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首页> 外文期刊>The European Journal of Neuroscience >Involvement of serotonin 2C receptor RNA editing in accumbal neuropeptide Y expression and behavioural despair
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Involvement of serotonin 2C receptor RNA editing in accumbal neuropeptide Y expression and behavioural despair

机译：血清素2C受体RNA编辑参与伏隔神经肽Y表达和行为绝望

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摘要

Serotonin 2C receptors (5-HT(2C)Rs) are widely expressed in the central nervous system, and are associated with various neurological disorders. 5-HT2CR mRNA undergoes adenosine-to-inosine RNA editing at five sites within its coding sequence, resulting in expression of 24 different isoforms. Several edited isoforms show reduced activity, suggesting that RNA editing modulates serotonergic systems in the brain with causative relevance to neuropsychiatric disorders. Transgenic mice solely expressing the non-edited 5-HT2CR INI-isoform (INI) or the fully edited VGV-isoform exhibit various phenotypes including metabolic abnormalities, aggressive behaviour, anxiety-like behaviour, and depression-like behaviour. Here, we examined the behavioural phenotype and molecular changes of INI mice on a C57BL/6J background. INI mice showed an enhanced behavioural despair in the forced swimming test, elevated sensitivity to the tricyclic antidepressant desipramine, and significantly decreased serotonin in the nucleus accumbens (NAc), amygdala, and striatum. They also showed reduced expression of neuropeptide Y (NPY) mRNA in the NAc. In addition, by stereotactic injection of adeno-associated virus encoding NPY into the NAc, we demonstrated that accumbal NPY overexpression relieved behavioural despair. Our results suggest that accumbal NPY expression may be regulated by 5-HT2CR RNA editing, and its impairment may be linked to mood disorders.
机译：血清素2C受体（5-HT（2C）Rs）在中枢神经系统中广泛表达，并与各种神经系统疾病有关。 5-HT2CR mRNA在其编码序列内的五个位点进行腺苷-肌苷RNA编辑，从而表达24种不同的亚型。几种经过编辑的同工型显示出降低的活性，这表明RNA编辑可以调节脑中的血清素能系统，与神经精神疾病具有因果关系。仅表达未编辑的5-HT2CR INI同工型（INI）或完全编辑的VGV同工型的转基因小鼠表现出各种表型，包括代谢异常，攻击性行为，焦虑样行为和抑郁样行为。在这里，我们检查了C57BL / 6J背景下INI小鼠的行为表型和分子变化。 INI小鼠在强迫游泳试验中表现出增强的行为绝望感，对三环抗抑郁剂desipramine的敏感性提高，并且伏隔核（NAc），杏仁核和纹状体中的5-羟色胺明显降低。他们还显示出NAc中神经肽Y（NPY）mRNA的表达减少。此外，通过立体定向将编码NPY的腺相关病毒注射到NAc中，我们证明了NPY的过度表达可以缓解行为上的绝望。我们的结果表明，准确的NPY表达可能受5-HT2CR RNA编辑的调节，其受损可能与情绪障碍有关。

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