Plasticity- and neurodegeneration-linked cyclic-AMP responsive element modulator/inducible cyclic-AMP early repressor messenger RNA expression in the rat brain
| Autor: | A. Szklarczyk, Robert K. Filipkowski, Leszek Kaczmarek, D Konopka, D Nowicka, A Trauzold, Michal Hetman |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Male
endocrine system medicine.medical_specialty N-Methylaspartate Light Transcription Genetic Repressor Hippocampus c-Fos Functional Laterality Immediate-Early Proteins Cyclic AMP Response Element Modulator Genes jun Internal medicine Gene expression Cyclic AMP medicine Protein biosynthesis Animals RNA Messenger Rats Wistar Transcription factor In Situ Hybridization Early Growth Response Protein 1 Messenger RNA Kainic Acid Neuronal Plasticity biology General Neuroscience Brain Genes fos Darkness Rats DNA-Binding Proteins Repressor Proteins Endocrinology Gene Expression Regulation Regulatory sequence biology.protein Female Dizocilpine Maleate Immediate early gene Photic Stimulation Transcription Factors |
| Zdroj: | Neuroscience. 86:499-510 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/s0306-4522(98)00046-3 |
| Popis: | In order to explore the role of CREM (cyclic-AMP responsive element modulator) gene expression in the function of the central nervous system, the gene transcripts were investigated in the rat brain in several conditions linked to increased neuronal activity. Up-regulation of CREM messenger RNA levels in the hippocampus was found to follow intraperitoneal administration of kainate (10 mg/kg). This increase was observed in both the dentate gyrus and hippocampus proper (CA subfields) and reached its maximum at 6 h after the treatment. Intrahippocampal injection of N -methyl- d -aspartate (200 nmol) resulted in elevated CREM messenger 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 linked to neuronal excitation and neurodegeneration. However, an increase in CREM messenger RNA accumulation was also observed in the visual cortex after exposure of dark-adapted animals to the light, a procedure 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 visual stimulation. The ICER (inducible cyclic-AMP early repressor) form of CREM messenger RNA was identified to be induced by the light exposure. Finally, it was also found that cycloheximide, an inhibitor of protein synthesis, overinduces CREM/ICER gene expression. Together, these data suggest that CREM/ICER may be responsive to neuronal activation. Furthermore, given that CREM products have been shown previously to down-regulate expression of immediate early genes in vitro , they suggest that ICER may function as a molecular switch involved in down-regulation of immediate early gene expression in the rat brain. |
| Databáze: | OpenAIRE |
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