GENE EXPRESSION PROFILES OF G-PROTEIN SIGNALING PATHWAY RELATED GENES IN POSTMORTEM BRAINS OF MOOD DISORDER PATIENTS

H. Tomita; M.P. Vawter; L. Shao; M.E. Atz; K.M. Overman; F. Meng; C.R. Neal; J.D.H. Stead; S.J. Evans; P.V. Choudary; J. Li; B.M. Bolstad; P. Cartagena; D.M. Walsh; T.P. Speed; R.M. Myers; E.G. Jones; S.J. Watson; H. Akil; W.E. Bunney
Society for Neuroscience 34th Annual Meeting. 2004.

Abstract

Evidence supports that altered G protein coupled receptors related neurotransmitter systems (including monoamines and neuropeptides) and their intracellular down stream signaling events (such as cAMP, phosphatidylinositol, and mitogen-activated protein kinase (MAPK) signaling pathways) are involved in the pathogeneses of mood disorders. Based on microarray data in patients with bipolar disorder type I (BPD, n = 11), major depression (MDD, n=18), and control (n=18), we discuss gene expression patterns related to G protein signaling pathways in the context of pathogeneses of the mood disorders, suicidal behavior and drug prescription. Total RNA was extracted from anterior cingulate, dorsolateral prefrontal cortices, and each sample was run in duplicate on Affymetrix U133A and U133B chips. Data for each brain region were analyzed using fitPLM employing subject as a factor. Selected microarray findings were validated by quantitative RT-PCR. We observed gene expression patterns unique to BPD and MDD in genes relevant to neuropeptide neurotransmission, phosphatidylinositol and MAPK signaling pathways. We also discuss expression pattern of G protein signaling pathways in additional brain regions, including hippocampus and amygdala. 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.