Buscar

Estamos realizando la búsqueda. Por favor, espere...

 Detalle_Publicacion

Therapeutic antidepressant potential of a conjugated siRNA silencing the serotonin transporter after intranasal administration

Abstract: Major depression brings about a heavy socio-economic burden worldwide due to its high prevalence and the low efficacy of antidepressant drugs, mostly inhibiting the serotonin transporter (SERT). As a result, ~80% of patients show recurrent or chronic depression, resulting in a poor quality of life and increased suicide risk. RNA interference (RNAi) strategies have been preliminarily used to evoke antidepressant-like responses in experimental animals. However, the main limitation for the medical use of RNAi is the extreme difficulty to deliver oligonucleotides to selected neurons/systems in the mammalian brain. Here we show that the intranasal administration of a sertraline-conjugated small interfering RNA (C-SERT-siRNA) silenced SERT expression/function and evoked fast antidepressant-like responses in mice. After crossing the permeable olfactory epithelium, the sertraline-conjugated-siRNA was internalized and transported to serotonin cell bodies by deep Rab-7-associated endomembrane vesicles. Seven-day C-SERT-siRNA evoked similar or more marked responses than 28-day fluoxetine treatment. Hence, C-SERT-siRNA (i) downregulated 5-HT1A-autoreceptors and facilitated forebrain serotonin neurotransmission, (ii) accelerated the proliferation of neuronal precursors and (iii) increased hippocampal complexity and plasticity. Further, short-term C-SERT-siRNA reversed depressive-like behaviors in corticosterone-treated mice. The present results show the feasibility of evoking antidepressant-like responses by selectively targeting neuronal populations with appropriate siRNA strategies, opening a way for further translational studies.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Mol Psychiatry. 2016 Mar;21(3):328-38

Editorial: Nature Publishing Group Specialist Journals

 Año de publicación: 2016

Nº de páginas: 11

Tipo de publicación: Artículo de Revista

ISSN: 1359-4184,1476-5578

Autoría

FERRES COY, A

GALOFRÉ, M

RUIZ BRONCHAL, E

CAMPA, L

LEZA, JC

ALVARADO, G

MONTEFELTRO, A

ELSA MARIA VALDIZAN RUIZ

ARTIGAS, F

BORTOLOZZI, A