Brain RGS4 and RGS10 Protein Expression in Schizophrenia and Depression. Effect of Drug Treatment

Psychopharmacology (Berl). 2013 Mar;226(1):177-88. doi: 10.1007/s00213-012-2888-5. Epub 2012 Oct 24.

Abstract

Rationale: Regulator of G-protein signaling (RGS) proteins, RGS4 and RGS10, may be involved in the pathophysiology of schizophrenia. RGS4 has attracted special interest since the reports of genetic association between SNPs in RGS4 and schizophrenia. However, there is no information about the subcellular distribution of RGS4 and RGS10 proteins in psychiatric disorders.

Objectives: Plasma membrane RGS4 and cytosolic RGS10 protein immunoreactivity in prefrontal cortex from schizophrenic subjects (n = 25), non-diagnosed suicides (n = 13), and control subjects (n = 35), matched by age, gender, and postmortem delay, was analyzed by western blot. A second group of depressed subjects (n = 25) and control subjects (n = 25) was evaluated. The effect of the antipsychotic or antidepressant treatments was also assessed.

Results: No significant differences in plasma membrane RGS4 and cytosolic RGS10 protein expression were observed between schizophrenic subjects, non-diagnosed suicides, and control subjects. However, RGS4 immunoreactivity was significantly higher (Δ = 33 ± 10 %, p < 0.05) in the antipsychotic-treated subgroup (n = 12) than in the antipsychotic-free subgroup (n = 13). Immunodensities of plasma membrane RGS4 and cytosolic RGS10 proteins did not differ between depressed and matched control subjects.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / blood
  • Antipsychotic Agents / therapeutic use*
  • Biopsy
  • Blotting, Western
  • Cell Membrane / metabolism
  • Cytosol / metabolism
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / metabolism*
  • Depressive Disorder, Major / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Postmortem Changes
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / pathology
  • RGS Proteins / biosynthesis*
  • Schizophrenia / drug therapy
  • Schizophrenia / metabolism*
  • Schizophrenia / pathology
  • Suicide

Substances

  • Antipsychotic Agents
  • RGS Proteins
  • RGS10 protein, human
  • RGS4 protein