TrkB neurotrophin receptor at the core of antidepressant effects, but how?

Brain-derived neurotrophic factor (BDNF) and its receptor TrkB have been studied for decades in mood disorders and their treatments. Various antidepressant drugs increase BDNF synthesis in the cortex, promoting neurotrophic processes and heightened plasticity. Induction of BDNF-TrkB signaling is also linked to ketamine and some anesthetics, even those without known antidepressant effects. Both ketamine and conventional antidepressants rapidly activate TrkB receptor signaling in the brain, while electroconvulsive therapy (ECT), a potent BDNF inducer, has not been clearly shown to produce such acute TrkB effects. Antidepressant regulation of TrkB signaling is developmentally regulated and requires an intact central nervous system. This review highlights peculiarities in how ketamine, classical antidepressants, and BDNF affect TrkB signaling.

Study at a glance

Abstract

The role of brain-derived neurotrophic factor (BDNF) and its receptor TrkB has been studied in the context of mood disorders and their treatments for a couple of decades. Pharmacologically diverse antidepressant drugs increase the synthesis of BDNF in the cortex (and some subcortical structures) and this effect accounts for their ability to facilitate neurotrophic processes eventually leading into heightened plasticity within the cortex. Induction of BDNF-TrkB signaling has also been associated with the mechanism of action of ketamine and more recently with some other anesthetics, even with ones not thought to possess antidepressant potential. Notably, both ketamine and conventional antidepressants activate TrkB receptor and its downstream signaling rapidly within the same time scale in the brain while electroconvulsive therapy (ECT), among the most potent inducers of BDNF, has not been unequivocally shown to produce such acute effects on TrkB. The ability of antidepressants to regulate TrkB signaling is developmentally regulated and requires an intact central nervous system. The purpose of this review is to highlight and discuss some of these peculiarities associated with the effects of ketamine and classical antidepressants and BDNF on TrkB signaling.