Regulator of G-protein signalling (RGS) proteins inhibit signalling by G-protein-coupled receptors (GPCRs). GPCRs mediate the functions of several important neurotransmitters and serve as targets of many anti-psychotics. RGS2, RGS4, RGS5 and RGS16 are located on chromosome 1q23.3–31, a locus found to be associated with schizophrenia. Although previous gene expression analysis detected down-regulation of RGS4 expression in brain samples of patients with schizophrenia, the results were not consistent. In the present study, we performed a systematic meta-analysis of differential RGS2, RGS4, RGS5 and RGS16 expression in Brodmann Area 10 (BA10) samples of patients with schizophrenia and from healthy controls. Two microarray datasets met the inclusion criteria (overall, 41 schizophrenia samples and 38 controls were analysed). RGS2 and RGS16 were found to be up-regulated in BA10 samples of individuals with schizophrenia, whereas no differential expression of RGS4 and RGS5 was detected. Analysis of dorso-lateral prefrontal cortex samples of the CommonMind Consortium (258 schizophrenia samples vs. 279 controls) further validated the results. Given their central role in inactivating G-protein-coupled signalling pathways, our results suggest that differential gene expression might lead to enhanced inactivation of G-protein signalling in schizophrenia. This, in turn, suggests that additional studies are needed to further explore the consequences of the differential expression we detected, this time at the protein and functional levels.
|Number of pages||13|
|Journal||European Journal of Neuroscience|
|Early online date||28 Nov 2022|
|State||Published - Jan 2023|
Bibliographical noteFunding Information:
We thank Professor Eytan Domany for his help with the infrastructure that enabled the performance of this project. The CMC data were generated as part of the CMC supported by funding from Takeda Pharmaceuticals, F. Hoffman‐La Roche and NIH grants R01MH085542, R01MH093725, P50MH066392, P50MH080405, R01MH097276, RO1‐MH‐075916, P50M096891, P50MH084053S1, R37MH057881, R37MH057881S1, HHSN271201300031C, AG02219, AG05138 and MH06692. Brain tissue for the study was obtained from the Mount Sinai NIH Brain and Tissue Repository, the University of Pennsylvania Alzheimer's Disease Core Center, the University of Pittsburgh NeuroBioBank and Brain and Tissue Repositories and the NIMH Human Brain Collection Core. CMC Leadership: Pamela Sklar, Joseph Buxbaum (Icahn School of Medicine at Mount Sinai), Bernie Devlin, David Lewis (University of Pittsburgh), Raquel Gur, Chang‐Gyu Hahn (University of Pennsylvania), Keisuke Hirai, Hiroyoshi Toyoshiba (Takeda Pharmaceuticals), Enrico Domenici, Laurent Essioux (F. Hoffman‐La Roche), Lara Mangravite, Mette Peters (Sage Bionetworks), Thomas Lehner, Barbara Lipska (NIMH).
© 2022 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
- Brodmann Area 10
- gene expression
- regulator of G-protein signalling (RGS)
ASJC Scopus subject areas
- Neuroscience (all)