| First Author | Bithell A | Year | 2010 |
| Journal | PLoS One | Volume | 5 |
| Issue | 4 | Pages | e10392 |
| PubMed ID | 20436929 | Mgi Jnum | J:160574 |
| Mgi Id | MGI:4454629 | Doi | 10.1371/journal.pone.0010392 |
| Citation | Bithell A, et al. (2010) Expression of the Rap1 guanine nucleotide exchange factor, MR-GEF, is altered in individuals with bipolar disorder. PLoS One 5(4):e10392 |
| abstractText | 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. |
