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Identification of corticosteroid-responsive genes in rat hippocampus using serial analysis of gene expression
N A Datson1, J van der Perk, E R de Kloet
1Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University Medical Centre, 2300 RA Leiden, The Netherlands. datson_n@lacdr.leidenuniv.nl
Abstract:
Adrenal corticosteroids (CORT) have a profound effect on the function of the hippocampus. This is mediated in a coordinated manner by mineralocorticoid (MR) and glucocorticoid receptors (GR) via activation or repression of target genes. The aim of this study was to identify, using serial analysis of gene expression (SAGE), CORT-responsive hippocampal genes regulated via MR and/or GR. SAGE profiles were compared under different conditions of CORT exposure, resulting in the identification of 203 CORT-responsive genes that are involved in many different cellular processes like, energy expenditure and cellular metabolism; protein synthesis and turnover; signal transduction and neuronal connectivity and neurotransmission. Besides some previously identified CORT-responsive genes, the majority of the genes identified in this study were novel. In situ hybridization revealed that six randomly chosen CORT-responsive genes had distinct expression patterns in neurons of the hippocampus. In addition, using in situ hybridization, we confirmed that these six genes were indeed regulated by CORT, underscoring the validity of the SAGE data. Comparison of MR- and GR-dependent expression profiles revealed that the majority of the CORT-responsive genes were regulated either by activated MR or by activated GR, while only a few genes were responsive to both activated MR and GR. This indicates that the molecular basis for the differential effects of activated MR and GR is activation or repression of distinct, yet partially overlapping sets of genes. The putative CORT-responsive genes identified here will provide insight into the molecular mechanisms underlying the differential and sometimes opposing effects of MR and GR on neuronal excitability, memory formation and behaviour as well as their role in neuronal protection and damage.
Insights
Adrenal corticosteroids regulate hippocampal genes via mineralocorticoid (MR) and glucocorticoid receptors (GR). This study identified 203 CORT-responsive genes, revealing distinct MR and GR roles in brain function.
Area of Science:
- Neuroscience
- Molecular Biology
- Genomics
Background:
- Adrenal corticosteroids (CORT) significantly influence hippocampal function.
- Mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) mediate CORT effects by regulating gene expression.
Purpose of the Study:
- To identify CORT-responsive genes in the hippocampus regulated by MR and/or GR using Serial Analysis of Gene Expression (SAGE).
Main Methods:
- Serial Analysis of Gene Expression (SAGE) to profile hippocampal gene expression under varying CORT conditions.
- In situ hybridization to validate gene expression patterns and CORT regulation.
Main Results:
- Identified 203 CORT-responsive genes involved in diverse cellular processes.
- The majority of identified genes were novel.
- MR and GR primarily regulate distinct sets of genes, with limited overlap.
Conclusions:
- The study provides a comprehensive list of novel CORT-responsive hippocampal genes.
- Findings elucidate the molecular basis for differential MR and GR actions on neuronal function, memory, and behavior.