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| Título: | Antidepressants induce autophagy dependent-NLRP3-inflammasome inhibition in Major depressive disorder |
Autor: | Alcocer-Gómez, Elísabet; Casas-Barquero, Nieves; Bullón, Pedro CSIC ORCID; Sánchez-Alcázar, José Antonio CSIC ORCID ; Cordero, Mario D. CSIC ORCID | Palabras clave: | NLRP3-inflammasome Antidepressants Autophagy Major depressive disorder |
Fecha de publicación: | 2017 | Editor: | Elsevier | Citación: | Pharmacological Research 121: 114-121 (2017) | Resumen: | Major Depressive Disorder (MDD, ICD-10: F-33) is a prevalent illness in which the pathogenic mechanism remains elusive. Recently an important role has been attributed to neuro-inflammation, and specifically the NLRP3-inflammasome complex, in the pathogenesis of MDD. This suggests a key role for immunomodulation as a key pathway in the treatment of this disorder. This study evaluates the involvement of nine common antidepressants in the NLRP3-inflammasome complex (fluoxetine, paroxetine, mianserin, mirtazapine, venlafaxine, desvenlafaxine, amitriptyline, imipramine and agomelatine), both in in vitro THP-1 cells stimulated by ATP, and in a stress-induced depressive animal or MDD patients. Antidepressant treatment induced inflammasome inhibition was observed by decreased serum levels of IL-1β and IL-18 and decrease of NLRP3 and IL-1β (p17) protein expression. This was also observed under stress-induced depressive behaviour and inflammasome activation in C57Bl/6 mice in vivo. Deletion of key autophagy mediator Atg5 in embryonic fibroblasts (MEF cells) showed an autophagy dependent-NLRP3-inflammasome inhibition by antidepressant treatment. These results suggest the NLRP3-inflammasome could be a biomarker for antidepressant treatment response in MDD patients, and therefore the monitoring of NLRP3 expression levels and/or IL-1β/IL-18 release may have clinical value in drug selection. Existing evidence suggests an anti-inflammatory effect of some antidepressants shown by IL-1β, IL-6 and TNF-α. Our data have shown that antidepressant-mediated autophagy may have a role in restoration of certain metabolic and immunological pathways in MDD patients. | Descripción: | et al. | URI: | http://hdl.handle.net/10261/163453 | DOI: | 10.1016/j.phrs.2017.04.028 | Identificadores: | doi: 10.1016/j.phrs.2017.04.028 e-issn: 1096-1186 issn: 1043-6618 |
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