Factors involved in gene expression regulation of g-protein coupled receptors and related signaling pathway genes in mood disorder

H. Tomita; H. Kim; P.V. Choudary; S.J. Evans; J. Li; M.P. Vawter; D.M. Walsh; M.E. Atz; L. Shao; K.M. Overman; F. Meng; C.R. Neal; J.D.H. Stead; R.M. Myers; E.G. Jones; S.J. Watson; H. Akil; W.E. Bunney
Society for Neuroscience annual meeting. 2005.


Evidence supports that altered G protein coupled receptors and their intracellular down stream signaling events, such as cAMP and phosphatidylinositol signaling pathways, are involved in the pathogeneses of bipolar disorder (BPD) and major depressive disorder (MDD). Based on our microarray analysis in postmortem brain (anterior cingulate cortex (AnCg), dorsolateral prefrontal cortex, amygdala, hippocampus, nucleus accumbens and cerebellum) from patients with BPD and MDD, we observed that mRNA expression of certain GPCRs, and genes involved in the GPCR related signaling pathways were dysregulated. The most consistent findings among GPCR genes throughout our experiments were observed in two orphan GPCR gene mRNAs, GPRC5B and GPR37, both of which were increased in AnCg and significantly decreased in all 6 brain regions analyzed. We have confirmed these findings were not overlapped with genes dysregulated in lithium treated animals. We also discuss factors which might affect these dysregulation in gene expression, including polymorphism and methylation status in the promoter region, as well as effect of transcription factors. Support Contributed By: Pritzker Family Philanthropic Foundation, NIH Conte Center Grant P50 MH60398. We thank contributions of R. Stein, K. Burke, C. Cervantes, K. Lopez.