Brain RGS4 and RGS10 protein expression in schizophrenia and depression. Effect of drug treatment

Abstract

Expression of RGS4 and RGS10 proteins at their predominant subcellular location was studied in the postmortem brain of subjects with psychiatric disorders. The results suggest unaltered membrane RGS4 and cytosolic RGS10 proteins levels in schizophrenia and major depression. Antipsychotic treatment seems to increase membrane RGS4 immunoreactivity. Further studies are needed to elucidate RGS4 and RGS10 functional status.

Regulators of G-Protein-Signaling Proteins: Negative Modulators of G-Protein-Coupled Receptor Signaling

“…A significant amount of research has been devoted to looking at the role of RGS4 as a potential etiological factor for schizophrenia (Bani-Fatemi et al, 2013;Cheng et al, 2013;Gong et al, 2013;Lener et al, 2013;Monroy et al, 2013a;Rivero et al, 2013;Rose and Donohoe, 2013;Schwendt et al, 2012;Steiner et al, 2014). Postmortem studies showed lowered levels of RGS4 expression in many locations in the frontal cortex of schizophrenics, such as the superior temporal gyrus (Bowden et al, 2007).…”

Reciprocal Alterations in Regulator of G Protein Signaling 4 and microRNA16 in Schizophrenia

“…For example, some protein studies of RGS4 protein used antibodies that detect a band of higher molecular weight than is predicted for RGS4. 14,15 Subject characteristics that reflect both protein and mRNA quality were not reported, differed between diagnostic groups, or had values suggesting that the preservation of mRNA or protein was less than ideal in some previous studies.…”

“…26 Although the present and previous 10-12 studies have found lower RGS4 mRNA and protein expression in the DLPFC of schizophrenia, other studies have found no differences between healthy comparison and schizophrenia subjects in the DLPFC. [13][14][15] Methodological and subject characteristics may contribute to these disparate findings. For example, some protein studies of RGS4 protein used antibodies that detect a band of higher molecular weight than is predicted for RGS4.…”

“…[13][14][15] These apparent discrepancies could reflect differences in cohort characteristics or quantification methods across studies. In addition, since RGS4 exhibits prominent laminar and cellular patterns of expression in primate DLPFC, 16 such that most labeled neurons are pyramidal cells in layers 2, 3, and 5, cellular level analyses might have greater sensitivity for the detection of a disease effect on RGS4 levels.…”

Physiology of RGS10 in Neurons and Immune Cells

“…However, immunohistochemical analysis of RGS10 protein in postmortem human brain tissue revealed that the levels of RGS10 in schizophrenia and major depression were comparable to that of healthy control subjects. 64,65 Interestingly, RGS proteins do negatively regulate G αi/o protein activity as well as μ-opioid receptor (MORs) function. In support of this possibility, the levels of RGS10 in frontal cortex of short-term opiate abusers are significantly decreased but remain relatively similar to control levels in longterm opiate abusers, 66 suggesting RGS10 may play a role in opiate tolerance, dependence, and/or withdrawal.…”