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

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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.

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Acknowledgments

This study was supported by grants from MINECO-FEDER (SAF2009-08460), Basque Government (IT-199/07), and UPV/EHU to J.J.M., and from SAF2011-29918 to J.A.G.S. G.R. was supported by a fellowship from the Basque Government. The authors wish to thank the staff members of the Basque Institute of Legal Medicine, Bilbao, and the Romand University Center of Legal Medicine, Geneva, for their cooperation in the study and Dr. Javier Ballesteros from the Department of Neurosciences, University of the Basque Country UPV/EHU for the useful statistical assistance.

Conflicts of interest

The authors declare no conflict of interest.

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Author notes

  1. G. Rivero

    Present address: Omnia Molecular Ltd., Barcelona Science Park, 08028, Barcelona, Spain

Authors and Affiliations

  1. Department of Pharmacology, BioCruces Health Research Institute, University of the Basque Country UPV/EHU and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), 48940, Leioa, Bizkaia, Spain

    G. Rivero, A. M. Gabilondo, L. F. Callado & J. J. Meana

  2. Laboratory of Neuropharmacology, IUNICS and Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), University of the Balearic Islands, 07122, Palma de Mallorca, Spain

    J. A. García-Sevilla

  3. Centre Universitaire Romand de Médecine Légale-Site Genève, Faculté de Médecine, Université de Genève, 1211, Genève 4, Switzerland

    R. La Harpe

  4. Basque Institute of Legal Medicine, 48001, Bilbao, Spain

    B. Morentin

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Rivero, G., Gabilondo, A.M., García-Sevilla, J.A. et al. Brain RGS4 and RGS10 protein expression in schizophrenia and depression. Effect of drug treatment. Psychopharmacology 226, 177–188 (2013). https://doi.org/10.1007/s00213-012-2888-5

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