Figure 1

Perampanel administration for 14 days prevented the death of motor neurons and normalized TDP-43 subcellular localization in AR2H (heterozygous) and AR2 (homozygous) mice.

(a) Number of TO-PRO-3-positive anterior horn cells in the spinal cord (AHCs; ≥20 μm in diameter). Data for the WT, AR2H and AR2 groups are indicated in different colors (white, red and blue, respectively) and the vehicle groups (V; methyl cellulose) are represented as hatched columns in the corresponding colors. NT, no treatment. *p < 0.05 and ***p < 0.0001 against the AR2H-V group; ^#p < 0.05 against the AR2H-V group; and ^‡p < 0.0001 against the WT group. ns, not statistically significant. (b) Number of TDP-43-positive (black columns) and TDP-43-negative (white columns) AHCs. Hatched columns indicate the results on vehicle-treated mice. *p < 0.05, **p < 0.001 and ***p < 0.0001 against the AR2H-V group; and ^#p < 0.05 against the AR2-V group. (c) Representative AHCs with different TDP-43 subcellular localization patterns: predominantly nuclear (N), nucleo-cytoplasmic (N/C) or cytoplasmic (C). The vertical axis indicates the intensity (gray value) evaluated with ImageJ. The threshold for TDP-43 positivity was set at a level 3-fold higher (60 gray) than the background intensity (20 gray). (d) The numbers of AHCs with different subcellular TDP-43 localization patterns are indicated. Hatched columns indicate the results on vehicle-treated mice. ***p < 0.0001 against the AR2H-V with N/C group; ^†p < 0.05 and ^‡p < 0.0001 against the AR2H-V with C group; and ^#p < 0.05 against the AR2-V with C group, Wilcoxon rank sum test. (a,b,d) Data are presented as the mean ± s.e.m. Statistics were based on one-way ANOVA and Tukey post hoc tests unless indicated otherwise. In the WT group, 5 (NT) and 3 (V) mice were included; in the AR2H group, 7 (V), 5 (3.3 mg/kg/day), 8 (6.6), 5 (13.2) and 6 (20) mice were included; and in the AR2 group, 5 in both the V and 13.2 mg/kg/day groups were included.