Dwivedi Yogesh, Rizavi Hooriyah S, Conley Robert R, Roberts Rosalinda C, Tamminga Carol A, Pandey Ghanshyam N
Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 60612, USA.
Arch Gen Psychiatry. 2003 Aug;60(8):804-15. doi: 10.1001/archpsyc.60.8.804.
Suicide is a major public health concern. Although authors of many studies have examined the neurobiological aspects of suicide, the molecular mechanisms associated with suicidal behavior remain unclear. Brain-derived neurotrophic factor (BDNF), one of the most important neurotrophins, after binding with and activating receptor tyrosine kinase B (trk B), is directly involved in many physiological functions in the brain, including cell survival and synaptic plasticity. The present study was performed to examine whether the expression of BDNF and/or trk B isoforms was altered in postmortem brain in subjects who commit suicide (hereafter referred to as suicide subjects) and whether these alterations were associated with specific psychopathologic conditions.
These studies were performed in prefrontal cortex in Brodmann area 9 and hippocampus obtained in 27 suicide subjects and 21 nonpsychiatric control subjects. Levels of messenger RNA and protein levels of BDNF and trk B were determined with competitive reverse transcriptase-polymerase chain reaction and Western blot technique, respectively. The level of neuron-specific enolase messenger RNA as a neuronal marker was also determined in these brain areas.
Messenger RNA levels of BDNF and trk B were significantly reduced, independently and as a ratio to neuron-specific enolase, in both prefrontal cortex and hippocampus in suicide subjects, as compared with those in control subjects. These reductions were associated with significant decreases in the protein levels of BDNF and of full-length trk B but not trk B's truncated isoform. These changes were present in all suicide subjects regardless of psychiatric diagnosis and were unrelated to postmortem interval, age, sex, or pH of the brain.
Given the importance of BDNF in mediating physiological functions, including cell survival and synaptic plasticity, our findings of reduced expression of BDNF and trk B in postmortem brain in suicide subjects suggest that these molecules may play an important role in the pathophysiological aspects of suicidal behavior.
自杀是一个重大的公共卫生问题。尽管许多研究的作者已经研究了自杀的神经生物学方面，但与自杀行为相关的分子机制仍不清楚。脑源性神经营养因子（BDNF）是最重要的神经营养因子之一，与受体酪氨酸激酶B（trkB）结合并激活后，直接参与大脑中的许多生理功能，包括细胞存活和突触可塑性。本研究旨在检查自杀者（以下简称自杀受试者）死后大脑中BDNF和/或trkB亚型的表达是否改变，以及这些改变是否与特定的精神病理状况相关。
这些研究在27名自杀受试者和21名非精神科对照受试者的前额叶皮质（Brodmann 9区）和海马体中进行。分别用竞争性逆转录聚合酶链反应和蛋白质印迹技术测定BDNF和trkB的信使核糖核酸水平和蛋白质水平。还在这些脑区测定了作为神经元标志物的神经元特异性烯醇化酶信使核糖核酸水平。
与对照受试者相比，自杀受试者前额叶皮质和海马体中BDNF和trkB的信使核糖核酸水平均显著降低，且与神经元特异性烯醇化酶水平无关。这些降低与BDNF和全长trkB的蛋白质水平显著降低有关，但与trkB的截短亚型无关。这些变化在所有自杀受试者中均存在，与精神科诊断无关，且与死后间隔、年龄、性别或脑pH值无关。
鉴于BDNF在介导包括细胞存活和突触可塑性在内的生理功能中的重要性，我们在自杀受试者死后大脑中发现BDNF和trkB表达降低，表明这些分子可能在自杀行为的病理生理方面起重要作用。
