| 1 | BMC Psychiatry 2007 -1 7: 46 |
|---|---|
| PMID | 17822540 |
| Title | Inflammation-related genes up-regulated in schizophrenia brains. |
| Abstract | Multiple studies have shown that brain gene expression is disturbed in subjects suffering from schizophrenia. However, disentangling disease effects from alterations caused by medication is a challenging task. The main goal of this study is to find transcriptional alterations in schizophrenia that are independent of neuroleptic treatment. We compared the transcriptional profiles in brain autopsy samples from 55 control individuals with that from 55 schizophrenic subjects, subdivided according to the type of antipsychotic medication received. Using global and high-resolution mRNA quantification techniques, we show that genes involved in immune response (GO:0006955) are up regulated in all groups of patients, including those not treated at the time of death. In particular, IFITM2, IFITM3, SERPINA3, and GBP1 showed increased mRNA levels in schizophrenia (p-values from qPCR < or = 0.01). These four genes were co-expressed in both schizophrenic subjects and controls. In-vitro experiments suggest that these genes are expressed in both oligodendrocyte and endothelial cells, where transcription is inducible by the inflammatory cytokines TNF-alpha, IFN-alpha and IFN-gamma. Although the modified genes are not classical indicators of chronic or acute inflammation, our results indicate alterations of inflammation-related pathways in schizophrenia. In addition, the observation in oligodendrocyte cells suggests that alterations in inflammatory-related genes may have consequences for myelination. Our findings encourage future research to explore whether anti-inflammatory agents can be used in combination with traditional antipsychotics for a more efficient treatment of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | BMC Psychiatry 2007 -1 7: 46 |
| PMID | 17822540 |
| Title | Inflammation-related genes up-regulated in schizophrenia brains. |
| Abstract | Multiple studies have shown that brain gene expression is disturbed in subjects suffering from schizophrenia. However, disentangling disease effects from alterations caused by medication is a challenging task. The main goal of this study is to find transcriptional alterations in schizophrenia that are independent of neuroleptic treatment. We compared the transcriptional profiles in brain autopsy samples from 55 control individuals with that from 55 schizophrenic subjects, subdivided according to the type of antipsychotic medication received. Using global and high-resolution mRNA quantification techniques, we show that genes involved in immune response (GO:0006955) are up regulated in all groups of patients, including those not treated at the time of death. In particular, IFITM2, IFITM3, SERPINA3, and GBP1 showed increased mRNA levels in schizophrenia (p-values from qPCR < or = 0.01). These four genes were co-expressed in both schizophrenic subjects and controls. In-vitro experiments suggest that these genes are expressed in both oligodendrocyte and endothelial cells, where transcription is inducible by the inflammatory cytokines TNF-alpha, IFN-alpha and IFN-gamma. Although the modified genes are not classical indicators of chronic or acute inflammation, our results indicate alterations of inflammation-related pathways in schizophrenia. In addition, the observation in oligodendrocyte cells suggests that alterations in inflammatory-related genes may have consequences for myelination. Our findings encourage future research to explore whether anti-inflammatory agents can be used in combination with traditional antipsychotics for a more efficient treatment of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | PLoS ONE 2010 -1 5: -1 |
| PMID | 20927331 |
| Title | QKI-7 regulates expression of interferon-related genes in human astrocyte glioma cells. |
| Abstract | The human QKI gene, called quaking homolog, KH domain RNA binding (mouse), is a candidate gene for schizophrenia encoding an RNA-binding protein. This gene was shown to be essential for myelination in oligodendrocytes. QKI is also highly expressed in astrocytes, but its function in these cells is not known. We studied the effect of small interference RNA (siRNA)-mediated QKI depletion on global gene expression in human astrocyte glioma cells. Microarray measurements were confirmed with real-time quantitative polymerase chain reaction (qPCR). The presence of QKI binding sites (QRE) was assessed by a bioinformatic approach. Viability and cell morphology were also studied. The most significant alteration after QKI silencing was the decreased expression of genes involved in interferon (IFN) induction (P = 6.3E-10), including IFIT1, IFIT2, MX1, MX2, G1P2, G1P3, GBP1 and IFIH1. All eight genes were down-regulated after silencing of the splice variant QKI-7, but were not affected by QKI-5 silencing. Interestingly, four of them were up-regulated after treatment with the antipsychotic agent haloperidol that also resulted in increased QKI-7 mRNA levels. The coordinated expression of QKI-7 splice variant and IFN-related genes supports the idea that this particular splice variant has specific functions in astrocytes. Furthermore, a role of QKI-7 as a regulator of an inflammatory gene pathway in astrocytes is suggested. This hypothesis is well in line with growing experimental evidence on the role of inflammatory components in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |