Fig. 8: Chronic memantine treatment improves the neurodevelopmental and behavioral deficits of Xpnpep1–/– mice. | Experimental & Molecular Medicine

Fig. 8: Chronic memantine treatment improves the neurodevelopmental and behavioral deficits of Xpnpep1–/– mice.

From: Suppression of exaggerated NMDAR activity by memantine treatment ameliorates neurological and behavioral deficits in aminopeptidase P1-deficient mice

Fig. 8

a Rescue of developmental delay by memantine. Representative image of male mice at 5 weeks old. b Weight curves of male mice. n = 33 (+/+, sal), 20 (+/+, mem), 26 (–/–, sal), and 14 (–/–, mem) mice. Genotype, F(1, 89) = 471.29, p = 0; treatment, F(1, 89) = 61.24, p < 0.001; interaction, F(1, 89) = 56.83, p < 0.001; at 5 weeks old. c Averaged body lengths of male mice at 5 weeks old in each group are summarized. n = 7 (+/+, Sal), 8 (+/+, Mem), 6 (–/–, Sal), and 6 (–/–, Mem) mice. Genotype, F(1, 23) = 28.10, p < 0.001; treatment, F(1, 23) = 17.52, p < 0.001; interaction, F(1, 23) = 32.26, p < 0.001. d Open-field activities of mice in each group with 5-min intervals. n = 16 (+/+, sal; black circles), 12 (+/+, mem; gray triangles), 16 (–/–, sal; red circles), and 11 (–/–, mem; blue squares) mice. e Quantification of activity during the entire 1-h period in the open field test. Genotype, F(1, 51) = 99.346, p < 0.001; treatment, F(1, 51) = 23.427, p < 0.001; interaction, F(1, 51) = 13.175, p < 0.001. f Plots of open-field activity against body weight show a strong correlation between hyperactivity and developmental delay. “R” represents the Pearson’s correlation coefficient. g–j Chronic memantine treatment improved hippocampus-dependent learning and memory in Xpnpep1–/– mice. The preference for a new object (g) and total exploration time (h) in the NOR test. n = 11 (+/+, sal), 7 (+/+, mem), 8 (–/–, sal), and 10 (–/–, mem) mice. g Genotype, F(1, 32) = 12.20, p = 0.0014; treatment, F(1, 32) = 13.25, p < 0.001; interaction, F(1, 32) = 7.82, p = 0.0086. h Genotype, F(1, 32) = 2.81, p = 0.103; treatment, F(1, 32) = 3.496, p = 0.070; interaction, F(1, 32) = 0.167, p = 0.685. i Quantification of locomotor activity during contextual fear conditioning tests. n = 13 (+/+, sal), 10 (+/+, mem), 8 (–/–, sal), and 10 (–/–, mem) mice. ###p < 0.001; ns, not significant (p ≥ 0.05) by Mann–Whitney tests. U = 0 and Z = –4.33 (+/+, sal); U = 0 and Z = –3.78 (+/+, mem); U = 20 and Z = –1.26 (–/–, sal); U = 1 and Z = –3.70 (–/–, mem). Distance moved during CS; genotype, F(1, 37) = 85.274, p < 0.001; treatment, F(1, 37) = 6.867, p = 0.012; interaction, F(1, 37) = 10.33, p = 0.0027. j Extent of activity suppression in each group is summarized. Genotype, F(1, 37) = 51.81, p < 0.001; treatment, F(1, 37) = 4.476, p = 0.041; interaction, F(1, 37) = 7.019, p = 0.011. b, c, e, g–j *p < 0.05; **p < 0.01; ***p < 0.001; n.s., not significant (p ≥ 0.05); two-way ANOVA with the Tukey multiple comparison test. k Slopes of fEPSPs measured at the hippocampal SC-CA1 synapse from WT and Xpnpep1–/– mice that underwent chronic memantine treatment are plotted against time as a percentage of baseline. n = 9 slices from three mice of each genotype. (inset) Sample traces of fEPSPs obtained at the indicated time points (1 and 2); Scale bars, 5 ms and 0.5 mV. l Magnitudes of LTP measured during the last 5 min of recording are summarized. t(16) = −0.754 and p = 0.461 by Student’s t test.

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