The serum protein levels of the tPA-BDNF pathway are implicated in depression and antidepressant treatment.
The serum protein levels of the tPA-BDNF pathway are implicated in depression and antidepressant treatment.
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tPA-BDNF 通路的血清蛋白水平与抑郁症和抗抑郁治疗有关
DOI：
10.1038/tp.2017.43
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发表时间：
2017-04-04
影响因子：
6.8
通讯作者：
Yuan Y
中科院分区：
文献类型：
--
作者：
Jiang H;Chen S;Li C;Lu N;Yue Y;Yin Y;Zhang Y;Zhi X;Zhang D;Yuan Y
脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）在抑郁症（major depression disorder，MDD）的发病机制中起着重要作用。前体BDNF（proBDNF）和成熟BDNF（mBDNF）在神经可塑性方面具有相反的生物学效应，组织型纤溶酶原激活物（tPA）/纤溶酶系统在proBDNF向mBDNF的裂解过程中起着关键作用。然而，关于tPA-BDNF通路在MDD中的作用知之甚少。我们采用夹心ELISA（酶联免疫吸附试验）方法检测了35名无药物抑郁症患者在艾司西酞普兰（平均12.5 mg/d）或度洛沙坦（平均64 mg/d）治疗8周前后和35名健康对照者血清中tPA-BDNF通路的蛋白浓度，包括tPA、BDNF、原肌球蛋白受体激酶B（Trk B）、proBDNF和p75 NTR。MDD患者血清tPA、BDNF及BDNF/proBDNF比值均显著低于对照组，而TrkB、proBDNF及其受体p75 NTR均显著高于对照组。治疗8周后，tPA、BDNF、proBDNF及BDNF/proBDNF比值均逆转，但p75 NTR较基线升高，TrkB无明显变化。tPA、BDNF、TrkB、proBDNF和p75 NTR均产生相当好或优异的诊断性能（受试者工作特征曲线（AUC）下的面积>0.8或0.9）。这五种蛋白的组合表现出更好的诊断效果（AUC：0.977）和足够的敏感性和特异性分别为88.1%和92.7%。我们的研究结果表明，tPA-BDNF裂解途径可能涉及MDD的发病机制和抗抑郁治疗作用的机制。tPA、BDNF、TrkB、proBDNF和p75 NTR的组合可以提供MDD的诊断生物标志物组。
Evidence demonstrates that brain-derived neurotrophic factor (BDNF) has a pivotal role in the pathogenesis of major depressive disorder (MDD). Precursor-BDNF (proBDNF) and mature BDNF (mBDNF) have opposing biological effects in neuroplasticity, and the tissue-type plasminogen activator (tPA)/plasmin system is crucial in the cleavage processing of proBDNF to mBDNF. However, very little is known about the role of the tPA–BDNF pathway in MDD. We examined serum protein concentrations in the tPA–BDNF pathway, including tPA, BDNF, tropomyosin receptor kinase B (TrkB), proBDNF and p75NTR, obtained from 35 drug-free depressed patients before and after 8 weeks of escitalopram (mean 12.5 mg per day) or duloxetine (mean 64 mg per day) treatment and 35 healthy controls using sandwich ELISA (enzyme-linked immunosorbent assay) methods. Serum tPA and BDNF and the ratio of BDNF/proBDNF were significantly lower in the MDD patients than in controls, whereas TrkB, proBDNF and its receptor p75NTR were higher. After 8 weeks of treatment, tPA, BDNF and proBDNF and the BDNF/proBDNF ratio were reversed, but p75NTR was higher than baseline, and TrkB was not significantly changed. tPA, BDNF, TrkB, proBDNF and p75NTR all yielded fairly good or excellent diagnostic performance (area under the receiver operating characteristic curve (AUC) >0.8 or 0.9). Combination of these five proteins demonstrated much better diagnostic effectiveness (AUC: 0.977) and adequate sensitivity and specificity of 88.1% and 92.7%, respectively. Our results suggest that the tPA–BDNF lysis pathway may be implicated in the pathogenesis of MDD and the mechanisms underlying antidepressant therapeutic action. The combination of tPA, BDNF, TrkB, proBDNF and p75NTR may provide a diagnostic biomarker panel for MDD.