Deciphering the Role of the PAI_1-mBDNF Pathway in Alcohol Use Disorder: Insights into Pathogenesis and Abstinence Treatment Efficacy

Abstract The pathway of plasminogen activator inhibitor-1 (PAI_1) -brain-derived neurotrophic factor (BDNF) plays a pivotal role in the conversion of Probrain-derived neurotrophic factor (ProBDNF) to mature BDNF (mBDNF), yet its clinical relevance in patients with alcohol use disorder remains understudied (AUD). Enzyme-linked immunosorbent assay (ELISA) was applied to examine the relevant protein levels of the PAI_1-mBDNF pathway in plasma samples from three groups of subjects, and statistical analysis was performed using ANOVA and One-Way Repeated Measures ANOVA. Our findings unveil significant alterations induced by alcohol consumption: (1) A marked decrease in tissue plasminogen activator (tPA), mBDNF, and tropomyosin receptor kinase B (TrkB), while significantly increasing the levels of PAI_1, ProBDNF, and P75 neurotrophin receptor (P75NTR), and inhibiting the conversion of ProBDNF to mBDNF. (2) Following abstinence treatment, the levels of tPA, mBDNF, and TrkB in the AUD group significantly increased, while the levels of PAI_1, ProBDNF, and P75NTR significantly decreased, promoting the conversion of ProBDNF to mBDNF. These clinical research outcomes collectively suggest that alcohol suppresses that alcohol inhibits the conversion of ProBDNF to mBDNF, while the generation of mBDNF significantly increases after abstinence treatment. The PAI_1-mBDNF cleavage pathway may be associated with alcohol use disorder and abstinence treatment.