La signalisation du Brain-Derived Neurotrophic Factor et ses récepteurs dans les plaquettes
The Brain-Derived Neutrophic Factor (BDNF) is a growth factor that was initially discovered in the brain. BDNF has both an autocrine and a paracrine role in neurons and its release and signaling mechanisms have been extensively studied in the central nervous system. Surprisingly, large quantities of BDNF have been reported in circulation, where it is essentially stored in platelets with concentrations reaching 100-1000-fold those of neurons. Despite this abundance, the function of BDNF in platelet biology has not been explored. Thus, this project sought to investigate the effect of BDNF on platelet function and the mechanisms underlying platelet responses to BDNF. In washed platelets, BDNF induced complete biphasic platelet aggregation that in part relied on amplification from secondary mediators. The low-affinity agonist neurotrophin-4 and an activating antibody raised against the canonical BDNF receptor TrkB induced similar platelet responses, implicating TrkB. Platelets express, both at their surface and in their intracellular compartment, a truncated form of TrkB lacking a tyrosine kinase domain. The BDNF-induced aggregation of washed platelets was prevented by inhibitors of the Rac1, PKC, and PI3K/Akt. Platelets exposed to BDNF secreted pro-angiogenic and pro-inflammatory cytokines, which may play a role in maintaining vascular homeostasis. Finally, in platelet-rich plasma, exogenous BDNF failed to induce aggregation and BDNF immunoprecipitates contained α2-macroglobulin immunoreactivity. Hence, platelets are rich in BDNF, which induce platelet aggregation via TrkB activation. The restriction of BDNF bioavailablility by plasma protein binding may serve to target BDNF-mediated platelet activation to sites of vascular injury.
BDNF Platelets Aggregation TrkB Tyrosine kinase Signaling