English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/163453
Título

Antidepressants induce autophagy dependent-NLRP3-inflammasome inhibition in Major depressive disorder

AutorAlcocer-Gómez, Elísabet; Casas-Barquero, Nieves; Bullón, Pedro; Sánchez-Alcázar, José Antonio ; Cordero, Mario D.
Palabras claveNLRP3-inflammasome
Antidepressants
Autophagy
Major depressive disorder
Fecha de publicación2017
EditorElsevier
CitaciónPharmacological Research 121: 114-121 (2017)
ResumenMajor 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.
Descripciónet al.
URIhttp://hdl.handle.net/10261/163453
Identificadoresdoi: 10.1016/j.phrs.2017.04.028
e-issn: 1096-1186
issn: 1043-6618
Aparece en las colecciones: (CABD) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
accesoRestringido.pdf15,38 kBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.