The Mental Hospital of Yunnan Province, Kunming, Yunnan Province, China.
Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, Yunnan Province, China.
Transl Psychiatry. 2018 Mar 9;7(11):2. doi: 10.1038/s41398-017-0015-4.
Alcohol dependence is a worldwide problem with a great social and economic burden in many countries. A number of studies have suggested that BDNF (mature BDNF) and its precursor (proBDNF) play important roles in the alcohol dependence. However, what roles of the mBDNF/proBDNF pathways play during the pathological process of alcohol dependence are not clearly understood. In our clinical study, peripheral blood was sampled from 30 male patients with alcohol dependence and 50 healthy males (as control). The protein levels of proBDNF, p75NTR, sortilin, mBDNF, TrkB and mRNA levels of BDNF, p75NTR, sortilin, and TrkB were detected in the peripheral blood in our study. We found that the protein levels of proBDNF and p75NTR were increased, but not the sortilin protein level; while the TrkB protein level was decreased in the alcohol dependence patients compared with healthy controls. Moreover, the mRNA levels of p75NTR and sortilin from the lymphocytes were slightly increased; while BDNF and TrkB were significantly decreased. The ELISA results of mBDNF and TrkB were declined in the alcohol dependence group. The levels of mBDNF and TrkB were negatively correlated with the average amount of daily ethanol consumption, and the levels of proBDNF, p75NTR and sortilin were positively correlated with the average amount of ethanol consumption per day. The ratio of proBDNF to mBDNF was altered in alcohol dependence patients. The balance between the proBDNF/p75NTR and mBDNF/TrkB signalling pathways appeared dysregulated in alcohol dependence. Our results suggested that both pathways may participate in the complex processes of alcohol dependence.
酒精依赖是一个全球性问题，在许多国家都带来了巨大的社会和经济负担。许多研究表明，BDNF（成熟 BDNF）及其前体（proBDNF）在酒精依赖中发挥重要作用。然而，mBDNF/proBDNF 途径在酒精依赖的病理过程中扮演什么角色尚不清楚。在我们的临床研究中，从 30 名男性酒精依赖患者和 50 名健康男性（作为对照）中抽取外周血。检测了外周血中 proBDNF、p75NTR、sortilin、mBDNF、TrkB 的蛋白水平以及 BDNF、p75NTR、sortilin 和 TrkB 的 mRNA 水平。我们发现，与健康对照组相比，酒精依赖患者的 proBDNF 和 p75NTR 蛋白水平升高，但 sortilin 蛋白水平没有升高；而 TrkB 蛋白水平降低。淋巴细胞中 p75NTR 和 sortilin 的 mRNA 水平略有升高；而 BDNF 和 TrkB 则明显下降。酒精依赖组 mBDNF 和 TrkB 的 ELISA 结果下降。mBDNF 和 TrkB 的水平与每天平均乙醇摄入量呈负相关，而 proBDNF、p75NTR 和 sortilin 的水平与每天平均乙醇摄入量呈正相关。酒精依赖患者 proBDNF/mBDNF 比值发生改变。proBDNF/p75NTR 和 mBDNF/TrkB 信号通路之间的平衡在酒精依赖中出现失调。我们的结果表明，这两条通路可能都参与了酒精依赖的复杂过程。
