Fig. 8

α7 nAchR activation reduced NF-κB luciferase signal and downregulated pro-inflammatory genes downstream of NF-κB signaling pathway in brain. a Representative images of NF-κB-dependent luminescence in one hemisphere of the brains (n = 5 mice per group) acquired on the IVIS Spectrum instrument (Perkin Elmer, Hopkinton, MA), using the Perkin Elmer proprietary software, Living Image (v4.3.1). Luciferin was injected intraperitoneally at 150 mg/kg for ex vivo brain imaging, which was conducted after euthanizing the animal and harvesting the brain. b NF-κB-dependent luminescence in the brains of NF-κB luciferase reporter mice was measured by imaging. A significant increase in NF-κB luciferase signal was observed with LPS (1.7 mg/kg) treatment, which was reduced in the presence of GTS21 (25 mg/kg) treatment. *p < 0.05 compared with LPS treated (one-way ANOVA with adjustment for multiple comparisons using Dunnett’s test). Error bars represent SD for n = 10 mice/group from two independent experiments. c RNA analysis of the other brain hemisphere from NF-κB luciferase reporter mice treated with LPS demonstrated statistically significant reductions in gene expression of inflammatory cytokines, TNF-α and IL-6 with 5 mg/kg and 25 mg/kg GTS21 treatment and IL-1β with 25 mg/kg GTS21 treatment, *p < 0.05 compared with LPS treatment (one-way ANOVA with adjustment for multiple comparisons using Dunnett’s test). Error bars represent SD for n = 5 mice/group. d Expression of OSGIN1 and HO1, which are downstream antioxidant genes of Nrf2 pathway, was significantly increased with GTS21 treatment, *p < 0.05 compared with PBS treatment (one-way ANOVA with adjustment for multiple comparisons using Dunnett’s test). Error bars represent SD for n = 5 mice/group