NDLI: Regulation of the GABA cell phenotype in hippocampus of schizophrenics and bipolars

Content Provider	PubMed Central
Author	Benes, Francine M. Lim, Benjamin David, Matzilevich Walsh, John P. Sivan, Subburaju Minns, Martin
Copyright Year	2007
Abstract	GABAergic dysfunction is present in the hippocampus in schizophrenia (SZ) and bipolar disorder (BD). The trisynaptic pathway was “deconstructed” into various layers of sectors CA3/2 and CA1 and gene expression profiling performed. Network association analysis was used to uncover genes that may be related to regulation of glutamate decarboxylase 67 (GAD67), a marker for this system that has been found by many studies to show decreased expression in SZs and BDs. The most striking change was a down-regulation of GAD67 in the stratum oriens (SO) of CA2/3 in both groups; CA1 only showed changes in the SO of schizophrenics. The network generated for GAD67 contained 25 genes involved in the regulation of kainate receptors, TGF-β and Wnt signaling, as well as transcription factors involved in cell growth and differentiation. In SZs, IL-1β, (GRIK2/3), TGF-β2, TGF-βR1, histone deacetylase 1 (HDAC1), death associated protein (DAXX), and cyclin D2 (CCND2) were all significantly up-regulated, whereas in BDs, PAX5, Runx2, LEF1, TLE1, and CCND2 were significantly down-regulated. In the SO of CA1 of BDs, where GAD67 showed no expression change, TGF-β and Wnt signaling genes were all up-regulated, but other transcription factors showed no change in expression. In other layers/sectors, BDs showed no expression changes in these GAD67 network genes. Overall, these results are consistent with the hypothesis that decreased expression of GAD67 may be associated with an epigenetic mechanism in SZ. In BD, however, a suppression of transcription factors involved in cell differentiation may contribute to GABA dysfunction.
Related Links	http://dx.doi.org/10.1073/pnas.0703806104
Starting Page	10164
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	24
Volume Number	104
Language	English
Publisher	National Academy of Sciences
Publisher Date	2007-06-12
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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