Abstract
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.
Highlights
Brain-derived neurotrophic factor (BDNF) is under a pivotal role in the psychiatric disorders, including alcohol dependence[1,2,3]
ProBDNF/p75 neurotrophin receptor (p75NTR)/sortilin signalling was activated in patients with alcohol dependence ProBDNF preferentially binds to its co-receptors (p75NTR and sortilin) to perform the cascade roles in neuronal apoptosis
The above results suggest that proBDNF, p75NTR and sortilin were activated in patients with alcohol dependence
Summary
Brain-derived neurotrophic factor (BDNF) is under a pivotal role in the psychiatric disorders, including alcohol dependence[1,2,3]. How the genetic and environmental factors interact to promote the pathogenesis of alcohol dependence requires further investigations. Human alcoholics, in both men and women show a significant volume loss (shrinkage) in cortical and subcortical brain structures, which include both grey and white matters. ProBDNF and mBDNF play different, even opposite roles in neuronal survival, differentiation and plasticity[9]. Many studies show that mBDNF and its high-affinity receptor, tyrosine kinase receptor (TrkB), play pivotal roles in mediating neuronal survival and
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