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

J Neurosci. 1994 Jul;14(7):4318-28. doi: 10.1523/JNEUROSCI.14-07-04318.1994.

Abstract

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.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Binding, Competitive
  • Blotting, Western
  • Brain / metabolism*
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism*
  • Electroshock*
  • Homeodomain Proteins*
  • Male
  • Minor Histocompatibility Antigens
  • Molecular Sequence Data
  • Oligonucleotide Probes / genetics
  • Proto-Oncogene Proteins c-bcl-2*
  • Proto-Oncogene Proteins c-fos / analysis
  • Proto-Oncogene Proteins c-fos / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Replication Protein C
  • Repressor Proteins*
  • Saccharomyces cerevisiae Proteins*
  • Time Factors

Substances

  • BCL2-related protein A1
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • MATA1 protein, S cerevisiae
  • Minor Histocompatibility Antigens
  • Oligonucleotide Probes
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-fos
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Replication Protein C