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Increased G protein-coupled receptor kinase (GRK) expression in the anterior cingulate cortex in schizophrenia.
- Source :
-
Schizophrenia research [Schizophr Res] 2014 Oct; Vol. 159 (1), pp. 130-5. Date of Electronic Publication: 2014 Aug 19. - Publication Year :
- 2014
-
Abstract
- Background: Current pharmacological treatments for schizophrenia target G protein-coupled receptors (GPCRs), including dopamine receptors. Ligand-bound GPCRs are regulated by a family of G protein-coupled receptor kinases (GRKs), members of which uncouple the receptor from heterotrimeric G proteins, desensitize the receptor, and induce receptor internalization via the arrestin family of scaffolding and signaling molecules. GRKs initiate the activation of downstream signaling pathways, can regulate receptors and signaling molecules independent of GPCR phosphorylation, and modulate epigenetic regulators like histone deacetylases (HDACs). We hypothesize that the expression of GRK proteins is altered in schizophrenia, consistent with previous findings of alterations upstream and downstream from this family of molecules that facilitate intracellular signaling processes.<br />Methods: In this study, we measured protein expression via Western blot analysis for GRKs 2, 3, 5, and 6 in the anterior cingulate cortex of patients with schizophrenia (n=36) and a comparison group (n=33). To control for antipsychotic treatment, we measured these same targets in haloperidol-treated vs. untreated rats (n=10 for both).<br />Results: We found increased levels of GRK5 in schizophrenia. No changes were detected in GRK protein expression in rats treated with haloperidol decanoate for 9 months.<br />Conclusion: These data suggest that increased GRK5 expression may contribute to the pathophysiology of schizophrenia via abnormal regulation of the cytoskeleton, endocytosis, signaling, GPCRs, and histone modification.<br /> (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Subjects :
- Aged
Aged, 80 and over
Analysis of Variance
Animals
Antipsychotic Agents pharmacology
Female
Gene Expression Regulation drug effects
Gyrus Cinguli drug effects
Haloperidol pharmacology
Humans
Male
Middle Aged
Rats
Rats, Sprague-Dawley
Signal Transduction physiology
G-Protein-Coupled Receptor Kinases metabolism
Gene Expression Regulation physiology
Gyrus Cinguli metabolism
Schizophrenia pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1573-2509
- Volume :
- 159
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Schizophrenia research
- Publication Type :
- Academic Journal
- Accession number :
- 25153362
- Full Text :
- https://doi.org/10.1016/j.schres.2014.07.040