Fig. 8

UNC9995 attenuates apoptosis and inflammation of astrocytes and can be canceled by depletion of β-arrestin2. A Cell viability of astrocytes pretreated with UNC9995 (1, 5, 10, and 20 μM) for 1 h and then stimulated with IL-6 (300 ng/mL) for 24 h in WT and Arrb2^−/− astrocytes. B, C Apoptosis rate was detected by flow cytometry which was pretreated with UNC9995 for 1 h and then stimulated with IL-6 (300 ng/mL) for 24 h in WT and Arrb2^−/− astrocytes. Levels of cytokines TNF-α (D) and IL-1β (E) were detected by ELISA. WT and Arrb2^−/− mice were made CUMS models. The time in the center area (F, G), bouts of food sniff (H), latency to sniff (I), and latency to feed (J) in CUMS model mice were detected. K Immunofluorescence staining GFAP in the hippocampus of WT and Arrb2^−/− mice. L, M Cytokines of IL-1β, TNF-α, and IFN-β in the hippocampus and plasma were detected. N Schmeichel model of activation of β-arrestin2-biased signaling by UNC9995 in the depression mouse model. Data are analyzed using two-way ANOVA, then combined with Tukey to assess the differences between groups. ns, P > 0.05. *P < 0.05, **P < 0.01, ***P < 0.001 VS WT Control group. ^#P < 0.05, ^##P < 0.01, ^###P < 0.001 VS WT IL-6 group or WT CUMS group. ^$P < 0.05, ^$$P < 0.01, ^$$$P < 0.001