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...

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Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/206595
Acceso en línea:https://hdl.handle.net/2445/206595
Access Level:acceso abierto
Palabra clave:Depressió psíquica
Antidepressius
Receptors de serotonina
Neurones
Mental depression
Antidepressants
Serotonin receptors
Neurons
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spelling RNAi-mediated serotonin transporter suppression rapidly increases serotonergic neurotransmission and hippocampal neurogenesisFerrés Coy, AlbertPilar Cuéllar, FuencislaVidal, RaquelPaz, VerónicaMasana Nadal, MercèCortés, RoserCarmona, M.C.Campa, LeticiaPazos, ÁngelMontefeltro, AndrésValdizán, Elsa M.Artigas Pérez, FrancescBortolozzi Biasoni, AnalíaDepressió psíquicaAntidepressiusReceptors de serotoninaNeuronesMental depressionAntidepressantsSerotonin receptorsNeuronsCurrent 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.Nature Publishing Group2013info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/206595Articles publicats en revistes (Biomedicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a:Translational Psychiatry, 2013, vol. 3cc-by-nc-nd (c) A Ferrés Coy et al., 2013http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2065952026-05-27T06:46:51Z
dc.title.none.fl_str_mv RNAi-mediated serotonin transporter suppression rapidly increases serotonergic neurotransmission and hippocampal neurogenesis
title RNAi-mediated serotonin transporter suppression rapidly increases serotonergic neurotransmission and hippocampal neurogenesis
spellingShingle RNAi-mediated serotonin transporter suppression rapidly increases serotonergic neurotransmission and hippocampal neurogenesis
Ferrés Coy, Albert
Depressió psíquica
Antidepressius
Receptors de serotonina
Neurones
Mental depression
Antidepressants
Serotonin receptors
Neurons
title_short RNAi-mediated serotonin transporter suppression rapidly increases serotonergic neurotransmission and hippocampal neurogenesis
title_full RNAi-mediated serotonin transporter suppression rapidly increases serotonergic neurotransmission and hippocampal neurogenesis
title_fullStr RNAi-mediated serotonin transporter suppression rapidly increases serotonergic neurotransmission and hippocampal neurogenesis
title_full_unstemmed RNAi-mediated serotonin transporter suppression rapidly increases serotonergic neurotransmission and hippocampal neurogenesis
title_sort RNAi-mediated serotonin transporter suppression rapidly increases serotonergic neurotransmission and hippocampal neurogenesis
dc.creator.none.fl_str_mv 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
author Ferrés Coy, Albert
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Depressió psíquica
Antidepressius
Receptors de serotonina
Neurones
Mental depression
Antidepressants
Serotonin receptors
Neurons
topic Depressió psíquica
Antidepressius
Receptors de serotonina
Neurones
Mental depression
Antidepressants
Serotonin receptors
Neurons
description 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.
publishDate 2013
dc.date.none.fl_str_mv 2013
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/206595
url https://hdl.handle.net/2445/206595
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a:
Translational Psychiatry, 2013, vol. 3
dc.rights.none.fl_str_mv cc-by-nc-nd (c) A Ferrés Coy et al., 2013
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) A Ferrés Coy et al., 2013
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,198674

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