PT  - JOURNAL ARTICLE
AU  - BT Hope
AU  - MB Kelz
AU  - RS Duman
AU  - EJ Nestler
TI  - Chronic electroconvulsive seizure (ECS) treatment results in expression of a long-lasting AP-1 complex in brain with altered composition and characteristics
AID  - 10.1523/JNEUROSCI.14-07-04318.1994
DP  - 1994 Jul 01
TA  - The Journal of Neuroscience
PG  - 4318--4328
VI  - 14
IP  - 7
4099  - http://www.jneurosci.org/content/14/7/4318.short
4100  - http://www.jneurosci.org/content/14/7/4318.full
SO  - J. Neurosci.1994 Jul 01; 14
AB  - 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.