PLASTICITY-LINKED AND NEURODEGENERATION-LINKED CYCLIC-AMP RESPONSIVE ELEMENT MODULATOR INDUCIBLE CYCLIC-AMP EARLY REPRESSOR MESSENGER-RNA EXPRESSION IN THE RAT-BRAIN
D. Konopka et al., PLASTICITY-LINKED AND NEURODEGENERATION-LINKED CYCLIC-AMP RESPONSIVE ELEMENT MODULATOR INDUCIBLE CYCLIC-AMP EARLY REPRESSOR MESSENGER-RNA EXPRESSION IN THE RAT-BRAIN, Neuroscience, 86(2), 1998, pp. 499-510
In order to explore the role of CREM (cyclic-AMP responsive element mo
dulator) gene expression in the function of the central nervous system
, the gene transcripts were investigated in the rat brain in several c
onditions linked to increased neuronal activity. Up-regulation of CREM
messenger RNA levels in the hippocampus was found to follow intraperi
toneal administration of kainate (10 mg/kg). This increase was observe
d in both the dentate gyrus and hippocampus proper (CA subfields) and
reached its maximum at 6 h after the treatment. Intrahippocampal injec
tion of N-methyl-D-aspartate (200 nmol) resulted in elevated CREM mess
enger RNA expression as well. A similar increase of the messenger RNA
abundance was also observed in the retrosplenial cortex after treating
the female rats with a high dose (5 mg/kg) of dizocilpine maleate, an
N-methyl-D-aspartate receptor antagonist. All these conditions are li
nked to neuronal excitation and neurodegeneration. However, an increas
e in CREM messenger RNA accumulation was also observed in the visual c
ortex after exposure of dark-adapted. animals to the light, a procedur
e linked to neuronal plasticity. In the latter condition, it was found
that CREM messenger RNA reached its highest levels at 6 h, i.e. later
than the maximal increase of expression of immediate early genes such
as c-fos, jun B and zif 268, observed 45 min following the onset of v
isual stimulation. The ICER (inducible cyclic-AMP early repressor) for
m of CREM messenger RNA was identified to be induced by the light expo
sure. Finally, it was also found that cycloheximide, an inhibitor of p
rotein synthesis, overinduces CREM/ICER gene expression. Together, the
se data suggest that CREM/ICER may be responsive to neuronal activatio
n. Furthermore, given that CREM products have been shown previously to
down-regulate expression of immediate early genes in vitro, they sugg
est that ICER may function as a molecular switch involved in downregul
ation of immediate early gene expression in the rat brain. (C) 1998 IB
RO. Published by Elsevier Science Ltd.