Eero Castrén: BDNF-TRKB signaling and neuronal plasticity as the target of antidepressant drugs

Abstract

Neuronal plasticity has for a long time been considered important for the recovery from depression and for the antidepressant drug action, but how the drug action is translated to plasticity has remained unclear. Brain-derived neurotrophic factor (BDNF) and its receptor TRKB are critical regulators of neuronal plasticity and have been implicated in the antidepressant action. We have recently found that many, if not all, different antidepressants, including serotonin selective SSRIs, tricyclic as well as fast-acting ketamine and its metabolite hydroxynorketamine, directly bind to TRKB, thereby promoting TRKB translocation to synaptic membranes, which increases BDNF signaling.

We have further found that activation of TRKB receptors in parvalbumin-containing interneurons orchestrates cortical activation states and is both necessary and sufficient for the antidepressant-induced cortical plasticity.  Our findings open a new framework how the action of antidepressants act: rather that regulating brain monoamine concentrations, antidepressants directly bind to TRKB and allosterically promote BDNF signaling, thereby inducing a state of plasticity that allows re-wiring of abnormal networks for better functionality.

The talk will be held online via Zoom

Meeting ID and password will be sent with e-mail invitation. You can also send an e-mail to katja.kukatz@bcf.uni-freiburg.de for meeting ID and password.

More about the speaker and his research:

Eero Castrén