Fig. 6

Rebalancing histone acetylation rescues neurogenic deficits in Fmr1 KO mice. a, e Experimental schemes for assessing histone acetylation (a) and NSC activation (e) in WT and Fmr1 KO mice treated with curcumin, Nutlin-3, or vehicle. b Sample confocal images of acetylated histone H3 in the NSCs of 6-month-old WT and Fmr1 KO-Nes-GFP mice. Blue, DAPI; green, GFP; red, acetyl-H3. Scale bar, 20 µm. c, d Curcumin treatment (c, n = 3 mice per group) or Nutlin-3 (d, n = 3 to 4 mice per group) reduced histone H3 acetylation in GFP⁺ NSCs Fmr1 KO mice without affecting WT mice. f Sample confocal images of activated NSCs (GFP⁺GFAP⁺MCM2⁺) in the dentate gyrus of 6-month-old WT or Fmr1 KO (Nes-GFP) mice. Blue, DAPI; green, GFP; red, MCM2. Scale bar, 20 µm. g, h Curcumin (g, n = 3 to 4 mice per group) or Nutlin-3 treatment (h, n = 3 mice per group) rescued NSC activation in Fmr1 KO mice. i Experimental scheme for assessing neuronal differentiation in WT and Fmr1 KO mice treated with curcumin, Nutlin-3, or vehicle. j Sample confocal images of newborn neurons (DAPI⁺NeuN⁺BrdU⁺) in the dentate gyrus of WT and Fmr1 KO mice. Blue, DAPI; green, NeuN; red, BrdU. Scale bar, 20 µm. k, l curcumin (k, n = 4 to 5 mice per group) or Nutlin-3 treatment (l, n = 4 to 5 mice per group) rescued neuronal differentiation specifically in Fmr1 KO mice. *P < 0.05, **P < 0.01, ***P < 0.001, n.s.: no significant difference. Two-way ANOVA was used for all data analyses. Data are presented as mean ± s.e.m. The boxes with dotted white lines in b, f, j indicate regions where higher magnification images are shown