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PMID: 21784156 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural

Reduced expression of G protein-coupled receptor kinases in schizophrenia but not in schizoaffective disorder.

Neurobiology of disease ·Vol. 44 ·No. 2 ·2011-11-00 ·Pages 248-58

Bychkov ER, Ahmed MR, Gurevich VV, Benovic JL, Gurevich EV

Abstract

Alterations of multiple G protein-mediated signaling pathways are detected in schizophrenia. G protein-coupled receptor kinases (GRKs) and arrestins terminate signaling by G protein-coupled receptors exerting a powerful influence on receptor functions. Modifications of arrestin and/or GRKs expression may contribute to schizophrenia pathology. Cortical expression of arrestins and GRKs was measured postmortem in control and subjects with schizophrenia or schizoaffective disorder. Additionally, arrestin/GRK expression was determined in elderly patients with schizophrenia and age-matched control. Patients with schizophrenia, but not schizoaffective disorder, displayed a reduced concentration of arrestin and GRK mRNAs and GRK3 protein. Arrestins and GRK significantly decreased with age. In elderly patients, GRK6 was reduced, with other GRKs and arrestins unchanged. A reduced cortical concentration of GRKs in schizophrenia (resembling that in aging) may result in altered G protein-dependent signaling, thus contributing to prefrontal deficits in schizophrenia. The data suggest distinct molecular mechanisms underlying schizophrenia and schizoaffective disorder.

MeSH Terms
Adult Aged Aged, 80 and over Arrestins/biosynthesis,deficiency,genetics Cohort Studies Female G-Protein-Coupled Receptor Kinase 2/biosynthesis,deficiency,genetics G-Protein-Coupled Receptor Kinase 3/biosynthesis,deficiency,genetics G-Protein-Coupled Receptor Kinase 5/biosynthesis,deficiency,genetics G-Protein-Coupled Receptor Kinases/biosynthesis,deficiency,genetics Humans Male Middle Aged Prefrontal Cortex/metabolism,physiopathology Psychotic Disorders/genetics,metabolism,physiopathology Schizophrenia/genetics,metabolism,physiopathology Young Adult
Chemicals
Arrestins G-Protein-Coupled Receptor Kinase 3 GRK2 protein, human GRK3 protein, human G-Protein-Coupled Receptor Kinase 2 G-Protein-Coupled Receptor Kinase 5 G-Protein-Coupled Receptor Kinases G-protein-coupled receptor kinase 6 GRK5 protein, human
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Bychkov E R
Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
Ahmed M R
Gurevich V V
Benovic J L
Gurevich E V
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Article Info
Journal
Neurobiology of disease
Abbr.
Neurobiol Dis
ISSN
1095-953X
DOI
10.1016/j.nbd.2011.07.009
Published
2011-11-00
Epub
2011-00-20
Pages
248-58
Language
English
Region
United States
NLM ID
9500169
PMCID
PMC3166984
Subset
IM
Grants
NINDS NIH HHS · R01 NS045117-01A1 · United States
NIGMS NIH HHS · GM47417 · United States
NIGMS NIH HHS · R01 GM077561 · United States
NINDS NIH HHS · NS065868 · United States
NINDS NIH HHS · NS045117 · United States
NINDS NIH HHS · R01 NS045117 · United States
NIGMS NIH HHS · R01 GM047417 · United States
NINDS NIH HHS · R01 NS065868-01 · United States
NIMH NIH HHS · MH068855 · United States
NIMH NIH HHS · MH066392 · United States
NIGMS NIH HHS · GM77561 · United States
NINDS NIH HHS · R01 NS065868 · United States
NIMH NIH HHS · P50 MH066392 · United States
NIMH NIH HHS · R24 MH068855 · United States
NIGMS NIH HHS · R37 GM047417 · United States
External Links
PubMed source DOI: 10.1016/j.nbd.2011.07.009 PMC Full Text View journal details
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