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Stress-Induced Depressive Behaviors Require a Functional NLRP3 Inflammasome

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Abstract

Depression is a major public health concern in modern society, yet little is known about the molecular link between this condition and neuroinflammation. The inflammasome complex was recently shown to be implicated in depression. The present study shows the implication of NLRP3 inflammasome in animal model of stress-induced depression. Accordingly, we show here that in the absence of a NLRP3 inflammasome, prolonged stress does not provoke depressive behaviors or microglial activation in mice or dampen hippocampal neurogenesis. Indeed, NLRP3 deletion or inhibition of microglial activation impairs the stress-induced alterations associated with depression. According to these findings in animal model, the inflammasome could be a target for new therapeutic interventions to prevent depression in patients.

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Acknowledgments

We thank Dr. M. Sefton for editorial assistance. This work has been supported by Grupo de Investigacion Junta de Andalucia CTS113, Consejería de Salud of the Junta de Andalucia (PI-0036-2014), Fundación Ramón Areces, and the Departamento Gobernamental de Investigaciones Científicas y Tecnológicas (DGICYT: BFU2008-01,552 and BFU2011-27,207).

Conflict of Interest

The authors declared that they have no competing interests.

Author information

Authors and Affiliations

  1. Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC-Junta de Andalucía and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, 41013, Sevilla, Spain

    Elísabet Alcocer-Gómez & José Antonio Sánchez-Alcazar

  2. Departamento de Fisiología, Anatomía y Biología Celular, Universidad Pablo de Olavide de Sevilla, Carretera de Utrera Km. 1, 41013, Sevilla, Spain

    Cristina Ulecia-Morón, Tatyana Rybkina & Angel M. Carrión

  3. Research Laboratory, Dental School, University of Sevilla, Sevilla, Spain

    Fabiola Marín-Aguilar, Pedro Bullón & Mario D. Cordero

  4. Dpto. Psiquiatría, Hospital Universitario Virgen Macarena, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain

    Nieves Casas-Barquero

  5. CIBER de Enfermedades Respiratorias, Madrid, Spain; Advanced Imaging Unit, Centro Nacional de Investigaciones Cardiovasculares and Universidad Complutense Madrid, Madrid, Spain

    Jesús Ruiz-Cabello

  6. CNRS, UMR7355, Orléans, France

    Bernhard Ryffel

  7. INSERM, UMR866, Dijon, France

    Lionel Apetoh & François Ghiringhelli

  8. Centre Georges François Leclerc, Dijon, France

    Lionel Apetoh & François Ghiringhelli

  9. Université de Bourgogne, Dijon, France

    Lionel Apetoh & François Ghiringhelli

  10. IBiS Institute of Biomedicine of Seville, University Hospital Virgen del Rocío-CSIC-University of Seville Spain, Sevilla, Spain

    Mario D. Cordero

  11. IBiS Institute of Biomedicine of Seville, Universidad de Sevilla, C/Calle Antonio Maura Montaner s/n, 41013, Sevilla, Spain

    Mario D. Cordero

Authors
  1. Elísabet Alcocer-Gómez
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  2. Cristina Ulecia-Morón
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  3. Fabiola Marín-Aguilar
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  4. Tatyana Rybkina
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  5. Nieves Casas-Barquero
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  6. Jesús Ruiz-Cabello
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  7. Bernhard Ryffel
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  8. Lionel Apetoh
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  9. François Ghiringhelli
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  10. Pedro Bullón
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  11. José Antonio Sánchez-Alcazar
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  12. Angel M. Carrión
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  13. Mario D. Cordero
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Corresponding authors

Correspondence to Angel M. Carrión or Mario D. Cordero.

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Alcocer-Gómez, E., Ulecia-Morón, C., Marín-Aguilar, F. et al. Stress-Induced Depressive Behaviors Require a Functional NLRP3 Inflammasome. Mol Neurobiol 53, 4874–4882 (2016). https://doi.org/10.1007/s12035-015-9408-7

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  • DOI: https://doi.org/10.1007/s12035-015-9408-7

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