Fig. 7 | Signal Transduction and Targeted Therapy

Fig. 7

From: A novel missense variant in ACAA1 contributes to early-onset Alzheimer’s disease, impairs lysosomal function, and facilitates amyloid-β pathology and cognitive decline

Fig. 7

ACAA1 p.N299S disturbs its physiological regulation of excitatory synaptic transmission. a–d Rat hippocampal slice cultures were biolistically transfected with expression vector of ACAA1 WT or ACAA1 p.N299S. Simultaneous dual whole-cell recordings were performed in a transfected CA1 pyramidal neuron (green trace) and a neighboring wild-type one (black trace). The evoked AMPA (a, b) and NMDA (c, d) EPSCs were measured, and open and filled circles represent amplitudes for single pairs and mean ± SEM, respectively. Sample current traces from control (black) and experimental (green) cells are shown as insets. Bar graphs show normalized EPSC amplitudes (mean ± SEM) of −70 mV (a, ***P < 0.001; b, P > 0.05) and +40 mV (c, **P < 0.005; d, P > 0.05) presented in scatter plots. The scale bars for representative EPSC traces are 100 pA/25 ms (a) and 50 pA/25 ms (b–d). e, f Difference of AMPA/NMDA ratios recorded from neurons overexpressing ACAA1 WT (*P < 0.05) or ACAA1 p.N299S (P > 0.05) compared to the respective wild-type (Control) ones. g, h No change in paired-pulse ratio of the second EPSC over the first EPSC from neurons overexpressing ACAA1 WT (P > 0.05) or ACAA1 p.N299S (P > 0.05) relative to the control neurons. All the statistical differences are estimated relative to the respective control neurons, with a two-tailed Wilcoxon signed-rank sum test

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