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自杀者前额皮质中核糖体 DNA 转录减少:新的分子 RT-qPCR 研究结果与先前经 AgNOR 染色的锥形神经元形态计量数据一致。

Reduced ribosomal DNA transcription in the prefrontal cortex of suicide victims: consistence of new molecular RT-qPCR findings with previous morphometric data from AgNOR-stained pyramidal neurons.

机构信息

Department of Forensic Medicine, Medical University of Gdańsk, ul. Dębowa 23, 80-204, Gdańsk, Poland.

Department of Psychiatry, Otto von Guericke University, Magdeburg, Germany.

出版信息

Eur Arch Psychiatry Clin Neurosci. 2021 Apr;271(3):567-576. doi: 10.1007/s00406-021-01232-4. Epub 2021 Jan 26.

Abstract

Prefrontal cortical regions play a key role in behavioural regulation, which is profoundly disturbed in suicide. The study was carried out on frozen cortical samples from the anterior cingulate cortex (dorsal and ventral parts, ACd and ACv), the orbitofrontal cortex (OFC), and the dorsolateral cortex (DLC) obtained from 20 suicide completers (predominantly violent) with unknown psychiatric diagnosis and 21 non-suicidal controls. The relative level of ribosomal RNA (rRNA) as a marker of the transcriptional activity of ribosomal DNA (rDNA) was evaluated bilaterally in prefrontal regions mentioned above (i.e. in eight regions of interest, ROIs) by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). The overall statistical analysis revealed a decrease in rDNA activity in suicide victims versus controls, particularly in male subjects. Further ROI-specific post hoc analyses revealed a significant decrease in this activity in suicides compared to non-suicides in five ROIs. This effect was accentuated in the ACv, where it was observed bilaterally. Our findings suggest that decreased rDNA transcription in the prefrontal cortex plays an important role in suicide pathogenesis and corresponds with our previous morphometric analyses of AgNOR-stained neurons.

摘要

前额皮质区域在行为调节中发挥着关键作用,而自杀行为则会严重扰乱这种调节。本研究对 20 名自杀既遂者(主要为暴力自杀者)和 21 名非自杀对照者的冰冻皮质样本进行了研究,这些样本取自前扣带皮质(背侧和腹侧部分,ACd 和 ACv)、眶额皮质(OFC)和背外侧皮质(DLC)。通过逆转录和定量聚合酶链反应(RT-qPCR),评估了上述前额皮质区域(即 8 个感兴趣区域,ROI)中核糖体 RNA(rRNA)作为核糖体 DNA(rDNA)转录活性的标志物的相对水平。总的统计分析显示,与对照组相比,自杀者的 rDNA 活性降低,尤其是男性。进一步的 ROI 特异性事后分析显示,在 5 个 ROI 中,与非自杀者相比,自杀者的这种活性显著降低。这种效应在 ACv 中更为明显,并且在双侧都观察到了这种效应。我们的研究结果表明,前额皮质中 rDNA 转录的减少在自杀发病机制中起着重要作用,这与我们之前对 AgNOR 染色神经元的形态计量学分析结果相符。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fed8/7981327/235c3dbb86a3/406_2021_1232_Fig1_HTML.jpg

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