Fig. 6
From: ACSS2-dependent histone acetylation improves cognition in mouse model of Alzheimer’s disease
The improved synaptic plasticity and cognitive function by the supplementation of ACSS2 substrate via the histone acetylation-mediated upregulation of glutamate receptors in middle-aged 5 × FAD mice. A Representative immunoblots and quantitative analyses of ACSS2, ac-H3K9/H3, and ac-H4K12/H4 in the hippocampus. n = 6 per group. B Relative level of acetyl CoA in the hippocampal lysates of the WT-Veh, WT-GTA, FAD-Veh, and FAD-GTA mice. n = 6 per group. C, D The mRNA levels of genes encoding NMDA receptors (Grin1, Grin2a, Grin2b) and AMPA receptors (Gria1, Gria2, Gria3) in the hippocampi of the WT-Veh, FAD-Veh, and FAD-GTA mice (C). n = 5 per group. Representative immunoblots and quantitative analyses of NMDA receptors (GluN2A, GluN2B) and AMPA receptors (GluA1) in the hippocampus (D). n = 6 per group. E ChIP-qPCR analyses of the enrichment of ac-H4K12 and ac-H3K9 at Grin1, Grin2a, Grin2b, Gria1, Gria2, and Gria3 promoters in the dorsal hippocampi of the FAD-Veh and FAD-GTA mice. Rabbit IgG was used as a negative control. The bars on the top represented the location of primers for detecting ac-H4K12 and ac-H3K9 occupancy. TSS, transcriptional start site. n = 5 per group. F Hippocampal CA1 LTP recordings from the WT-Veh, FAD-Veh, and FAD-GTA mice. Representative fEPSPs showed superimposed traces recorded during baseline and 60 min post-HFS in the hippocampal CA1 area (F, left panel). HFS, high-frequency stimulation. fEPSP amplitude quantification during the last 10 min of LTP recording (F, right panel). n = 7 slices per group. G-J GTA-treated 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 (G). The number of platform-position crossings (H), the percentage of time spent in the target quadrant (I), and the speed (J) in the probe (6d) trial. n = 16, 14, 15, and 15 mice for WT-Veh, WT-GTA, FAD-Veh, and FAD-GTA, respectively. Data are expressed as mean ± SEM. Statistical significance was calculated by three-way ANOVA (G), two-way ANOVA (A, B), one-way ANOVA (C, D, F) followed by the Tukey’s post-test, Scheirer-Ray-Hare test followed by the Dunn’s post-hot test (H-J), and unpaired two-tailed t-test (E). * P < 0.05, ** P < 0.01, *** P < 0.001