Hrdina P, Faludi G, Li Q, Bendotti C, Tekes K, Sotonyi P, Palkovits M
Department of Pharmacology, Royal Ottawa Hospital, Faculty of Medicine, University of Ottawa, Ontario, Canada.
Mol Psychiatry. 1998 Sep;3(5):411-8. doi: 10.1038/sj.mp.4000435.
The aim of this study was to investigate whether the previously observed adaptive changes in the monoaminergic receptors in post-mortem brains of depressed suicide victims are associated with alteration in some functional proteins involved in serotonergic neuronal signalling, namely PKC and GAP-43. Selected regions from ten brains of antidepressant-free depressed suicide victims and ten matched controls were used to examine the levels of GAP-43 protein, GAP-43 mRNA and PKC isoenzymes by Western blotting with monoclonal antibodies specific for these proteins. A major finding of the study was a significant decrease in GAP-43 protein levels and its mRNA expression in prefrontal cortex (BA9) (by 24% and 34%, respectively) of suicide brains compared to controls. No significant changes were found in GAP-43 protein or its mRNA in frontopolar cortex (BA10), amygdala, substantia nigra or putamen. Levels of PKC isoenzymes had a heterogenous regional distribution but were not significantly altered in any of the regions examined. Given the role of GAP-43 in the establishment and reorganization of synaptic connections, the finding of selective reduction of this protein in prefrontal cortex suggests that a dysfunctional synaptic organization in this region may be associated with depression and suicidal behaviour. This study provides the first evidence of an alteration in a protein related to the neuronal plasticity in the brain of depressed suicide victims.
本研究的目的是调查先前在抑郁自杀受害者的尸检大脑中观察到的单胺能受体的适应性变化是否与参与血清素能神经元信号传导的某些功能蛋白（即蛋白激酶C和GAP - 43）的改变有关。从十名未服用抗抑郁药的抑郁自杀受害者和十名匹配对照的大脑中选取特定区域，使用针对这些蛋白的单克隆抗体通过蛋白质印迹法检测GAP - 43蛋白、GAP - 43信使核糖核酸和蛋白激酶C同工酶的水平。该研究的一个主要发现是，与对照组相比，自杀者大脑前额叶皮质（BA9）中GAP - 43蛋白水平及其信使核糖核酸表达显著降低（分别降低24%和34%）。在额极皮质（BA10）、杏仁核、黑质或壳核中未发现GAP - 43蛋白或其信使核糖核酸有显著变化。蛋白激酶C同工酶水平在各区域分布不均，但在所检查的任何区域均未发生显著改变。鉴于GAP - 43在突触连接的建立和重组中的作用，前额叶皮质中该蛋白选择性减少的发现表明该区域功能失调的突触组织可能与抑郁和自杀行为有关。本研究首次提供了抑郁自杀受害者大脑中与神经元可塑性相关蛋白发生改变的证据。
