Monsalve Eva M, García-Gutiérrez María S, Navarrete Francisco, Giner Salvador, Laborda Jorge, Manzanares Jorge
Facultad de Medicina, Universidad de Castilla-La Mancha/Centro Regional de Investigaciones Biomédicas (CRIB), Albacete, Spain.
Mol Neurobiol. 2014 Apr;49(2):957-65. doi: 10.1007/s12035-013-8570-z. Epub 2013 Oct 23.
Recent studies have associated alterations of neuronal plasticity in specific brain areas with suicidal behavior. The Notch signaling pathway plays a relevant role in the control of stem cell maintenance, cell migration, and neuronal plasticity. In the present study, the gene expression of the four Notch receptors (NOTCH1-4), the five canonical ligands (DLL1, DLL3, DLL4, JAGGED1, and JAGGED2), the two non-canonical ligands (DLK1 and DLK2), and the transcription factors (HES1, HEY1, and HEY2) were measured in the dorsolateral prefrontal cortex (DLPFC) and amygdala (AMY) of suicide victims (S; n = 13 males, with no clinical psychiatric history and non-treated with anxiolytic or antidepressant drugs) and their corresponding controls (C; n = 13 males) by real-time PCR. The results revealed a reduction of NOTCH2 and NOTCH1, NOTCH3, and NOTCH4 gene expression in the DLPFC and AMY of S compared with C, respectively. DLL1 levels were increased in the DLPFC and decreased in the AMY, whereas DLL4, JAGGED1, and JAGGED2 were significantly decreased in the regions analyzed. DLK1 was reduced in the AMY, whereas no changes were observed in the DLPFC and in DLK2 expression levels in any of the regions analyzed. HES1 was significantly reduced in both brain regions from S, whereas there were no significant changes in HEY1 and HEY2. This study provides evidence suggesting that the Notch signaling pathway could be a potential key target in the treatment of suicidal behaviors.
近期研究已将特定脑区神经元可塑性的改变与自杀行为联系起来。Notch信号通路在干细胞维持、细胞迁移和神经元可塑性的控制中发挥着相关作用。在本研究中，通过实时PCR检测了自杀受害者（S组；n = 13名男性，无临床精神病史且未接受抗焦虑或抗抑郁药物治疗）及其相应对照（C组；n = 13名男性）的背外侧前额叶皮质（DLPFC）和杏仁核（AMY）中四种Notch受体（NOTCH1 - 4）、五种经典配体（DLL1、DLL3、DLL4、JAGGED1和JAGGED2）、两种非经典配体（DLK1和DLK2）以及转录因子（HES1、HEY1和HEY2）的基因表达。结果显示，与C组相比，S组DLPFC和AMY中NOTCH2以及NOTCH1、NOTCH3和NOTCH4的基因表达分别降低。DLL1水平在DLPFC中升高而在AMY中降低，而DLL4、JAGGED1和JAGGED2在分析区域中显著降低。DLK1在AMY中降低，而在DLPFC中未观察到变化，且在任何分析区域中DLK2表达水平均无变化。S组两个脑区中的HES1均显著降低，而HEY1和HEY2无显著变化。本研究提供的证据表明，Notch信号通路可能是治疗自杀行为的一个潜在关键靶点。
