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死后大脑中 BDNF/TrkB 和 NGF/TrkA 水平与重度抑郁症和自杀的关联。

Association of BDNF / TrkB and NGF / TrkA Levels in Postmortem Brain with Major Depression and Suicide.

机构信息

Inonu University, Department of Psychiatry, Malatya, 44280, Turkey,

出版信息

Psychiatr Danub. 2021 Winter;33(4):491-498. doi: 10.24869/psyd.2021.491.

DOI:10.24869/psyd.2021.491
PMID:34928896
Abstract

BACKGROUND

Suicide Attempts are the main complications of Major Depressive Episodes and are difficult to predict. There is still a lack of knowledge about its neurochemical aspects. There is increasing evidence that Brain-derived neurotrophic factor (BDNF) and Nerve growth factor (NGF) play a role in the pathophysiology and treatment of depression by binding and activating cognate receptors Tyrosine Kinase B (TrkB) and Tyrosie Kinase A (TrkA), respectively. This study was conducted to examine whether BDNF and / or TrkB as well as NGF and / or TrkA expression profiles were changed in the hippocampus of postmortem brain of individuals with depression who committed suicide.

SUBJECTS AND METHODS

This study was conducted with the brain tissue of 61 victims who died as a result of suicide due to depression and 25 people who died due to traffic accidents. The psychiatric history of the cases was determined by the psychological autopsy method. Samples were taken from the hippocampus region of the brain at the forensic medicine institution. After storage under appropriate conditions, protein and mRNA levels of BDNF, TrkB, NGF and TrkA were determined in the genetics laboratory.

RESULTS

Average age of the suicide group was 30 and the average age of the control group was 24.5. The suicide group consisted of 70.5% male and 29.5% female cases. There was no significant difference between the groups in terms of age (p=0.062) and gender (p=0.718). BDNF, NGF, TrkA and TrkB values were found to be lower in the suicide group compared to the control group and there was a significant difference between the groups (p≤0.001; p=0.001; p=0.001; p=0.011).

CONCLUSION

Given the importance of BDNF and NGF and their cognate receptors in mediating physiological functions, including cell survival and synaptic plasticity, our findings regarding decreased expression of BDNF, TrkB, NGF and TrkA in both protein and mRNA levels of postmortem brains of suicide victims suggests that it may play an important role in the pathophysiological aspects of its behavior. Further studies in this context may be useful both in understanding the molecular basis of suicide and in designing therapeutic models targeting these molecular pathways.

摘要

背景

自杀企图是重度抑郁发作的主要并发症,且难以预测。目前对于其神经化学方面的认识仍存在不足。越来越多的证据表明,脑源性神经营养因子(BDNF)和神经生长因子(NGF)通过与相应的受体酪氨酸激酶 B(TrkB)和酪氨酸激酶 A(TrkA)结合并激活,在抑郁症的病理生理学和治疗中发挥作用。本研究旨在探讨自杀的抑郁症患者死后海马脑中 BDNF 和/或 TrkB 以及 NGF 和/或 TrkA 的表达谱是否发生改变。

对象与方法

本研究采用了因抑郁症自杀死亡的 61 名受害者和因交通事故死亡的 25 名受害者的脑组织。通过心理解剖法确定病例的精神病史。在法医机构从大脑海马区采集样本。在遗传学实验室中确定 BDNF、TrkB、NGF 和 TrkA 的蛋白质和 mRNA 水平。

结果

自杀组的平均年龄为 30 岁,对照组的平均年龄为 24.5 岁。自杀组中 70.5%为男性,29.5%为女性。两组在年龄(p=0.062)和性别(p=0.718)方面无显著差异。与对照组相比,自杀组的 BDNF、NGF、TrkA 和 TrkB 值较低,组间差异有统计学意义(p≤0.001;p=0.001;p=0.001;p=0.011)。

结论

鉴于 BDNF 和 NGF 及其相应受体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,我们发现自杀受害者死后大脑中 BDNF、TrkB、NGF 和 TrkA 的蛋白和 mRNA 表达水平降低,这表明它们可能在其行为的病理生理方面发挥重要作用。在这方面进一步的研究可能有助于理解自杀的分子基础,并设计针对这些分子途径的治疗模型。

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