Abstract
Oxidative stress and inflammatory cytokines affect the human brain, increasing the risk for mood and cognitive disorders. Such risk might be selective to brain-specific regions. Here, we determined whether BXD recombinant inbred (RI) mice strains are more suitable than C57BL/6J mice for the understanding of the relationship between antioxidant response and inflammatory responses. We hypothesized that inflammatory responses could be independent of antioxidant response and be inherent to brain-specific regions. This hypothesis will be addressed by the analyses of mRNA expression. We explored, at 7-months-of-age, the innate activation of proinflammatory cytokines (tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6), as well as Kelch-like ECH-associating protein 1 (Keap1), nuclear factor erythroid 2 related factor 2 (Nrf2) and glutathione peroxidase 1 (Gpx1) mRNA in both male and female BXD84/RwwJ RI, BXD21/TyJ RI and control strain (C57BL/6J mice). We report that: (1) The cerebellum is more sensitive to antioxidant response in the BXD21/TyJ RI strain; (2) The cerebellum, hippocampus and striatum show increased levels of cytokines in the BXD21/TyJ RI strain; (3) The BXD RI strain has lower brain weight relative to control strain (C57BL/6 mice). In conclusion, our novel data show the utility of the BXD21/TyJ RI strain mice in offering mechanistic insight into Nrf2’s role in the inflammatory system.
Highlights
Oxidative stress and inflammatory cytokines affect the human brain, increasing the risk for mood and cognitive disorders
analysis of variance (ANOVA) revealed no statistically significant differences in body weights between BXD84/RwwJ RI mice and BXD21/TyJ RI compared to controls mice at 7-months-of-age (Fig. 1A)
The brain weights in BXD84/RwwJ (p = 0.000) and RI BXD21/ TyJ RI (p = 0.000) mice were lower compared to controls mice (F(2, 30) = 30.054; p = 0.000)
Summary
Oxidative stress and inflammatory cytokines affect the human brain, increasing the risk for mood and cognitive disorders. Nrf[2] dissociates from Kelch-like ECH-associating protein 1 (Keap1), and translocates into the nucleus where it binds to the antioxidant response element (ARE), and initiates antioxidant gene transcription restoring cellular redox homeostasis[12,13,14,15]. Activation of these transcription factors can lead to the expression of different genes, including those for inflammatory cytokines and anti-inflammatory molecules[8]. If the inflammation persists for a longer time, the second stage of inflammation, or chronic inflammation, sets in predisposing the host to various chronic illnesses[8,19]
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