Classical and rapid-acting antidepressants increase TRKB turnover in dendritic spines

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http://urn.fi/URN:NBN:fi:hulib-201909273550
Title: Classical and rapid-acting antidepressants increase TRKB turnover in dendritic spines
Author: Moliner, Rafael
Other contributor: Helsingin yliopisto, Bio- ja ympäristötieteellinen tiedekunta, Bio- ja ympäristötieteellinen tiedekunta
University of Helsinki, Faculty of Biological and Environmental Sciences, Faculty of Biological and Environmental Sciences
Helsingfors universitet, Bio- och miljövetenskapliga fakulteten, Bio- och miljövetenskapliga fakulteten
Publisher: Helsingin yliopisto
Date: 2019
Language: eng
URI: http://urn.fi/URN:NBN:fi:hulib-201909273550
http://hdl.handle.net/10138/305791
Thesis level: master's thesis
Discipline: fysiologia ja neurotiede
Physiology and Neuroscience
fysiologi och neurovetenskap
Abstract: Classical and rapid-acting antidepressant drugs have been shown to reinstate juvenile-like plasticity in the adult brain, allowing mature neuronal networks to rewire in an environmentally-driven/activity-dependent process. Indeed, antidepressant drugs gradually increase expression of brain-derived neurotrophic factor (BDNF) and can rapidly activate signaling of its high-affinity receptor TRKB. However, the exact mechanism of action underlying drug-induced restoration of juvenile-like plasticity remains poorly understood. In this study we first characterized acute effects of classical and rapid-acting antidepressant drugs on the interaction between TRKB and postsynaptic density (PSD) proteins PSD-93 and PSD-95 in vitro. PSD proteins constitute the core of synaptic complexes by anchoring receptors, ion channels, adhesion proteins and various signaling molecules, and are also involved in protein transport and cell surface localization. PSD proteins have in common their role as key regulators of synaptic structure and function, although PSD-93 and PSD-95 are associated with different functions during development and have opposing effects on the state of plasticity in individual synapses and neurons. Secondly, we investigated changes in mobility of TRKB in dendritic structures in response to treatment with antidepressant drugs in vitro. We found that antidepressant drugs decrease anchoring of TRKB with PSD-93 and PSD-95, and can rapidly increase TRKB turnover in dendritic spines. Our results contribute to the mechanistic model explaining drug-induced restoration of juvenile-like neuronal plasticity, and may provide a common basis for the effects of antidepressant drugs.
Subject: depression
antidepressant
rapid-acting
plasticity
neurotrophin
BDNF
TRKB
PSD-93
PSD-95
iPlasticity
fluoxetine
ketamine
anchoring
interaction
uncoupling
disruption
synaptic complex
trafficking
dendrite
spine
synapse


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