期刊
BIOLOGICAL PSYCHIATRY
卷 62, 期 7, 页码 711-721出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2006.12.021
关键词
DNA; heat-shock protein; immune system; microarray; postmortem brain; prefrontal cortex; qPCR; schizophrenia
资金
- NICHD NIH HHS [P30 HD015052] Funding Source: Medline
- NIMH NIH HHS [P50 MH045156, R01 MH067234-05, 2P50 MH45156, K02 MH070786-04, R01 MH067234, K02 MH070786, R01 MH079299-01, R01 MH079299] Funding Source: Medline
Background: Schizophrenia is characterized by complex gene expression changes. The transcriptome alterations in the prefrontal cortex have been the subject of several recent postmortem studies that yielded both convergent and divergent findings. Methods: To increase measurement precision, we used a custom-designed DNA microarray platform with long oligonucleotides and multiple probes with replicates. The platform was designed to assess the expression of > 1800 genes specifically chosen because of their hypothesized roles in the pathophysiology of schizophrenia. The gene expression differences in dorsolateral prefrontal cortex samples from 14 matched pairs of schizophrenia and control subjects were analyzed with two technical replicates and four data mining approaches. Results: In addition to replicating many expression changes in synaptic, oligodendrocyte, and signal transduction genes, we uncovered and validated a robust immune/chaperone transcript upregulation in the schizophrenia samples. Conclusions: We speculate that the overexpression of SERPINA3, IFITM1, IFITM2, IFITM3, CHI3L1, MT2A, CD14, HSPB1, HSPA1B, and HSPA1A in schizophrenia subjects represents a long-lasting and correlated signature of an early environmental insult during development that actively contributes to the pathophysiology of prefrontal dysfunction.
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