α 2A - and α 2C -adrenoceptor expression and functionality in postmortem prefrontal cortex of schizophrenia subjects.

Autor: Brocos-Mosquera I; Department of Pharmacology, University of the Basque Country, UPV/EHU, Leioa, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain., Gabilondo AM; Department of Pharmacology, University of the Basque Country, UPV/EHU, Leioa, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain; Biocruces Bizkaia Health Research Institute, Barakaldo, Bizkaia, Spain., Diez-Alarcia R; Department of Pharmacology, University of the Basque Country, UPV/EHU, Leioa, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain; Biocruces Bizkaia Health Research Institute, Barakaldo, Bizkaia, Spain., Muguruza C; Department of Pharmacology, University of the Basque Country, UPV/EHU, Leioa, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain., Erdozain AM; Department of Pharmacology, University of the Basque Country, UPV/EHU, Leioa, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain., Meana JJ; Department of Pharmacology, University of the Basque Country, UPV/EHU, Leioa, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain; Biocruces Bizkaia Health Research Institute, Barakaldo, Bizkaia, Spain., Callado LF; Department of Pharmacology, University of the Basque Country, UPV/EHU, Leioa, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain; Biocruces Bizkaia Health Research Institute, Barakaldo, Bizkaia, Spain. Electronic address: LF.callado@ehu.eus.
Jazyk: angličtina
Zdroj: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology [Eur Neuropsychopharmacol] 2021 Nov; Vol. 52, pp. 3-11. Date of Electronic Publication: 2021 Jun 20.
DOI: 10.1016/j.euroneuro.2021.05.012
Abstrakt: Previous evidence suggests that α 2 -adrenoceptors (α 2 -AR) may be involved in the pathophysiology of schizophrenia. However, postmortem brain studies on α 2 -AR expression and functionality in schizophrenia are scarce. The aim of our work was to evaluate α 2A -AR and α 2C -AR expression in different subcellular fractions of prefrontal cortex postmortem tissue from antipsychotic-free (absence of antipsychotics in blood at the time of death) (n = 12) and antipsychotic-treated (n = 12) subjects with schizophrenia, and matched controls (n = 24). Functional coupling of α 2 -AR to G α proteins induced by the agonist UK14304 was also tested. Additionally, G α protein expression was also evaluated. In antipsychotic-free schizophrenia subjects, α 2A -AR and α 2C -AR protein expression was similar to controls in all the subcellular fractions. Conversely, in antipsychotic-treated schizophrenia subjects, increased α 2A -AR expression was found in synaptosomal plasma membrane and postsynaptic density (PSD) fractions (+60% and +79% vs controls, respectively) with no significant changes in α 2C -AR. [ 35 S]GTPγS SPA experiments showed a significant lower stimulation of G αi2 and G αi3 proteins by UK14304 in antipsychotic-treated schizophrenia subjects, whereas stimulation in antipsychotic-free schizophrenia subjects remained unchanged. G αo protein stimulation was significantly decreased in both antipsychotic-free and antipsychotic-treated schizophrenia subjects compared to controls. Expression of G αi3 protein did not differ between groups, whereas G αi2 levels were increased in PSD of schizophrenia subjects, both antipsychotic-free and antipsychotic-treated. G αo protein expression was increased in PSD of antipsychotic-treated subjects and in the presynaptic fraction of antipsychotic-free schizophrenia subjects. The present results suggest that antipsychotic treatment is able to modify in opposite directions both the protein expression and the functionality of α 2A -AR in the cortex of schizophrenia patients.
(Copyright © 2021. Published by Elsevier B.V.)
Databáze: MEDLINE
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