TY - JOUR
T1 - The BXD21/TyJ recombinant inbred strain as a model for innate inflammatory response in distinct brain regions
AU - López-Granero, Caridad
AU - Ferrer, Beatriz
AU - dos Santos, Alessandra Antunes
AU - Barrasa, Angel
AU - Aschner, Michael
N1 - Funding Information:
The authors would like to thank Frances Manon for her excellent assistance. MA was supported in part by NIH grants from the National Institute of Environmental Health Sciences, R01 ES10563, R01 ES07331 and R01 ES020852. Additional support was obtained from Gobierno de Aragón (S24_17R) (Spain) and FEDER founds 2014–2020 "Construyendo Europa desde Aragón" (European Union) and Fundación IBERCAJA (Spain).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-020-70213-9
DO - 10.1038/s41598-020-70213-9
M3 - Article
C2 - 32759955
AN - SCOPUS:85089012653
VL - 10
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 13168
ER -