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 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.
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06508.
B T
BT
Hope
M B
MB
Kelz
R S
RS
Duman
E J
EJ
Nestler
D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D004597:Electroshock; D018398:Homeodomain Proteins; D008297:Male; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D013997:Time Factors
C096816:BCL2-related protein A1; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; D015345:Oligonucleotide Probes; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D051818:Replication Protein C