Fig. 4: A PPARγ antagonist pretreatment prevents CBD-mediated lifespan extension and most disease comorbidities.
From: Cannabidiol ameliorates mitochondrial disease via PPARγ activation in preclinical models
a Kaplan–Meier survival curve of Gad2:Ndufs4cKO mice treated daily with vehicle (n = 24, gray), CBD (n = 18, red), GW9662+Veh (n = 16, blue), GW9662 + CBD (n = 18, green), and control mice (n = 20, black). GW9662 (1 mg/kg) was administered 20 min before each CBD or vehicle injection (Long-rank test, ****p < 0.0001 vs Veh-treated Gad2:Ndufs4cKO mice; ##p = 0.0040 vs CBD-treated Gad2:Ndufs4cKO mice; &p = 0.0112 vs GW9662-Veh-treated Gad2:Ndufs4cKO mice). Survival graphs of Gad2:Ndufs4cKO-Veh (gray) and Gad2:Ndufs4cKO-CBD (red) are also displayed in Fig. 2a. % of time spent in open arms (b), % of entries in open arms (c), and total arm entries (d) in the elevated plus maze of Gad2:Ndufs4cKO and control mice pretreated daily with GW9662 20 min before vehicle (blue, n = 16 [control], 15 [Gad2:Ndufs4cKO]) or CBD (green, n = 11 [control], 18 [Gad2:Ndufs4cKO]) administration (two-way ANOVA followed by Tukey’s multiple comparisons test, ****p < 0.0001 vs Veh-treated control; &&p = 0.0028, &&&p = 0.0002 vs CBD-treated control). Discrimination index of the time exploring a stranger mouse over an empty wire cage (e) and total exploration time (f) in the 3-chamber social interaction test of Gad2:Ndufs4cKO and control mice pretreated daily with GW9662 20 min before vehicle (blue, n = 14 [control], 18 [Gad2:Ndufs4cKO]) or CBD (green, n = 9 [control], 24 [Gad2:Ndufs4cKO]) administration (two-way ANOVA followed by Tukey’s multiple comparisons test, *p = 0.0178, **p = 0.0010 vs Veh-treated control; &p = 0.0322, &&p = 0.0048 vs CBD-treated control). Quantification of IBA1 (g) or GFAP (h) fluorescence signal intensity in the GPe of Gad2:Ndufs4cKO and control mice pretreated daily with GW9662 20 min before vehicle (blue, n = 6 [control], 4 [Gad2:Ndufs4cKO]) or CBD (green, n = 6) administration (one-way ANOVA followed by Tukey’s multiple comparisons test, *p = 0.0404, ***p = 0.0007 vs Veh-treated control; #p < 0.05 vs Veh-treated cKO). All data are presented as mean values ± SEM. All source data are provided as a source data file. Veh vehicle, CT control mice, cKO Gad2:Ndufs4cKO mice.
