Serotonin 2C receptors: Suicide, serotonin, and runaway RNA editing

被引:47
作者
Schmauss, C
机构
[1] Columbia Univ Coll Phys & Surg, Dept Psychiat & Neurosci, New York, NY 10032 USA
[2] New York State Psychiat Inst & Hosp, New York, NY 10032 USA
关键词
serotonin; RNA editing; serotonin 2C receptor; prefrontal cortex; major depression; schizophrenia;
D O I
10.1177/1073858403253669
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Transcripts of the gene encoding the serotonin 2C receptor are modified by RNA editing, a posttranscriptional process that converts adenosines to inosines. This editing changes up to three genomically encoded amino acids located in the second intracellular loop of the G-protein-coupled receptor. Compared with nonedited receptors, extensively edited receptor isoforms activate G protein less efficiently. Studies on mice revealed that 5-HT2C pre-mRNA editing is regulated in a serotonin-dependent manner, and postmortem studies on brain tissues of patients with schizophrenia and major depression found distinct site-specific alterations of this editing in the prefrontal cortex, a brain region expressing a large number of differently edited 5-HT2C mRNA isoforms. At present, the most complex alterations in 5-HT2C pre-mRNA editing were found in brains of depressed suicide victims. In these brains, 5-HT2C receptor isoforms with reduced function are expressed at significantly increased levels, suggesting that the regulation of editing by synaptic serotonin is defective.
引用
收藏
页码:237 / 242
页数:6
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