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The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia

BACKGROUND: The different physiological repertoire of CA3 and CA1 neurons in the hippocampus, as well as their differing behaviour after noxious stimuli are ultimately based upon differences in the expressed genome. We have compared CA3 and CA1 gene expression in the uninjured brain, and after cereb...

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Autores principales: Newrzella, Dieter, Pahlavan, Payam S, Krüger, Carola, Boehm, Christine, Sorgenfrei, Oliver, Schröck, Helmut, Eisenhardt, Gisela, Bischoff, Nadine, Vogt, Gerhard, Wafzig, Oliver, Rossner, Moritz, Maurer, Martin H, Hiemisch, Holger, Bach, Alfred, Kuschinsky, Wolfgang, Schneider, Armin
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194787/
https://www.ncbi.nlm.nih.gov/pubmed/17937787
http://dx.doi.org/10.1186/1471-2164-8-370
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author Newrzella, Dieter
Pahlavan, Payam S
Krüger, Carola
Boehm, Christine
Sorgenfrei, Oliver
Schröck, Helmut
Eisenhardt, Gisela
Bischoff, Nadine
Vogt, Gerhard
Wafzig, Oliver
Rossner, Moritz
Maurer, Martin H
Hiemisch, Holger
Bach, Alfred
Kuschinsky, Wolfgang
Schneider, Armin
author_facet Newrzella, Dieter
Pahlavan, Payam S
Krüger, Carola
Boehm, Christine
Sorgenfrei, Oliver
Schröck, Helmut
Eisenhardt, Gisela
Bischoff, Nadine
Vogt, Gerhard
Wafzig, Oliver
Rossner, Moritz
Maurer, Martin H
Hiemisch, Holger
Bach, Alfred
Kuschinsky, Wolfgang
Schneider, Armin
author_sort Newrzella, Dieter
collection PubMed
description BACKGROUND: The different physiological repertoire of CA3 and CA1 neurons in the hippocampus, as well as their differing behaviour after noxious stimuli are ultimately based upon differences in the expressed genome. We have compared CA3 and CA1 gene expression in the uninjured brain, and after cerebral ischemia using laser microdissection (LMD), RNA amplification, and array hybridization. RESULTS: Profiling in CA1 vs. CA3 under normoxic conditions detected more than 1000 differentially expressed genes that belong to different, physiologically relevant gene ontology groups in both cell types. The comparison of each region under normoxic and ischemic conditions revealed more than 5000 ischemia-regulated genes for each individual cell type. Surprisingly, there was a high co-regulation in both regions. In the ischemic state, only about 100 genes were found to be differentially expressed in CA3 and CA1. The majority of these genes were also different in the native state. A minority of interesting genes (e.g. inhibinbetaA) displayed divergent expression preference under native and ischemic conditions with partially opposing directions of regulation in both cell types. CONCLUSION: The differences found in two morphologically very similar cell types situated next to each other in the CNS are large providing a rational basis for physiological differences. Unexpectedly, the genomic response to ischemia is highly similar in these two neuron types, leading to a substantial attenuation of functional genomic differences in these two cell types. Also, the majority of changes that exist in the ischemic state are not generated de novo by the ischemic stimulus, but are preexistant from the genomic repertoire in the native situation. This unexpected influence of a strong noxious stimulus on cell-specific gene expression differences can be explained by the activation of a cell-type independent conserved gene-expression program. Our data generate both novel insights into the relation of the quiescent and stimulus-induced transcriptome in different cells, and provide a large dataset to the research community, both for mapping purposes, as well as for physiological and pathophysiological research.
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spelling pubmed-21947872008-01-13 The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia Newrzella, Dieter Pahlavan, Payam S Krüger, Carola Boehm, Christine Sorgenfrei, Oliver Schröck, Helmut Eisenhardt, Gisela Bischoff, Nadine Vogt, Gerhard Wafzig, Oliver Rossner, Moritz Maurer, Martin H Hiemisch, Holger Bach, Alfred Kuschinsky, Wolfgang Schneider, Armin BMC Genomics Research Article BACKGROUND: The different physiological repertoire of CA3 and CA1 neurons in the hippocampus, as well as their differing behaviour after noxious stimuli are ultimately based upon differences in the expressed genome. We have compared CA3 and CA1 gene expression in the uninjured brain, and after cerebral ischemia using laser microdissection (LMD), RNA amplification, and array hybridization. RESULTS: Profiling in CA1 vs. CA3 under normoxic conditions detected more than 1000 differentially expressed genes that belong to different, physiologically relevant gene ontology groups in both cell types. The comparison of each region under normoxic and ischemic conditions revealed more than 5000 ischemia-regulated genes for each individual cell type. Surprisingly, there was a high co-regulation in both regions. In the ischemic state, only about 100 genes were found to be differentially expressed in CA3 and CA1. The majority of these genes were also different in the native state. A minority of interesting genes (e.g. inhibinbetaA) displayed divergent expression preference under native and ischemic conditions with partially opposing directions of regulation in both cell types. CONCLUSION: The differences found in two morphologically very similar cell types situated next to each other in the CNS are large providing a rational basis for physiological differences. Unexpectedly, the genomic response to ischemia is highly similar in these two neuron types, leading to a substantial attenuation of functional genomic differences in these two cell types. Also, the majority of changes that exist in the ischemic state are not generated de novo by the ischemic stimulus, but are preexistant from the genomic repertoire in the native situation. This unexpected influence of a strong noxious stimulus on cell-specific gene expression differences can be explained by the activation of a cell-type independent conserved gene-expression program. Our data generate both novel insights into the relation of the quiescent and stimulus-induced transcriptome in different cells, and provide a large dataset to the research community, both for mapping purposes, as well as for physiological and pathophysiological research. BioMed Central 2007-10-15 /pmc/articles/PMC2194787/ /pubmed/17937787 http://dx.doi.org/10.1186/1471-2164-8-370 Text en Copyright © 2007 Newrzella et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Newrzella, Dieter
Pahlavan, Payam S
Krüger, Carola
Boehm, Christine
Sorgenfrei, Oliver
Schröck, Helmut
Eisenhardt, Gisela
Bischoff, Nadine
Vogt, Gerhard
Wafzig, Oliver
Rossner, Moritz
Maurer, Martin H
Hiemisch, Holger
Bach, Alfred
Kuschinsky, Wolfgang
Schneider, Armin
The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia
title The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia
title_full The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia
title_fullStr The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia
title_full_unstemmed The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia
title_short The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia
title_sort functional genome of ca1 and ca3 neurons under native conditions and in response to ischemia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194787/
https://www.ncbi.nlm.nih.gov/pubmed/17937787
http://dx.doi.org/10.1186/1471-2164-8-370
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