like sites are similar, although there was approximately a twofold difference in the affinity for one particular AP-1-like site. The altered composition of the chronic AP-1 complex, and differences in half-life, DNA binding affinity, and possibly transcriptional activating properties are likely to cause changes in the overall pattern of gene expression, which may underlie some of the long-term biochemical adaptations observed following chronic ECS and other chronic perturbations.

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MEDLINE

0270-6474

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4318-28

pubmed-meshheading:8027782-Animals, pubmed-meshheading:8027782-Base Sequence, pubmed-meshheading:8027782-Binding, Competitive, pubmed-meshheading:8027782-Blotting, Western, pubmed-meshheading:8027782-Brain, pubmed-meshheading:8027782-DNA-Binding Proteins, pubmed-meshheading:8027782-Electroshock, pubmed-meshheading:8027782-Homeodomain Proteins, pubmed-meshheading:8027782-Male, pubmed-meshheading:8027782-Molecular Sequence Data, pubmed-meshheading:8027782-Oligonucleotide Probes, pubmed-meshheading:8027782-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:8027782-Proto-Oncogene Proteins c-fos, pubmed-meshheading:8027782-Rats, pubmed-meshheading:8027782-Rats, Sprague-Dawley, pubmed-meshheading:8027782-Replication Protein C, pubmed-meshheading:8027782-Repressor Proteins, pubmed-meshheading:8027782-Saccharomyces cerevisiae Proteins, pubmed-meshheading:8027782-Time Factors

Chronic electroconvulsive seizure (ECS) treatment results in expression of a long-lasting AP-1 complex in brain with altered composition and characteristics.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't