Dataset Information

Serotonin 2c receptor RNA editing in major depression and suicide.

ABSTRACT: mRNA for serotonin 2C receptor (5-HT(2C)R) undergoes editing which results in numerous isoforms. More highly edited isoforms exhibit decreased function. We recently found greater 5-HT(2C)R editing in suicide victims with prior bipolar disorder (BPD) or schizophrenia (SZ) compared with non-suicide patients and normal controls (NC). This study compares suicides and non-suicides with major depressive disorder (MDD(Suic) and MDD(NoSuic)) and non-suicide NC.mRNA editing was assessed in prefrontal cortex of 24 MDD(Suic), 21 MDD(NoSuic), and 56 NC using next generation sequencing. mRNA expression of 5-HT(2C)R and editing enzymes (ADAR1-2) was assessed by real-time PCR.Editing was lower in MDD(NoSuic) than in MDD(Suic), which did not differ from NC. No differences in the 5-HT(2C)R or ADAR1 expression were detected. ADAR2 expression was higher in NC than in MDD subjects, but did not differ between MDD(NoSuic) and MDD(Suic).Our findings suggest the presence of two factors associated with 5-HT(2C)R editing. One factor, which probably stems from decreased ADAR2 expression, is linked to MDD and is associated with less editing. The other, seen also in our previous study of suicide in BP and SZ, is linked to suicide alone and is associated with more editing and, therefore, less receptor function.

SUBMITTER: Lyddon R

PROVIDER: S-EPMC4120662 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Serotonin 2c receptor RNA editing in major depression and suicide.

Lyddon Rebecca R Dwork Andrew J AJ Keddache Mehdi M Siever Larry J LJ Dracheva Stella S

The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry 20120309 8

<h4>Objectives</h4>mRNA for serotonin 2C receptor (5-HT(2C)R) undergoes editing which results in numerous isoforms. More highly edited isoforms exhibit decreased function. We recently found greater 5-HT(2C)R editing in suicide victims with prior bipolar disorder (BPD) or schizophrenia (SZ) compared with non-suicide patients and normal controls (NC). This study compares suicides and non-suicides with major depressive disorder (MDD(Suic) and MDD(NoSuic)) and non-suicide NC.<h4>Methods</h4>mRNA edi ...[more]

PMID: 22404657

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Project description:Type 2 diabetes mellitus (T2DM) describes a group of metabolic disorders characterized by defects in insulin secretion and insulin sensitivity. Insulin secretion from pancreatic β-cells is an important factor in the etiology of T2DM, though the complex regulation and mechanisms of insulin secretion from β-cells remains to be fully elucidated. High plasma levels of serotonin (5-hydroxytryptamine; 5-HT) have been reported in T2DM patients, though the potential effect on insulin secretion is unclear. However, it is known that the 5-HT receptor 2C (5-HT(2C)R) agonist, mCPP, decreases plasma insulin concentration in mice. As such, we aimed to investigate the expression of the 5-HT(2C)R in pancreatic islets of diabetic mice and the role of 5-HT(2C)R signaling in insulin secretion from pancreatic β-cells. We found that 5-HT(2C)R expression was significantly increased in pancreatic islets of db/db mice. Furthermore, treatment with a 5-HT(2C)R antagonist (SB242084) increased insulin secretion from pancreatic islets isolated from db/db mice in a dose-dependent manner, but had no effect in islets from control mice. The effect of a 5-HT(2C)R agonist (mCPP) and antagonist (SB242084) were further studied in isolated pancreatic islets from mice and Min-6 cells. We found that mCPP significantly inhibited insulin secretion in Min-6 cells and isolated islets in a dose-dependent manner, which could be reversed by SB242084 or RNA interference against 5-HT(2C)R. We also treated Min-6 cells with palmitic acid for 24 h, and found that the expression of 5-HT(2C)R increased in a dose-dependent manner; furthermore, the inhibition of insulin secretion in Min-6 cells induced by palmitic acid could be reversed by SB242084 or RNA interference against 5-HT(2C)R. Taken together, our data suggests that increased expression of 5-HT(2C)R in pancreatic β-cells might inhibit insulin secretion. This unique observation increases our understanding of T2DM and suggests new avenues for potential treatment.

Dataset Information

Serotonin 2c receptor RNA editing in major depression and suicide.

Publications

Serotonin 2c receptor RNA editing in major depression and suicide.

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