Repetitive electroconvulsive seizures induce activity of c-Jun N-terminal kinase and compartment-specific desensitization of c-Jun phosphorylation inthe rat brain
S. Brecht et al., Repetitive electroconvulsive seizures induce activity of c-Jun N-terminal kinase and compartment-specific desensitization of c-Jun phosphorylation inthe rat brain, MOL BRAIN R, 68(1-2), 1999, pp. 101-108
Electroconvulsive seizures (ECS) are used for therapy of pharmacoresistent
depression and are supposed to induce long-lasting neuronal alterations in
morphology and gene expression. In this study, we have investigated the pho
sphorylation of the transcription factor protein c-Jun at its serine 73 res
idue by immunohistochemistry and the activity of the c-Jun N-terminal kinas
e 1 (JNK1) by immunocomplex assay following repetitive ECS in adult rats. I
n untreated controls, nuclear c-Jun immunoreactivity, but not N-terminal ph
osphorylation, was present in a variety of neuronal populations including t
he hippocampus, the temporobasal cortex and the amygdalar complex. Daily EC
S for 1, 5 or 10 days (1 x, 5 X or 10 X ECS) did not alter the expression o
f c-Jun but caused a substantial N-terminal phosphorylation of c-Jun (phosp
ho-c-Jun). Nuclear phospho-c-Jun immunoreactivity was maximal within 15 min
following ECS, and became absent after 30 min. The highest levels of phosp
ho-c-Jun labeling were found after I X ECS in the amygdalar complex, the do
rsomedial hypothalamus and the piriform cortex. The inducibility of c-Jun N
-terminal phosphorylation was preserved in the medial amygdala and piriform
cortex, but significantly declined in the basal amygdala and medial hypoth
alamus with progressive ECS stimulation. One single ECS 3 or 5 days followi
ng 10 x ECS yielded a pattern of phospho-c-Jun as seen following 10 x ECS;
thus, a lag of 5 days was not sufficient to provoke the initial level of N-
terminal phosphorylation of c-Jun. In the dentate gyrus, c-Jun was not phos
phorylated at any investigated time inspite of its high constitutive expres
sion. In some contrast with this compartment-specific phosphorylation of c-
Jun, immunocomplex assays revealed that the JNK1 activity was strongly enha
nced in both amygdala and hippocampus. Our findings demonstrate that rapid
JNK activation and phosphorylation of c-Jun as stand-by transcription facto
r characterize the beginning of neuroplastic changes, e.g., following ECS,
a classic treatment of mental disorders. The N-terminal phosphorylation is
compartment specific and can habituate following repetitive stimulation sug
gesting that the differential activation of the JNK/c-Jun axis is part of t
he neuronal strategy to integrate transynaptic excitation. (C) 1999 Elsevie
r Science B.V, All rights reserved.