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Expression of the rap1 guanine nucleotide exchange factor, MR-GEF, is altered in individuals with bipolar disorder

Title: Expression of the rap1 guanine nucleotide exchange factor, MR-GEF, is altered in individuals with bipolar disorder
Authors: Bithell, A; Hsu, T; Kandanearatchi, A; Landau, S; Everall, IP; Tsuang, MT; Chana, G; Williams, BP
Contributors: Domschke, K
Publisher Information: PUBLIC LIBRARY SCIENCE
Publication Year: 2010
Collection: The University of Melbourne: Digital Repository
Description: In the rodent forebrain GABAergic neurons are generated from progenitor cells that express the transcription factors Dlx1 and Dlx2. The Rap-1 guanine nucleotide exchange factor, MR-GEF, is turned on by many of these developing GABAergic neurons. Expression of both Dlx1/2 and MR-GEF is retained in both adult mouse and human forebrain where, in human, decreased Dlx1 expression has been associated with psychosis. Using in situ hybridization studies we show that MR-GEF expression is significantly down-regulated in the forebrain of Dlx1/2 double mutant mice suggesting that MR-GEF and Dlx1/2 form part of a common signalling pathway during GABAergic neuronal development. We therefore compared MR-GEF expression by in situ hybridization in individuals with major psychiatric disorders (schizophrenia, bipolar disorder, major depression) and control individuals. We observed a significant positive correlation between layers II and IV of the dorso-lateral prefrontal cortex (DLPFC) in the percentage of MR-GEF expressing neurons in individuals with bipolar disorder, but not in individuals with schizophrenia, major depressive disorder or in controls. Since MR-GEF encodes a Rap1 GEF able to activate G-protein signalling, we suggest that changes in MR-GEF expression could potentially influence neurotransmission.
Document Type: article in journal/newspaper
Language: English
ISSN: 1932-6203
Relation: https://hdl.handle.net/11343/264317
Availability: https://hdl.handle.net/11343/264317
Rights: https://creativecommons.org/licenses/by/4.0 ; CC BY
Accession Number: edsbas.EB7B7F05
Database: BASE