Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università degli Studi di Napoli Federico II, Naples, Italy; CEINGE-Biotecnologie Avanzate, Naples, Italy.
J Affect Disord. 2011 Dec;135(1-3):400-4. doi: 10.1016/j.jad.2011.07.003. Epub 2011 Jul 29.
Alterations of DNA methylation and expression of suicide-related genes occurring in specific brain's areas have been associated to suicidal behavior. In the BDNF pathway, TrkB gene in frontal cortex and hippocampus, and BDNF gene in Wernicke area have been found hypermethylated and down-regulated in suicide subjects as compared to controls. In this work we investigated whether epigenetic modifications of TrkB gene occur in Wernicke area of 18 suicide subjects as compared to 18 controls.
MassArray analysis was performed to determine the methylation degree of TrkB promoter in post-mortem samples. TrkB full length and TrkB-T1 mRNA levels were assessed by quantitative RT-PCR. Geometric averaging of four internal control genes was calculated for normalization of results.
We found that TrkB and TrkB-T1 expression and promoter methylation in Wernicke area did not correlate with suicidal behavior whereas, in the same samples, the BDNF promoter IV was significantly hypermethylated in suicide with respect of controls.
Data from a single brain's area in this study's sample.
Our data show that no correlation exists between TrkB gene methylation and suicide in Wernicke area, confirming that expression and methylation state of suicide-related genes, even belonging to the same pathway, may be specific for brain area.
在特定脑区发生的 DNA 甲基化改变和与自杀相关基因的表达与自杀行为有关。在 BDNF 通路中，与对照组相比，自杀者额皮质和海马中的 TrkB 基因和韦尼克区的 BDNF 基因被发现过度甲基化和下调。在这项工作中，我们研究了 18 名自杀者和 18 名对照者韦尼克区的 TrkB 基因是否发生了表观遗传修饰。
采用 MassArray 分析方法检测死后样本中 TrkB 启动子的甲基化程度。通过定量 RT-PCR 评估 TrkB 全长和 TrkB-T1 mRNA 水平。通过计算四个内部对照基因的几何平均值来归一化结果。
我们发现，韦尼克区的 TrkB 和 TrkB-T1 表达和启动子甲基化与自杀行为无关，而在相同的样本中，BDNF 启动子 IV 在自杀者中相对于对照组明显过度甲基化。
本研究样本仅来自于单个脑区的数据。
我们的数据表明，韦尼克区 TrkB 基因甲基化与自杀之间不存在相关性，这证实了即使属于同一通路，与自杀相关基因的表达和甲基化状态也可能是特定于脑区的。
