Fig. 7
From: ACSS2-dependent histone acetylation improves cognition in mouse model of Alzheimer’s disease
The prevention of acetate supplementation-induced upregulation of glutamate receptors and cognitive improvement by Acss2 knockdown in middle-aged 5 × FAD mice. A The time schedule for the GTA treatment on the premise of Acss2 knockdown in the dorsal hippocampus. B-E Mice were tested in the Morris water maze. Escape latency to the platform position during the training trails (1-5d) and the probe (6d) trial (B). The number of platform-position crossings (C), the percentage of time spent in the target quadrant (D), and the speed (E) in the probe (6d) trial. n = 11, 14, and 13 mice for FAD-GFP-Veh, FAD-GFP-GTA, and FAD-shAcss2-GTA, respectively. F Relative level of acetyl CoA in the dorsal hippocampi of the FAD-GFP-Veh, FAD-GFP-GTA, FAD-shAcss2-GTA mice. n = 6 per group. G Representative immunoblots and quantitative analyses of ACSS2, ac-H3K9/H3, and ac-H4K12/H4 in the dorsal hippocampus. n = 6 per group. H, I The mRNA levels of genes encoding NMDA receptors (Grin1, Grin2a, Grin2b) (H, left panel) and AMPA receptors (Gria1, Gria2, Gria3) (H, right panel) in the dorsal hippocampus of the FAD-GFP-Veh, FAD-GFP-GTA, FAD-shAcss2-GTA mice. n = 6 per group. Representative immunoblots and quantitative analyses of GluN2A and GluA1 in the dorsal hippocampus (I). n = 6 per group. J A proposed working model of acetate supplementation for inducing upregulation of glutamate receptors and cognitive improvement in middle-aged 5 × FAD mice, which was prevented by Acss2 knockdown. Data are expressed as mean ± SEM. Statistical significance was calculated by two-way ANOVA (B) and one-way ANOVA (C-I) followed by the Tukey’s post-test. * P < 0.05, ** P < 0.01, *** P < 0.001