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Gene expression profiling by mRNA sequencing reveals increased expression of immune/inflammation-related genes in the hippocampus of individuals with schizophrenia.

Hwang Y, Kim J, Shin JY, Kim JI, Seo JS, Webster MJ, Lee D, Kim S - Transl Psychiatry (2013)

Bottom Line: Now using RNA-Seq data from the hippocampus, we have identified 144 differentially expressed genes in schizophrenia cases as compared with unaffected controls.Immune/inflammation response was the main biological process over-represented in these genes.The results indicate that abnormal immune/inflammation response in the hippocampus may underlie the pathophysiology of schizophrenia and may be associated with abnormalities in the parvalbumin-containing neurons that lead to the cognitive deficits of the disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, Korea.

ABSTRACT
Whole-genome expression profiling in postmortem brain tissue has recently provided insight into the pathophysiology of schizophrenia. Previous microarray and RNA-Seq studies identified several biological processes including synaptic function, mitochondrial function and immune/inflammation response as altered in the cortex of subjects with schizophrenia. Now using RNA-Seq data from the hippocampus, we have identified 144 differentially expressed genes in schizophrenia cases as compared with unaffected controls. Immune/inflammation response was the main biological process over-represented in these genes. The upregulation of several of these genes, IFITM1, IFITM2, IFITM3, APOL1 (Apolipoprotein L1), ADORA2A (adenosine receptor 2A), IGFBP4 and CD163 were validated in the schizophrenia subjects using data from the SNCID database and with quantitative RT-PCR. We identified a co-expression module associated with schizophrenia that includes the majority of differentially expressed genes related to immune/inflammation response as well as with the density of parvalbumin-containing neurons in the hippocampus. The results indicate that abnormal immune/inflammation response in the hippocampus may underlie the pathophysiology of schizophrenia and may be associated with abnormalities in the parvalbumin-containing neurons that lead to the cognitive deficits of the disease.

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Co-expression network analysis in the hippocampus. The co-expression module (M19), which is significantly associated with schizophrenia in the hippocampus (a) and major biological processes (Gene ontology) over-represented in the genes in the co-expression module (b). The top 150 network connections with topological overlap above the threshold of 0.03 were visualized using VisANT.32 Differentially expressed genes are blue.
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fig4: Co-expression network analysis in the hippocampus. The co-expression module (M19), which is significantly associated with schizophrenia in the hippocampus (a) and major biological processes (Gene ontology) over-represented in the genes in the co-expression module (b). The top 150 network connections with topological overlap above the threshold of 0.03 were visualized using VisANT.32 Differentially expressed genes are blue.

Mentions: To identify altered biological processes in the hippocampus of schizophrenia, we conducted unsupervised gene co-expression network analyses using the normalized RNA-Seq data from both the schizophrenia and control groups. A total of 23 co-expression modules were generated and five modules were significantly associated with schizophrenia (Supplementary Table 5). However, three modules were excluded from downstream analysis because they were also significantly correlated with RIN. Module 3 (M3) was a large module consisting of 632 genes (Figure 3a). Ubiquitination, chromatin modification and protein localization were significantly enriched in the genes of this module (Figure 3b and Supplementary Figure 1). M19 was also a large module and included mainly the differentially expressed genes (Figure 4a). The I-kappa B/NF-kappa B cascade, cell-mediated immune response and inflammation were significantly enriched in the module (Figure 4b and Supplementary Figure 2). Immune-related genes such as S100A8, S100A9, IFITM2 and IFITM3 were included in the module.


Gene expression profiling by mRNA sequencing reveals increased expression of immune/inflammation-related genes in the hippocampus of individuals with schizophrenia.

Hwang Y, Kim J, Shin JY, Kim JI, Seo JS, Webster MJ, Lee D, Kim S - Transl Psychiatry (2013)

Co-expression network analysis in the hippocampus. The co-expression module (M19), which is significantly associated with schizophrenia in the hippocampus (a) and major biological processes (Gene ontology) over-represented in the genes in the co-expression module (b). The top 150 network connections with topological overlap above the threshold of 0.03 were visualized using VisANT.32 Differentially expressed genes are blue.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3818014&req=5

fig4: Co-expression network analysis in the hippocampus. The co-expression module (M19), which is significantly associated with schizophrenia in the hippocampus (a) and major biological processes (Gene ontology) over-represented in the genes in the co-expression module (b). The top 150 network connections with topological overlap above the threshold of 0.03 were visualized using VisANT.32 Differentially expressed genes are blue.
Mentions: To identify altered biological processes in the hippocampus of schizophrenia, we conducted unsupervised gene co-expression network analyses using the normalized RNA-Seq data from both the schizophrenia and control groups. A total of 23 co-expression modules were generated and five modules were significantly associated with schizophrenia (Supplementary Table 5). However, three modules were excluded from downstream analysis because they were also significantly correlated with RIN. Module 3 (M3) was a large module consisting of 632 genes (Figure 3a). Ubiquitination, chromatin modification and protein localization were significantly enriched in the genes of this module (Figure 3b and Supplementary Figure 1). M19 was also a large module and included mainly the differentially expressed genes (Figure 4a). The I-kappa B/NF-kappa B cascade, cell-mediated immune response and inflammation were significantly enriched in the module (Figure 4b and Supplementary Figure 2). Immune-related genes such as S100A8, S100A9, IFITM2 and IFITM3 were included in the module.

Bottom Line: Now using RNA-Seq data from the hippocampus, we have identified 144 differentially expressed genes in schizophrenia cases as compared with unaffected controls.Immune/inflammation response was the main biological process over-represented in these genes.The results indicate that abnormal immune/inflammation response in the hippocampus may underlie the pathophysiology of schizophrenia and may be associated with abnormalities in the parvalbumin-containing neurons that lead to the cognitive deficits of the disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, Korea.

ABSTRACT
Whole-genome expression profiling in postmortem brain tissue has recently provided insight into the pathophysiology of schizophrenia. Previous microarray and RNA-Seq studies identified several biological processes including synaptic function, mitochondrial function and immune/inflammation response as altered in the cortex of subjects with schizophrenia. Now using RNA-Seq data from the hippocampus, we have identified 144 differentially expressed genes in schizophrenia cases as compared with unaffected controls. Immune/inflammation response was the main biological process over-represented in these genes. The upregulation of several of these genes, IFITM1, IFITM2, IFITM3, APOL1 (Apolipoprotein L1), ADORA2A (adenosine receptor 2A), IGFBP4 and CD163 were validated in the schizophrenia subjects using data from the SNCID database and with quantitative RT-PCR. We identified a co-expression module associated with schizophrenia that includes the majority of differentially expressed genes related to immune/inflammation response as well as with the density of parvalbumin-containing neurons in the hippocampus. The results indicate that abnormal immune/inflammation response in the hippocampus may underlie the pathophysiology of schizophrenia and may be associated with abnormalities in the parvalbumin-containing neurons that lead to the cognitive deficits of the disease.

Show MeSH
Related in: MedlinePlus