McGill Group for Suicide Studies, McGill University, Montreal, Quebec, Canada.
Biol Psychiatry. 2011 Aug 15;70(4):312-9. doi: 10.1016/j.biopsych.2011.03.038. Epub 2011 May 14.
Suicide is an important public health problem that results from the interaction of both psychosocial and biological factors. Although it is known that particular neurobiological processes underlie suicidal ideation and behavior, there still remains limited knowledge about the specific factors involved.
To explore the neurobiology of suicide we generated microarray data from dorsal lateral prefrontal cortex (DLPFC) in each of 28 male French-Canadian subjects (20 suicide completers). These results were followed up in a larger French-Canadian sample (n = 47, 38 suicide completers) and in microarray data available from the Stanley Foundation (n = 100, 36 suicide completers). To investigate the molecular mechanisms of this finding, we performed RNA interference and electrophoretic mobility shift assays. Animal behavioral experiments were done to control for drug and alcohol effects.
We found reduced expression of Cx30 and Cx43 in DLPFC of suicide completers. We identified a previously unknown function for Sox9 as a transcription factor affecting expression of Cx30 in brain.
These results suggest that alterations of astrocyte connexins might be involved in the suicide process and provide further evidence implicating astrocytes in psychopathology.
自杀是一个重要的公共卫生问题，它是心理社会和生物因素共同作用的结果。虽然已知某些神经生物学过程是自杀意念和行为的基础，但对于涉及的具体因素仍知之甚少。
为了探索自杀的神经生物学机制，我们从 28 名加拿大男性被试者的背外侧前额叶皮层（DLPFC）中生成了微阵列数据（20 名自杀完成者）。随后在一个更大的加拿大人群样本（n = 47，38 名自杀完成者）和斯坦利基金会的微阵列数据（n = 100，36 名自杀完成者）中进行了后续研究。为了研究这一发现的分子机制，我们进行了 RNA 干扰和电泳迁移率变动分析。还进行了动物行为实验以控制药物和酒精的影响。
我们发现自杀完成者的 DLPFC 中 Cx30 和 Cx43 的表达减少。我们发现 Sox9 作为一种转录因子影响脑内 Cx30 表达具有先前未知的功能。
这些结果表明，星形胶质细胞连接蛋白的改变可能与自杀过程有关，并进一步证明星形胶质细胞在精神病理学中的作用。
