PLASTICITY-LINKED AND NEURODEGENERATION-LINKED CYCLIC-AMP RESPONSIVE ELEMENT MODULATOR INDUCIBLE CYCLIC-AMP EARLY REPRESSOR MESSENGER-RNA EXPRESSION IN THE RAT-BRAIN

Citation
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
Citations number
49
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
03064522
Volume
86
Issue
2
Year of publication
1998
Pages
499 - 510
Database
ISI
SICI code
0306-4522(1998)86:2<499:PANCRE>2.0.ZU;2-U
Abstract
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.