RNAi-mediated serotonin transporter suppression rapidly increases serotonergic neurotransmission and hippocampal neurogenesis

Current antidepressants, which inhibit the serotonin transporter (SERT), display limited efficacy and slow onset of action. Here, we show that partial reduction of SERT expression by small interference RNA (SERT-siRNA) decreased immobility in the tail suspension test, displaying an antidepressant po...

Full description

Bibliographic Details
Authors: Ferrés Coy, Albert, Pilar Cuéllar, Fuencisla, Vidal, Raquel, Paz, Verónica, Masana Nadal, Mercè, Cortés, Roser, Carmona, M.C., Campa, Leticia, Pazos, Ángel, Montefeltro, Andrés, Valdizán, Elsa M., Artigas Pérez, Francesc, Bortolozzi Biasoni, Analía
Format: article
Status:Published version
Publication Date:2013
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/206595
Online Access:https://hdl.handle.net/2445/206595
Access Level:Open access
Keyword:Depressió psíquica
Antidepressius
Receptors de serotonina
Neurones
Mental depression
Antidepressants
Serotonin receptors
Neurons
Description
Summary:Current antidepressants, which inhibit the serotonin transporter (SERT), display limited efficacy and slow onset of action. Here, we show that partial reduction of SERT expression by small interference RNA (SERT-siRNA) decreased immobility in the tail suspension test, displaying an antidepressant potential. Moreover, short-term SERT-siRNA treatment modified mouse brain variables considered to be key markers of antidepressant action: reduced expression and function of 5-HT(1A)-autoreceptors, elevated extracellular serotonin in forebrain and increased neurogenesis and expression of plasticity-related genes (BDNF, VEGF, Arc) in hippocampus. Remarkably, these effects occurred much earlier and were of greater magnitude than those evoked by long-term fluoxetine treatment. These findings highlight the critical role of SERT in serotonergic function and show that the reduction of SERT expression regulates serotonergic neurotransmission more potently than pharmacological blockade of SERT. The use of siRNA-targeting genes in serotonin neurons (SERT, 5-HT(1A)-autoreceptor) may be a novel therapeutic strategy to develop fast-acting antidepressants.

Similar Items