Expression of the Rap1 guanine nucleotide exchange factor, MR-GEF, is altered in individuals with bipolar disorder.
Expression of the Rap1 guanine nucleotide exchange factor, MR-GEF, is altered in individuals with bipolar disorder.
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DOI：
10.1371/journal.pone.0010392
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发表时间：
2010-04-28
期刊：
影响因子：
3.7
通讯作者：
Williams BP
中科院分区：
文献类型：
--
作者：
Bithell A;Hsu T;Kandanearatchi A;Landau S;Everall IP;Tsuang MT;Chana G;Williams BP
在啮齿动物的前脑中，GABA能神经元是由表达转录因子Dlx1和Dlx2的祖细胞产生的。许多发育中的GABA能神经元激活Rap-1鸟嘌呤核苷酸交换因子。在成年小鼠和人类的前脑中都保留了Dlx1/2和MR-gef的表达，而在人类中，Dlx1的表达降低与精神病有关。通过原位杂交研究，我们发现在Dlx1/2双突变小鼠的前脑中，MR-gef的表达显着下调，这表明在GABA能神经元发育过程中，mr-gef和Dlx1/2形成了共同的信号通路的一部分。因此，我们通过原位杂交比较了患有严重精神障碍(精神分裂症、双相情感障碍、严重抑郁症)的个体和对照个体中MR-egf的表达。我们观察到双相情感障碍患者前额叶背外侧皮质(DLPFC)第II层和第IV层MR-gef表达神经元的百分比呈显著正相关，而在精神分裂症、重度抑郁障碍患者和对照组中则无相关关系。由于MR-全环基金编码了能够激活G-蛋白信号的Rap1全环基金，我们认为，全环基金表达的变化可能会潜在地影响神经传递。
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.
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影响因子：
3.3
作者：
Benes, FM;Vincent, SL;Khan, Y
通讯作者：
Khan, Y
影响因子：
5.3
作者：
Brill, Monika S.;Snapyan, Marina;Goetz, Magdalena
通讯作者：
Goetz, Magdalena
影响因子：
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作者：
Kromkamp, M;Uylings, HBM;Kahn, RS
通讯作者：
Kahn, RS
DOI：
10.1615/critrevneurobiol.v16.i12.10
发表时间：
2004-01-01
期刊：
Critical Reviews in Neurobiology
影响因子：
--
作者：
Costa, E.;Davis, J. M.;Veldic, M.
通讯作者：
Veldic, M.
DOI：
10.1016/j.devbrainres.2003.09.017
发表时间：
2003-12-19
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Bithell, A;Alberta, J;Williams, BP
通讯作者：
Williams, BP