Role of Keap1-Nrf2 signaling in depression and dietary intake of glucoraphanin confers stress resilience in mice

• DOI: 10.1038/srep30659
• Publication Date: 2016-07-29T09:10:22Z
• Authors: Wei Yao; Ji-chun Zhang; Tamaki Ishima; Chao Dong; Chun Yang; Qian Ren; Min Ma; Mei Han; Jin Wu; Hiroyuki Suganuma; Yusuke Ushida; Masayuki Yamamoto; Kenji Hashimoto
• Keywords: Mice, Knockout; 0303 health sciences; Kelch-Like ECH-Associated Protein 1; Depression; NF-E2-Related Factor 2; Glucosinolates; Prefrontal Cortex; Hippocampus; Article; Diet; Mice, Inbred C57BL; Disease Models, Animal; 03 medical and health sciences; Neuroprotective Agents; Sulfoxides; Imidoesters; Oximes; Animals; Signal Transduction

Abstract The transcription factor Keap1-Nrf2 system plays a key role in inflammation which is involved depression. We found lower expression of Keap1 and Nrf2 proteins the prefrontal cortex (PFC), CA3 dentate gyrus (DG) hippocampus mice with depression-like phenotype compared to control mice. Serum levels pro-inflammatory cytokines knock-out (KO) were higher than those wild-type mice, suggestive enhanced KO Decreased brain-derived neurotrophic (BDNF) its receptor tropomyosin-receptor-kinase B (TrkB) signaling PFC, DG TrkB agonist 7,8-dihydroxyflavone, but not antagonist ANA-12, produced antidepressant effects by stimulating DG. Pretreatment activator sulforaphane (SFN) prevented induced after repeated social defeat stress. Interestingly, dietary intake 0.1% glucoraphanin (a precursor SFN) containing food during juvenile adolescent stages also evoked adulthood, These findings suggest that depression SFN-rich adolescence can confer stress resilience adulthood.