| Gene expression analysis in the hippocampal formation of tree shrews chronically treated with cortisol. | |
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MedLine Citation:
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PMID: 15505804 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Adrenal corticosteroids influence the function of the hippocampus, the brain structure in which the highest expression of glucocorticoid receptors is found. Chronic high levels of cortisol elicited by stress or through exogenous administration can cause irreversible damage and cognitive deficits. In this study, we searched for genes expressed in the hippocampal formation after chronic cortisol treatment in male tree shrews. Animals were treated orally with cortisol for 28 days. At the end of the experiments, we generated two subtractive hippocampal hybridization libraries from which we sequenced 2,246 expressed sequenced tags (ESTs) potentially regulated by cortisol. To validate this approach further, we selected some of the candidate clones to measure mRNA expression levels in hippocampus using real-time PCR. We found that 66% of the sequences tested (10 of 15) were differentially represented between cortisol-treated and control animals. The complete set of clones was subjected to a bioinformatic analysis, which allowed classification of the ESTs into four different main categories: 1) known proteins or genes (approximately 28%), 2) ESTs previously published in the database (approximately 16%), 3) novel ESTs matching only the reference human or mouse genome (approximately 5%), and 4) sequences that do not match any public database (50%). Interestingly, the last category was the most abundant. Hybridization assays revealed that several of these clones are indeed expressed in hippocampal tissue from tree shrew, human, and/or rat. Therefore, we discovered an extensive inventory of new molecular targets in the hippocampus that serves as a reference for hippocampal transcriptional responses under various conditions. Finally, a detailed analysis of the genomic localization in human and mouse genomes revealed a survey of putative novel splicing variants for several genes of the nervous system. |
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Authors:
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Julieta Alfonso; Fernán Agüero; Daniel O Sanchez; Gabriele Flugge; Eberhard Fuchs; Alberto C C Frasch; Guido D Pollevick |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of neuroscience research Volume: 78 ISSN: 0360-4012 ISO Abbreviation: J. Neurosci. Res. Publication Date: 2004 Dec |
Date Detail:
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Created Date: 2004-11-30 Completed Date: 2005-02-28 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7600111 Medline TA: J Neurosci Res Country: United States |
Other Details:
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Languages: eng Pagination: 702-10 Citation Subset: IM |
Affiliation:
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Instituto de Investigaciones Biotecnológicas, Instituto Tecnológico de Chascomús-CONICET, Universidad Nacional de General San Martín, San Martín, Argentina. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cloning, Molecular / methods Drug Administration Schedule Expressed Sequence Tags Gene Expression / drug effects* Gene Expression Profiling / methods Gene Expression Regulation / drug effects* Gene Library Hippocampus / drug effects*, physiology Humans Hydrocortisone / administration & dosage* In Situ Hybridization / methods Male RNA, Messenger / biosynthesis Rats Reverse Transcriptase Polymerase Chain Reaction / methods Tupaiidae |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 50-23-7/Hydrocortisone |
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