Rethinking the role of TRKB in the action of antidepressants and psychedelics.
Cecilia Anna Brunello, Cecilia Cannarozzo, Eero Castrén
Trends in Neurosciences November 1, 2024 DOI: 10.1016/j.tins.2024.08.011 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | Depression Ketamine Neuroplasticity |
| Keywords | Bdnf Allosteric modulators Parvalbumin interneurons Psychopharmacology Mental health Depression treatment |
| Citations | 29 |
| Key points | Proposes that some antidepressants may directly bind to TRKB and allosterically potentiate BDNF signaling, and that activating TRKB in parvalbumin-containing interneurons disinhibits cortical networks and reactivates a juvenile-like plasticity window, which may underlie clinical antidepressant effects. |
Abstract
Antidepressant drugs promote neuronal plasticity, and activation of brain-derived neurotrophic factor (BDNF) signaling through its receptor neuronal receptor tyrosine kinase 2 (NTRK2 or TRKB) is among the critical steps in this process. These mechanisms are shared by typical slow-acting antidepressants, fast-acting ketamine, and psychedelic compounds, although the cellular targets of each drug differ. In this opinion article, we propose that some of these antidepressants may directly bind to TRKB and allosterically potentiate BDNF signaling, among other possible effects. TRKB activation in parvalbumin-containing interneurons disinhibits cortical networks and reactivates a juvenile-like plasticity window. Subsequent rewiring of aberrant networks, coupled with environmental stimuli, may underlie its clinical antidepressant effects. The end-to-end hypothesis proposed may stimulate the search for new treatment strategies.