Fig. 3: Host- and microbiota-derived AHR ligands have opposing effects on MG survival after oxygen-glucose deprivation and reperfusion (OGD/R). | Nature Communications

Fig. 3: Host- and microbiota-derived AHR ligands have opposing effects on MG survival after oxygen-glucose deprivation and reperfusion (OGD/R).

From: Benefits of equilibrium between microbiota- and host-derived ligands of the aryl hydrocarbon receptor after stroke in aged male mice

Fig. 3

a Schematic showing sorted MG cells from naive aged WT mice treated with indole-based AHR ligands (indole-3-carboxaldehyde and indole-3-propionate) ex vivo. The cells received OGD/R to model stroke conditions. b MG AHR expression and MG survival post-OGD/R differ based on the AHR ligands present. AHR expression was increased after OGD/R and depleting tryptophan (Trp) from OGD/R media reversed this effect (n = 4/group for Vehicle, OGD, Trp Dep OGD (p < 0.0100), and Trp Dep Kyn OGD (p < 0.0001) and n = 8 for Trp Dep Indoles OGD (p < 0.0001) group). The addition of Kynurenine (Kyn) or indole-based AHR ligands (indole-3-carboxaldehyde and indole-3-propionate) led to an increase in AHR expression post-OGD/R. MG survival after OGD/R was significantly lower when Kyn was present relative to when Trp was depleted. Post-OGD/R MG survival increased when indole-based ligands were added (n = 4/group for Vehicle, OGD, Trp Dep OGD, and Trp Dep Kyn OGD and n = 8 for Trp Dep Indoles OGD group). c Schematic showing treatment of mice with indoles (indole-3-carboxaldehyde and indole-3-propionate) in vivo via oral gavage. MG were sorted from indole-treated mice and received OGD/R. d MG survival was increased post-OGD/R in the group treated with indoles relative to the vehicle group (n = 5/grp, p = 0.0249). e Kyn-mediated activation of AHR was detrimental, whereas indole-mediated activation of AHR did not worsen MG survival after OGD/R (n = 6/grp, p = 0.0256). f qPCR-based examination showed that the expression levels of IL-1b, IL−4, and IL-10 are significantly reduced in indole-treated relative to the Kyn-treated group (n = 6/grp, p < 0.0001 for all for all three comparisons). The schematic figures were created in BioRender. Unpaired two-tailed t-test (d) and Tukey’s two-way ANOVA with multiple comparisons (b, e, f) were used for statistical analyses. All data (with error bars) are presented as mean ± SEM. All data points presented are biological replicates.

Back to article page