AIMS: The NLRP3 inflammasome is a cytoplasmic multiprotein complex of the innate immune system that regulates the cleavage of interleukin-1β and interleukin-18 precursors. It can detect a wide range of danger signals and trigger a series of immune-inflammatory reactions. There were plenty of studies indicating that activation of the immune system played pivotal roles in depression. However, the underlying mechanisms of immune-depression interactions remained elusive and there was no report about the involvement of inflammasome activation in depression. METHODS: We established an acute depression mouse model with lipopolysaccharide to explore the involvement of inflammasome activation in depression. RESULTS: The lipopolysaccharide-treated mice displayed depressive-like behaviors and pro-inflammatory cytokine interleukin-1β protein and mRNA levels significantly increased. The NLRP3 inflammasome mRNA expression level also significantly elevated in depressed mice brain. Pretreatment with the NLRP3 inflammasome inhibitor Ac-YVAD-CMK significantly abrogated the depressive-like behaviors induced by lipopolysaccharide. CONCLUSION: These data suggest for the first time that the NLRP3 inflammasome is involved in lipopolysaccharide-induced mice depressive-like behaviors. The NLRP3 inflammasome may be a central mediator between immune activation and depression, which raises the possibility that it may be a more specific target for the depression treatments in the near future.
AIMS: The NLRP3 inflammasome is a cytoplasmic multiprotein complex of the innate immune system that regulates the cleavage of interleukin-1β and interleukin-18 precursors. It can detect a wide range of danger signals and trigger a series of immune-inflammatory reactions. There were plenty of studies indicating that activation of the immune system played pivotal roles in depression. However, the underlying mechanisms of immune-depression interactions remained elusive and there was no report about the involvement of inflammasome activation in depression. METHODS: We established an acute depressionmouse model with lipopolysaccharide to explore the involvement of inflammasome activation in depression. RESULTS: The lipopolysaccharide-treated mice displayed depressive-like behaviors and pro-inflammatory cytokine interleukin-1β protein and mRNA levels significantly increased. The NLRP3 inflammasome mRNA expression level also significantly elevated in depressed mice brain. Pretreatment with the NLRP3 inflammasome inhibitor Ac-YVAD-CMK significantly abrogated the depressive-like behaviors induced by lipopolysaccharide. CONCLUSION: These data suggest for the first time that the NLRP3 inflammasome is involved in lipopolysaccharide-induced micedepressive-like behaviors. The NLRP3 inflammasome may be a central mediator between immune activation and depression, which raises the possibility that it may be a more specific target for the depression treatments in the near future.
Authors: Philippe Leff-Gelman; Ismael Mancilla-Herrera; Mónica Flores-Ramos; Carlos Cruz-Fuentes; Juan Pablo Reyes-Grajeda; María Del Pilar García-Cuétara; Marielle Danitza Bugnot-Pérez; David Ellioth Pulido-Ascencio Journal: Neurosci Bull Date: 2016-07-18 Impact factor: 5.203
Authors: Albert E Towers; Maci L Oelschlager; Jay Patel; Stephen J Gainey; Robert H McCusker; Gregory G Freund Journal: Metabolism Date: 2017-03-09 Impact factor: 8.694
Authors: Elísabet Alcocer-Gómez; Cristina Ulecia-Morón; Fabiola Marín-Aguilar; Tatyana Rybkina; Nieves Casas-Barquero; Jesús Ruiz-Cabello; Bernhard Ryffel; Lionel Apetoh; François Ghiringhelli; Pedro Bullón; José Antonio Sánchez-Alcazar; Angel M Carrión; Mario D Cordero Journal: Mol Neurobiol Date: 2015-09-11 Impact factor: 5.590