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

Newrzella D, Pahlavan PS, Krüger C, Boehm C, Sorgenfrei O, Schröck H, Eisenhardt G, Bischoff N, Vogt G, Wafzig O, Rossner M, Maurer MH, Hiemisch H, Bach A, Kuschinsky W, Schneider A - BMC Genomics (2007)

Bottom Line: In the ischemic state, only about 100 genes were found to be differentially expressed in CA3 and CA1.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Sygnis Bioscience, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany. Newrzella@Sygnis.de

ABSTRACT

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.

Show MeSH

Related in: MedlinePlus

CA1 and CA3 neurons display a different gene expression repertoire in the native state. Result of the comparison of CA3 and CA1 regions in the native animal. A, We detect 1035 genes that are differentially expressed in the CA3 and CA1 region in sham-treated animals, 566 are significantly enriched in CA3, 487 in CA1 (pfdr < 0.05; differentially regulated genes in red). B, Bar graph showing enrichment factors for the 5 most differentially expressed genes in CA3 and CA1. The enrichment factors reflect relative abundance of gene expression in CA3 over CA1 or vice versa, and were calculated by dividing the mean of the gene abundance in CA3 by CA1 or vice versa. Bok, Bcl-2 related ovarian killer; pvrl3, poliovirus receptor-related 3; rerg, RAS-like, estrogen-regulated; dehal1, Iodotyrosine dehalogenase 1; mpped1, metallophosphoesterase domain containing 1; penk1, preproenkephalin 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2194787&req=5

Figure 2: CA1 and CA3 neurons display a different gene expression repertoire in the native state. Result of the comparison of CA3 and CA1 regions in the native animal. A, We detect 1035 genes that are differentially expressed in the CA3 and CA1 region in sham-treated animals, 566 are significantly enriched in CA3, 487 in CA1 (pfdr < 0.05; differentially regulated genes in red). B, Bar graph showing enrichment factors for the 5 most differentially expressed genes in CA3 and CA1. The enrichment factors reflect relative abundance of gene expression in CA3 over CA1 or vice versa, and were calculated by dividing the mean of the gene abundance in CA3 by CA1 or vice versa. Bok, Bcl-2 related ovarian killer; pvrl3, poliovirus receptor-related 3; rerg, RAS-like, estrogen-regulated; dehal1, Iodotyrosine dehalogenase 1; mpped1, metallophosphoesterase domain containing 1; penk1, preproenkephalin 1.

Mentions: We searched for genes with stronger expression in CA3 or CA1 by direct competitive hybridization of 4 samples each. A total of 1035 genes were found with 566 being stronger expressed in CA3, and 487 in CA1 (Fig. 2A; full list in Additional file 2) (pfdr < 0.05).


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

Newrzella D, Pahlavan PS, Krüger C, Boehm C, Sorgenfrei O, Schröck H, Eisenhardt G, Bischoff N, Vogt G, Wafzig O, Rossner M, Maurer MH, Hiemisch H, Bach A, Kuschinsky W, Schneider A - BMC Genomics (2007)

CA1 and CA3 neurons display a different gene expression repertoire in the native state. Result of the comparison of CA3 and CA1 regions in the native animal. A, We detect 1035 genes that are differentially expressed in the CA3 and CA1 region in sham-treated animals, 566 are significantly enriched in CA3, 487 in CA1 (pfdr < 0.05; differentially regulated genes in red). B, Bar graph showing enrichment factors for the 5 most differentially expressed genes in CA3 and CA1. The enrichment factors reflect relative abundance of gene expression in CA3 over CA1 or vice versa, and were calculated by dividing the mean of the gene abundance in CA3 by CA1 or vice versa. Bok, Bcl-2 related ovarian killer; pvrl3, poliovirus receptor-related 3; rerg, RAS-like, estrogen-regulated; dehal1, Iodotyrosine dehalogenase 1; mpped1, metallophosphoesterase domain containing 1; penk1, preproenkephalin 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2194787&req=5

Figure 2: CA1 and CA3 neurons display a different gene expression repertoire in the native state. Result of the comparison of CA3 and CA1 regions in the native animal. A, We detect 1035 genes that are differentially expressed in the CA3 and CA1 region in sham-treated animals, 566 are significantly enriched in CA3, 487 in CA1 (pfdr < 0.05; differentially regulated genes in red). B, Bar graph showing enrichment factors for the 5 most differentially expressed genes in CA3 and CA1. The enrichment factors reflect relative abundance of gene expression in CA3 over CA1 or vice versa, and were calculated by dividing the mean of the gene abundance in CA3 by CA1 or vice versa. Bok, Bcl-2 related ovarian killer; pvrl3, poliovirus receptor-related 3; rerg, RAS-like, estrogen-regulated; dehal1, Iodotyrosine dehalogenase 1; mpped1, metallophosphoesterase domain containing 1; penk1, preproenkephalin 1.
Mentions: We searched for genes with stronger expression in CA3 or CA1 by direct competitive hybridization of 4 samples each. A total of 1035 genes were found with 566 being stronger expressed in CA3, and 487 in CA1 (Fig. 2A; full list in Additional file 2) (pfdr < 0.05).

Bottom Line: In the ischemic state, only about 100 genes were found to be differentially expressed in CA3 and CA1.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Sygnis Bioscience, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany. Newrzella@Sygnis.de

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus