Dataset Information

??-Adrenoceptor functionality in postmortem frontal cortex of depressed suicide victims.

ABSTRACT: Alterations in brain density and signaling associated with monoamine receptors are believed to play a role in depressive disorders. This study evaluates the functional status of ??(A)-adrenoceptors in postmortem frontal cortex of depressed subjects.G-protein activation and inhibition of adenylyl cyclase (AC) activity induced by the ??-adrenoceptor agonist UK14304 were measured in triplicate in samples from 15 suicide victims with an antemortem diagnosis of major depression and 15 matched control subjects.Basal [³?S] guanosine ? thio-phosphate (GTP?S) binding and cyclic adenosine monophosphate accumulation did not differ between groups. In depressed victims, an increase in [³?S] GTP?S binding potency (EC?? = .58 ?mol/L vs. EC?? = 3.31 ?mol/L; p < .01; depressed vs. control) and a significant reduction in the maximal inhibition of AC activity (I(max) = 27 ± 4% vs. I(max) = 47 ± 5%; p < .01) were observed after incubation with the ?(2)-adrenoceptor agonist UK14304. No differences were found between antidepressant-free and antidepressant-treated subjects. A significant relationship between EC?? values for [³?S] GTP?S and I(max) values for AC assay was found (n = 30; r = -.43; p < .05).The dual regulation of ?(2A)-adrenoceptor signaling pathways raises the possibility that factors affecting the G-protein cycle and/or selective access of G?(i/o)-protein to AC might be relevant to receptor abnormalities in depression, providing further support for the involvement of ??(A)-adrenoceptors in the pathogenesis of depression.

SUBMITTER: Valdizan EM

PROVIDER: S-EPMC3562997 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

α₂-Adrenoceptor functionality in postmortem frontal cortex of depressed suicide victims.

Valdizán Elsa M EM Díez-Alarcia Rebeca R González-Maeso Javier J Pilar-Cuéllar Fuencisla F García-Sevilla Jesús A JA Meana J Javier JJ Pazos Angel A

Biological psychiatry 20100922 9

<h4>Background</h4>Alterations in brain density and signaling associated with monoamine receptors are believed to play a role in depressive disorders. This study evaluates the functional status of α₂(A)-adrenoceptors in postmortem frontal cortex of depressed subjects.<h4>Methods</h4>G-protein activation and inhibition of adenylyl cyclase (AC) activity induced by the α₂-adrenoceptor agonist UK14304 were measured in triplicate in samples from 15 suicide victims with an antemortem diagnosis of majo ...[more]

PMID: 20864091

Similar Datasets

Project description:Background: TrkB-T1 is a BDNF receptor lacking a tyrosine kinase domain that is highly expressed in astrocytes and regulates BDNF-evoked calcium transients. Previous studies indicate that downregulation of TrkB-T1 in frontal cortex may be involved in neurobiological processes underlying suicide. Methods: In a microarray screening study (N=8), we interrogated all known microRNA in the frontal cortex of suicide completers with low expression of TrkB-T1 and normal controls. These findings were validated and followed up in a larger sample of cases and controls (N=55) Functional analyses included microRNA silencing, microRNA overexpression and luciferase assays to investigate specificity and to validate interactions between differentially expressed microRNA and TrkB-T1 Results: microRNAs Hsa-miR-185* and Hsa-miR-491-3p were upregulated in suicide completers with low expression of TrkB.T1 (Pnominal: 9.10-5 and 1.8.10-4 respectively; FDR-corrected p=0.031). Bioinformatic analyses revealed five putative binding sites for the DiGeorge syndrome linked microRNA Hsa-miR-185*in the 3M-bM-^@M-^YUTR of TrkB-T1, but none for Hsa-miR-491-3P. The increase of Hsa-miR-185* in frontal cortex of suicide completers was validated then confirmed in a larger, randomly selected group of suicide completers, where an inverse correlation between Hsa-miR-185* and TrkB-T1 expression was observed ( R=-0.404; p=0.002). Silencing and overexpression studies performed in human cell lines confirmed the inverse relationship between hsa-mir-185* and trkB-T1 expression. Luciferase assays demonstrated that Hsa-miR-185* binds to sequences in the 3M-bM-^@M-^YUTR of TrkB-T1. Conclusion: These results suggest that an increase of Hsa-miR-185* expression levels regulates, at least in part, the TrkB-T1 decrease observed in the frontal cortex of suicide completers and further implicate the 3MB 22q11 region in psychopathology. The microarray analysis consists in to compare the microRNA profile of four suicide completers with low TrkB-T1 expression level and four controls. Each RNA extract was labeled with Hy3 and hybridyzed with a reference sample labeled with Hy5. The reference sample was a pool of the eight RNA samples

Dataset Information

??-Adrenoceptor functionality in postmortem frontal cortex of depressed suicide victims.

Publications

α₂-Adrenoceptor functionality in postmortem frontal cortex of depressed suicide victims.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets