Dataset Information

G protein-linked signaling pathways in bipolar and major depressive disorders.

ABSTRACT: The G-protein linked signaling system (GPLS) comprises a large number of G-proteins, G protein-coupled receptors (GPCRs), GPCR ligands, and downstream effector molecules. G-proteins interact with both GPCRs and downstream effectors such as cyclic adenosine monophosphate (cAMP), phosphatidylinositols, and ion channels. The GPLS is implicated in the pathophysiology and pharmacology of both major depressive disorder (MDD) and bipolar disorder (BPD). This study evaluated whether GPLS is altered at the transcript level. The gene expression in the dorsolateral prefrontal (DLPFC) and anterior cingulate (ACC) were compared from MDD, BPD, and control subjects using Affymetrix Gene Chips and real time quantitative PCR. High quality brain tissue was used in the study to control for confounding effects of agonal events, tissue pH, RNA integrity, gender, and age. GPLS signaling transcripts were altered especially in the ACC of BPD and MDD subjects. Transcript levels of molecules which repress cAMP activity were increased in BPD and decreased in MDD. Two orphan GPCRs, GPRC5B and GPR37, showed significantly decreased expression levels in MDD, and significantly increased expression levels in BPD. Our results suggest opposite changes in BPD and MDD in the GPLS, "activated" cAMP signaling activity in BPD and "blunted" cAMP signaling activity in MDD. GPRC5B and GPR37 both appear to have behavioral effects, and are also candidate genes for neurodegenerative disorders. In the context of the opposite changes observed in BPD and MDD, these GPCRs warrant further study of their brain effects.

SUBMITTER: Tomita H

PROVIDER: S-EPMC3870297 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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G protein-linked signaling pathways in bipolar and major depressive disorders.

Tomita Hiroaki H Ziegler Mary E ME Kim Helen B HB Evans Simon J SJ Choudary Prabhakara V PV Li Jun Z JZ Meng Fan F Dai Manhong M Myers Richard M RM Neal Charles R CR Speed Terry P TP Barchas Jack D JD Schatzberg Alan F AF Watson Stanley J SJ Akil Huda H Jones Edward G EG Bunney William E WE Vawter Marquis P MP

Frontiers in genetics 20131223

The G-protein linked signaling system (GPLS) comprises a large number of G-proteins, G protein-coupled receptors (GPCRs), GPCR ligands, and downstream effector molecules. G-proteins interact with both GPCRs and downstream effectors such as cyclic adenosine monophosphate (cAMP), phosphatidylinositols, and ion channels. The GPLS is implicated in the pathophysiology and pharmacology of both major depressive disorder (MDD) and bipolar disorder (BPD). This study evaluated whether GPLS is altered at t ...[more]

PMID: 24391664

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Project description:The prevalence of ankylosing spondylitis (AS) and major depressive disorders (MDD) becomes increasingly pronounced, exerting a significant impact on the life quality of contemporary people. Although there is mounting evidence of a link between AS and major depression disorders, the specific interactions between the two have not been thoroughly investigated. To this end, this study aimed to check whether the gene expression profiles of patients with AS and major depression disorders overlapped, and whether there were any functional links between the identified genes via protein-protein interactions. Herein, the relationship between the 4 datasets (GSE73754, GSE98793, GSE25101, and GSE54564) chosen from the Gene Expression Omnibus for evaluation and validation was investigated using gene characterization and functional enrichment. Then, following Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes that explore the biological processes of common genes and demonstrate the interrelationships between common genes, hub genes were obtained using the STRING database and the application cytoHubba plugin of Cytoscape software. The correlation between the gene and 22 types of immuno-infiltrating cells was explored, and the key gene as well as the diagnostic efficiency of the key gene was obtained through verification. A total of 204 shared genes were discovered, the majority of which were functionally enriched in Ribosome, Coronavirus disease COVID19, Starch and sucrose metabolism, and Galactose metabolism. Then, efforts were made to go through STRING. Immuno-infiltration studies revealed that Neutrophils, T cells CD8, T cells CD4 naive, T cells CD4 memory resting, T cells CD4 memory activated, and T cells regulatory were associated with the pathogenesis of AS and MDD. Additionally, the receiver operating characteristic curve revealed that the key gene MRPL13 played diagnostic roles in AS and MDD after intersecting 10 hub genes with 37 differential expression genes from the 2 validation datasets. The obtained results suggest an overlapping genetic structure between AS and major depression disorders. MRPL13 may provide key insights into the relationship between AS and MDD.

Project description:BACKGROUND:Major depressive disorder and bipolar disorder are prevalent and debilitating psychiatric disorders that are difficult to distinguish, as their diagnosis is based on behavioural observations and subjective symptoms. Quantitative protein profile analysis might help to objectively distinguish between these disorders and increase our understanding of their pathophysiology. Thus, this study was conducted to compare the peripheral protein profiles between the two disorders. METHODS:Serum samples were collected from 18 subjects with major depressive disorder and 15 subjects with bipolar disorder. After depleting abundant proteins, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and label-free quantification were performed. Data-dependent acquisition data were statistically analysed from the samples of 15 subjects with major depressive disorder and 10 subjects with bipolar disorder who were psychotropic drug-free. Two-sided t-tests were performed for pairwise comparisons of proteomes to detect differentially-expressed proteins (DEPs). Ingenuity Pathway Analysis of canonical pathways, disease and functions, and protein networks based on these DEPs was further conducted. RESULTS:Fourteen DEPs were significant between subjects with major depressive disorder and those with bipolar disorder. Ras-related protein Rab-7a (t = 5.975, p = 4.3 × 10- 6) and Rho-associated protein kinase 2 (t = 4.782, p = 8.0 × 10- 5) were significantly overexpressed in subjects with major depressive disorder and Exportin-7 (t = -4.520, p = 1.5 × 10- 4) was significantly overexpressed in subjects with bipolar disorder after considering multiple comparisons. Bioinformatics analysis showed that cellular functions and inflammation/immune pathways were significantly different. CONCLUSIONS:Ras-related protein Rab-7a, Rho-associated protein kinase 2, and Exportin-7 were identified as potential peripheral protein candidates to distinguish major depressive disorder and bipolar disorder. Further large sample studies with longitudinal designs and validation processes are warranted.

Dataset Information

G protein-linked signaling pathways in bipolar and major depressive disorders.

Publications

G protein-linked signaling pathways in bipolar and major depressive disorders.

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