Title |
Region-specific alterations of A-to-I RNA editing of serotonin 2c receptor in the cortex of suicides with major depression
|
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Published in |
Translational Psychiatry, August 2016
|
DOI | 10.1038/tp.2016.121 |
Pubmed ID | |
Authors |
D Weissmann, S van der Laan, M D Underwood, N Salvetat, L Cavarec, L Vincent, F Molina, J J Mann, V Arango, J F Pujol |
Abstract |
Brain region-specific abnormalities in serotonergic transmission appear to underlie suicidal behavior. Alterations of RNA editing on the serotonin receptor 2C (HTR2C) pre-mRNA in the brain of suicides produce transcripts that attenuate 5-HT2CR signaling by impairing intracellular G-protein coupling and subsequent intracellular signal transduction. In brain, the distribution of RNA-editing enzymes catalyzing deamination (A-to-I modification) shows regional variation, including within the cerebral cortex. We tested the hypothesis that altered pre-mRNA 5-HT2CR receptor editing in suicide is region-specific. To this end, we investigated the complete 5-HT2CR mRNA-editing profile in two architectonically distinct cortical areas involved in mood regulation and decision-making in a clinically well-characterized cohort of age- and sex-matched non-psychiatric drug-free controls and depressed suicides. By using an original biochemical detection method, that is, capillary electrophoresis single-stranded conformational polymorphism (CE-SSCP), we corroborated the 5-HT2CR mRNA-editing profile previously described in the dorsolateral prefrontal cortex (Brodmann area 9 (BA9)). Editing of 5-HT2CR mRNA displayed clear regional difference when comparing dorsolateral prefrontal cortex (BA9) and anterior cingulate cortex (BA24). Compared with non-psychiatric control individuals, alterations of editing levels of 5-HT2CR mRNA were detected in both cortical areas of depressed suicides. A marked increase in editing on 5-HT2CR was especially observed in the anterior cingulate cortex in suicides, implicating this cortical area in suicide risk. The results suggest that region-specific changes in RNA editing of 5-HT2CR mRNA and deficient receptor function likely contribute to the etiology of major depressive disorder or suicide. |
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Geographical breakdown
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Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 11 | 14% |
Researcher | 9 | 12% |
Student > Master | 6 | 8% |
Student > Doctoral Student | 5 | 6% |
Other | 11 | 14% |
Unknown | 24 | 31% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 6 | 8% |
Other | 13 | 17% |
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