Nrf2 participates in depressive disorders through an anti-inflammatory mechanism

PSYCHONEUROENDOCRINOLOGY

卷:38

Article

Dolores Martin-de-Saavedra, Maria^1,2  Budni, Josiane⁴  Cunha, Mauricio P.⁴  Gomez-Rangel, Vanessa^1,2  Lorrio, Silvia^1,2,3  del Barrio, Laura^1,2  Lastres-Becker, Isabel^3,5,6,7  Parada, Esther^1,2  Maria Tordera, Rosa⁸  Rodrigues, Ana Lucia S.⁴  Cuadrado, Antonio^3,5,6,7  Lopez, Manuela G.^1,2 

[1] Univ Autonoma Madrid, Fac Med, Inst Teofilo Hernando, E-28029 Madrid, Spain

[2] Univ Autonoma Madrid, Fac Med, Dept Farmacol & Terapeut, E-28029 Madrid, Spain

[3] Hosp Univ La Paz IdiPaz, Inst Invest Sanitaria, Madrid, Spain

[4] Univ Fed Santa Catarina, Dept Bioquim, Florianopolis, SC, Brazil

[5] Dept Bioquim, Madrid, Spain

[6] Inst Invest Biomed Alberto Sols UAM CSIC, Madrid, Spain

[7] Inst Salud Carlos III, Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Madrid, Spain

[8] Univ Navarra, Dept Farmacol, Navarra, Spain

关键词: Nrf2;    Depression;    Inflammation;    Rofecoxib;    Trophic factors;    Sulforaphane;   

DOI  :  10.1016/j.psyneuen.2013.03.020

来源: Elsevier

【 摘 要 】

A causative relationship between inflammation and depression is gradually gaining consistency. Because Nrf2 participates in inflammation, we hypothesized that Nrf2 could play a role in depressive disorders. In this study, we have observed that Nrf2 deletion in mice results in: (i) a depressive-like behavior evaluated as an increase in the immobility time in the tail-suspension test and by a decrease in the grooming time in the splash test, (ii) reduced levels of dopamine and serotonin and increased levels of glutamate in the prefrontal cortex, (iii) altered levels of proteins associated to depression such as VEGF and synaptophysin and (iv) microgliosis. Furthermore, treatment of Nrf2 knockout mice with the anti-inflammatory drug rofecoxib reversed their depressive-like behavior, while induction of Nrf2 by sulforaphane, in an inflammatory model of depression elicited by LPS, afforded antidepressant-like effects. In conclusion, our results indicate that chronic inflammation due to a deletion of Nrf2 can lead to a depressive-like phenotype while induction of Nrf2 could become a new and interesting target to develop novel antidepressive drugs. (C) 2013 Elsevier Ltd. All rights reserved.

【 授权许可】

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