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Título: | Post-transcriptional modulation of serotonin transporter as a new target for antidepressant therapy |
Autor: | Bortolozzi, Analía CSIC ORCID; Ferrés-Coy, Albert CSIC; Pilar-Cuéllar, Fuencisla CSIC ORCID; Vidal, R.; Paz, Verónica CSIC ORCID; Cortés, Roser CSIC ORCID; Masana, Mercè CSIC ORCID; Valdizán, Elsa M. CSIC ORCID; Pazos, Ángel CSIC ORCID; Artigas, Francesc CSIC ORCID | Fecha de publicación: | 17-jul-2012 | Citación: | 8th FENS (2012) | Resumen: | Identifying the factors contributing to the etiology of anxiety and depression is critical for the development of more efficacious therapies. Serotonin (5-HT) is linked to both disorders. Current antidepressants, which block the serotonin transporter (SERT), show limited efficacy and slow onset of action. Here, we used a small interference RNA (siRNA) strategy to examine the biological consequences of reducing SERT expression, as previously reported for 5-HT1A-autoreceptor. Adult mice were locally infused with vehicle, nonsense-siRNA and SERT-siRNA into dorsal raphe nucleus (DR). The functional effects of SERT-siRNA knockdown were compared with those produced by chronic treatment with classical fluoxetine. Local SERT-siRNA infusion for 4-days suppressed SERT expression in DR (40%). This was accompanied by a selective and widespread reduction of SERT-binding sites throughout the brain. Moreover, a 4-day regimen with intra-DR SERT-siRNA modified brain variables considered to be key markers of antidepressant action, such as: a) reduced expression and sensitivity of 5-HT1A-autoreceptors, b) augmented 5-HT extracellular in DR-projecting areas such as striatum and hippocampus, c) increased hippocampal neurogenesis and d) increased plasticity-associated gene expression (BDNF, VEGF and ARC). In contrast, a 4-day regimen with fluoxetine did not alter any of these variables and only started to modify them after 15-day treatments. These findings highlight the critical role of SERT in the control of serotonergic function, including serotonin-mediated neural plasticity. They also support the use of siRNA targeting serotonergic genes (SERT, 5-HT1A-autoreceptor) as a new generation of antidepressant therapies with a potential greater efficacy faster onset of action than current treatments. | Descripción: | Póster presentado en: 8th FENS (Forum of Neuroscience), celebrado del 14 al 18 de julio de 2012 en Barcelona (España) | URI: | http://hdl.handle.net/10261/113005 |
Aparece en las colecciones: | (IIBB) Comunicaciones congresos |
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