Fig. 5
From: ACSS2-dependent histone acetylation improves cognition in mouse model of Alzheimer’s disease
The ACSS2 upregulation-restored synaptic plasticity via the histone acetylation-mediated expression of glutamate receptors in middle-aged 5 × FAD mice. A, B The real-time quantitative PCR (RT-qPCR) analysis of genes encoding NMDA receptors subunits (Grin1, Grin2a, Grin2b) and AMPA receptors subunits (Gria1, Gria2, Gria3) in the dorsal hippocampi of the WT-GFP, WT-ACSS2, FAD-GFP, and FAD-ACSS2 mice (A). n = 5 per group. Representative immunoblots and quantitative analyses of NMDA receptors subunits (GluN2A, GluN2B), AMPA receptors subunits (GluA1), ac-H3K9/H3, and ac-H4K12/H4 in the dorsal hippocampus (B). n = 6 per group. C Relative acetyl-CoA levels in the dorsal hippocampus (n = 6 per group). D 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 WT-GFP, FAD-GFP, and FAD-ACSS2 mice. Rabbit IgG was used as the 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. E Representative traces of mIPSCs. mIPSCs were recorded at a holding potential of 0 mV (scale bar = 100 ms, 10 pA) (E, top panel). Quantitative analysis of the amplitude and frequency of mIPSCs (E, bottom panel). n = 23–24 cells per group. F Representative traces of mEPSCs. mEPSCs were recorded at a holding potential of –70 mV (scale bar = 100 ms, 10 pA) (F, top panel). Quantitative analysis of the amplitude and frequency of mEPSCs (F, bottom panel). n = 20–22 cells per group. G Hippocampal CA1 LTP recordings from the WT-GFP, FAD-GFP, and FAD-ACSS2 mice. Representative fEPSPs showed superimposed traces recorded during baseline and 60 min post-HFS in hippocampal CA1 area (G, top panel). HFS, high-frequency stimulation. fEPSP amplitude quantification during the last 10 min of LTP recording (G, bottom panel). n = 7 slices per group. H A proposed working model by which ACSS2 regulates synaptic plasticity and cognitive function in 5 × FAD mice. Data are expressed as mean ± SEM. Statistical significance was calculated by two-way ANOVA (A-C) and one-way ANOVA (D-G) followed by the Tukey’s post-test. * P < 0.05, ** P < 0.01, *** P < 0.001