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Journal of Neuroscience, Vol 14, 4318-4328, Copyright © 1994 by Society for Neuroscience
Chronic electroconvulsive seizure (ECS) treatment results in expression of a long-lasting AP-1 complex in brain with altered composition and characteristics
BT Hope, MB Kelz, RS Duman and EJ Nestler
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06508.
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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