The precurser of brain-derived neurotrophic factor (proBDNF) is proteolytically cleaved into mature BDNF (mBDNF) by tPA and by plasmin (the end product of tPA)16 and promotes neuronal apoptosis and long-term depression, while mBDNF has anti-apoptotic properties and favors long-term potentiation.17 Moreover, physical exercise has antidepressant effects and increases tPA and mBDNF levels.12 The inability to convert proBDNF into mBDNF is associated with depression pathogenesis and, consequently, mBDNF is implicated in the mechanism of action of antidepressants.18 This evidence concerns the gene PLG and depressive disorder.