Neuronal release of proBDNF

ProBDNF can have drastic effects on synaptic function that are quite different from those of mature BDNF. It is, however, controversial whether proBDNF is ever released in amounts that are sufficient to affect normal synaptic plasticity. Here, Yang and colleagues have detected the release of proBDNF from hippocampal neurons using newly developed knock-in mice and antibodies. Pro–brain-derived neurotrophic factor (proBDNF) and mature BDNF utilize distinct receptors to mediate divergent neuronal actions. Using new tools to quantitate endogenous BDNF isoforms, we found that mouse neurons secrete both proBDNF and mature BDNF. The highest levels of proBDNF and p75 were observed perinatally and declined, but were still detectable, in adulthood. Thus, BDNF actions are developmentally regulated by secretion of proBDNF or mature BDNF and by local expression of p75 and TrkB.