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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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Quantitative real-time (qRT)-PCR validation of RNA-Seq results. Expression levels of selective. Genes related to immune/inflammation were measured by quantitative RT-PCR. #P<0.1, *P<0.05, **P<0.005, ***P<0.0001.
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fig2: Quantitative real-time (qRT)-PCR validation of RNA-Seq results. Expression levels of selective. Genes related to immune/inflammation were measured by quantitative RT-PCR. #P<0.1, *P<0.05, **P<0.005, ***P<0.0001.

Mentions: We validated the differential expression of seven genes from our RNA-Seq results using qRT-PCR. To gain adequate detection power, we included additional samples from the Array Collection for the qRT-PCR validation. Confounding effects of demographic and clinical variables were examined. RIN was significantly correlated with expression levels of the seven genes and brain pH was additionally correlated with APOL1 (All P<0.05). Body mass index was correlated with expression level of ADORA2A and smoking was associated with expression level of CD163 and IFITM3. Analysis of covariance revealed that ADORA2A, APOL1, IGFBP4, IFITM1, IFITM2 and IFITM3 mRNA levels were significantly increased in schizophrenia (Figure 2, All P<0.05), which is consistent with the RNA-Seq results. Expression of CD163 mRNA was increased in schizophrenia at trend level (Figures 2, P=0.09).


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)

Quantitative real-time (qRT)-PCR validation of RNA-Seq results. Expression levels of selective. Genes related to immune/inflammation were measured by quantitative RT-PCR. #P<0.1, *P<0.05, **P<0.005, ***P<0.0001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Quantitative real-time (qRT)-PCR validation of RNA-Seq results. Expression levels of selective. Genes related to immune/inflammation were measured by quantitative RT-PCR. #P<0.1, *P<0.05, **P<0.005, ***P<0.0001.
Mentions: We validated the differential expression of seven genes from our RNA-Seq results using qRT-PCR. To gain adequate detection power, we included additional samples from the Array Collection for the qRT-PCR validation. Confounding effects of demographic and clinical variables were examined. RIN was significantly correlated with expression levels of the seven genes and brain pH was additionally correlated with APOL1 (All P<0.05). Body mass index was correlated with expression level of ADORA2A and smoking was associated with expression level of CD163 and IFITM3. Analysis of covariance revealed that ADORA2A, APOL1, IGFBP4, IFITM1, IFITM2 and IFITM3 mRNA levels were significantly increased in schizophrenia (Figure 2, All P<0.05), which is consistent with the RNA-Seq results. Expression of CD163 mRNA was increased in schizophrenia at trend level (Figures 2, P=0.09).

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