Depression is one of the most common
mood disorders with a high rate of relapse. Accumulating evidence suggests that the
transcription factor Kelch-like erythroid cell-derived
protein with CNC homology (ECH)-associated
protein 1 (Keap1)-Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) system plays a key role in
inflammation which is involved in depression. Preclinical studies demonstrated that the
protein expressions of Keap1 and Nrf2 in the prefrontal cortex (PFC), CA3 and dentate gyrus (DG) of hippocampus in mice with depression-like phenotype were lower than control mice. In the learned helplessness paradigm, the
protein levels of Keap1 and Nrf2 in the PFC and DG of hippocampus from rats with depression-like phenotype were also lower than control and resilient rats. Furthermore, rodents with depression-like phenotype have higher levels of pro-inflammatory
cytokines. Interestingly, Nrf2 knock-out (KO) mice exhibit depression-like phenotype, and higher serum levels of pro-inflammatory
cytokines compared with wild-type mice. Furthermore, Nrf2 KO mice have lower expression of
brain-derived neurotrophic factor (
BDNF) in the PFC, and CA3 and DG of hippocampus compared to wild-type mice.
7,8-Dihydroxyflavone, a TrkB agonist, showed
antidepressant effects in Nrf2 KO mice, by stimulating
BDNF-TrkB in the PFC, CA3, and DG. Pretreatment with
sulforaphane, a naturally occurring Nrf2 activator, prevented depression-like phenotype in mice after
inflammation, or chronic social defeat stress. Interestingly, dietary intake of 0.1%
glucoraphanin (a precursor of
sulforaphane) containing food during juvenile and adolescent stages of mice could prevent depression-like phenotype in adulthood after chronic social defeat stress. Moreover, the
protein expressions of Keap1 and Nrf2 in the parietal cortex from
major depressive disorder and
bipolar disorder were lower than controls. These findings suggest that Keap1-Nrf2 system plays a key role in the stress resilience which is involved in the pathophysiology of
mood disorders. It is, therefore, possible that dietary intake of cruciferous vegetables including
glucoraphanin (or SFN) may prevent or minimize relapse from remission, induced by stress and/or
inflammation in depressed patients. In the review, the author would like to discuss the role of Keap1-Nrf2 system in
mood disorders.