title: Nrf2 participates in depressive disorders through an anti-inflammatory mechanism.
abstract: 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.
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain; Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Martín-de-Saavedra
authors.forename: Josiane
authors.initials: J
authors.lastname: Budni
authors.forename: Mauricio P
authors.initials: MP
authors.lastname: Cunha
authors.forename: Vanessa
authors.initials: V
authors.lastname: Gómez-Rangel
authors.forename: Silvia
authors.initials: S
authors.lastname: Lorrio
authors.forename: Laura
authors.initials: L
authors.lastname: Del Barrio
authors.forename: Isabel
authors.initials: I
authors.lastname: Lastres-Becker
authors.forename: Esther
authors.initials: E
authors.lastname: Parada
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Tordera
authors.forename: Ana Lùcia S
authors.initials: AL
authors.lastname: Rodrigues
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuadrado
authors.forename: Manuela G
authors.initials: MG
authors.lastname: López
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology; D003866:Depressive Disorder / Q000097:blood / Q000235:genetics*; D004298:Dopamine / Q000097:blood; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D009473:Neuronal Plasticity / Q000235:genetics; D012701:Serotonin / Q000097:blood; D015398:Signal Transduction / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D012701:Serotonin; D004298:Dopamine
keywords: Depression; Inflammation; Nrf2; Rofecoxib; Sulforaphane; Trophic factors