Infragranular gene expression disturbances in the prefrontal cortex in schizophrenia: Signature of altered neural development?

Neurobiology of Disease

David A. Lewis¹  Szatmár Horváth²  Dominique Arion³  Károly Mirnics³ 

[1] Department of Psychiatry, University of Szeged, Hungary;Department of Psychiatry and Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN 27323, USA;Department of Psychiatry, U of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA;

关键词: DNA microarray;    Gene expression;    Cortical layers;    Laser dissection;    Postmortem;    Neocortex;   

DOI  :  

来源: DOAJ

【 摘 要 】

The development of the human neocortex gives rise to a complex cytoarchitecture, grouping together cells with similar structure, connectivity and function. As a result, the six neocortical laminae show distinct molecular content. In schizophrenia, many anatomical and neurochemical changes appear to be restricted to a subset of lamina and/or cell types. In this study, we hypothesized that supragranular (SG; laminae II–III) and infragranular layers (IG; laminae V–VI) of area 46 in the human prefrontal cortex will show distinct and specific transcriptome alterations between subjects with schizophrenia and matched controls. To enhance sample homogeneity, we compared the gene expression patterns of the SG and IG layers of 8 matched middle-aged male subjects with schizophrenia to 8 pairwise matched controls using two replicate DNA microarrays for each sample. The study revealed strong disease-related laminar expression differences between the SG and IG layers. Expression changes were dominated by an overall underexpression of the IG-enriched genes in the schizophrenia subjects compared to normal control subjects. Furthermore, using a diagnosis-blind, unsupervised clustering of the control-derived SG or IG-enriched transcripts, the IG-enriched markers segregated the subjects with schizophrenia from the matched controls with a high degree of confidence. Importantly, multiple members of the semaphorin gene family reported altered gene expression, suggesting that the IG gene expression disturbances in subjects with schizophrenia may be a result of altered cortical development and disrupted brain connectivity.

【 授权许可】

Unknown