TrkB is a receptor tyrosine kinase of the Trk family. It is activated by brain-derived neurotrophic factor (BDNF), neurotrophin-3, -4 and -5 and is involved in the development and maintenance of the nervous system¹. TrkB-Fc is a fusion protein combining the extracellular binding domain of TrkB and the Fc domain of human IgG. TrkB-Fc is a tool for studying the biological actions of BDNF ².

A large number of in vitro studies support the notion that TrkB-Fc inhibits BDNF activity³. Addition of TrkB-Fc to hippocampal and cortical slices and cultured cortical, striatal, and dentate granule cells either abolishes or opposes the effect of BDNF. The TrkB-Fc fusion protein, a specific inhibitor of Trk kinase activity, K252, and a TrkB neutralizing antibody all have similar BDNF-blocking effects. In addition, administration of TrkB-Fc in vivo has consequences that are in accordance with decreased BDNF activity. Systemic nerve growth factor treatment, which leads to a condition resembling peripheral inflammation, raises BDNF levels in sensory neurons and increases nociceptive spinal reflex excitability. This increased central excitability is reduced by TrkB-Fc⁴. Moreover, intraventricular delivery of TrkB-Fc suppresses epileptogenesis, similar to what has been observed in heterozygous BDNF knockout mice and in transgenic mice overexpressing truncated TrkB receptors and with decreased endogenous BDNF levels⁵. In contrast to these data, Croll et al.² reported that TrkB-Fc can potentiate BDNF-induced TrkB phosphorylation. However, this effect was observed only when TrkB-Fc and BDNF were coinfused intracerebrally in equimolar concentrations.