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. 2020 Dec 9;108(5):887–904.e12. doi: 10.1016/j.neuron.2020.09.010

Figure 4.

Figure 4

APAP Treatment Rescues Microglial Morphology and Activity, Dendritic Spine Deficits, and Cognitive Impairment in Dp(16) Mice

(A) Experimental protocol.

(B) Iba1-stained hippocampal slices from WT and Dp(16) animals treated with either vehicle or APAP. Scale bar: 10 μm.

(C) Quantification of the cell body area of microglial cells. Bars represent the average of microglial cell body areas in all analyzed animals ± SEM, and circles represent single data points of the cell averages for each animal (14–73 cells/animal; 1 slice per animal). ∗p < 0.05; two-way ANOVA; FInteraction (1, 23) = 14.88; p = 0.0008; Holm-Sidak post hoc test. Dotted circles represent data are from Figure 1C for comparison.

(D) Voltage-activated current profile of microglia in WTCX3CR1-GFP and Dp(16)CX3CR1-GFP acute hippocampal slices treated with vehicle or APAP in vivo. Voltage currents were analyzed using ramps ranging from −100 to 80 mV (inset). Data are expressed as average current (picoAmpere,pA) normalized for the capacitance (picoFarad,pF) for each mV step of all analyzed cells ± SEM. ∗ represents the statistical difference between Dp(16) and WT vehicle; ∗∗p < 0.01; ∗∗∗p < 0.001; § represents the statistical difference between Dp(16) vehicle and Dp(16) APAP; §§p < 0.01; §§§p < 0.001. Two-way RM ANOVA; FInteraction (27, 1,890) = 9.261; p < 0.001; Holm-Sidak post hoc test. In parenthesis: analyzed cells, animals. The vehicle-treated data are from Figure 1I for comparison.

(E) Dendritic spines from Golgi-Cox-stained slices of hippocampi from P22 WT and Dp(16) mice treated with vehicle or APAP. Scale bar: 4 μm.

(F) Quantification of the spine density. Bars represent the average spine density of all analyzed cells ± SEM, and circles represent single data points for each cell (3 animals per condition). ∗∗∗p < 0.001; two-way ANOVA; FInteraction (1, 56) = 42.99; p < 0.001; Holm-Sidak post hoc test. The vehicle-treated cell data (dotted circles) are from Figure 3C for comparison.

(G and H) Quantification of the discrimination index in the NOR and OLT tests in P22 WT and Dp(16) mice following vehicle or APAP treatment. Bars represent the average discrimination index of all analyzed animals ± SEM, and symbols (circles, males; triangles, females) represent single data points for each animal. ∗p < 0.05; ∗∗p < 0.01; (G) two-way ANOVA, FInteraction (1, 51) = 23.76, p < 0.001; Holm-Sidak post hoc test; (H) two-way ANOVA, FInteraction (1, 35) = 11.24, p < 0.002; Holm-Sidak post hoc test. The vehicle-treated data (dotted circles and triangles) are from Figures 2E or 2F for comparison.