1. Fig. 4. Perampanel ameliorates behavioral deficits in mice expressing the Thorase variants.
Perampanel ameliorates behavioral deficits in mice expressing the Thorase variants. (A to D) Open-field test assessments in WT mice (brown) and heterozygous Thorase-deficient mice expressing WT Thorase (Het-WT; black) or the Thorase variants R9H (orange), D221H (blue), and E290K (green). (A) Representative pathview images of the open-field activities of the mice treated with vehicle, the psychostimulant MK-801, or Perampanel showing characteristics of the patterns of locomotor activity. (B) Graphical representation of the total distance traveled by mice in the open-field test after treatment with vehicle or MK-801. (C) Graphical representation of the total distance traveled by mice in the open-field test after treatment with vehicle or Perampanel. Means ± SEM (n = 10). ***P < 0.01; **P < 0.05; *P < 0.1; n.s., P > 0.10, ANOVA with Holm-Sidak post hoc test when compared to Het-WT (black). Power (1 − β error probability) = 0.8 to 1.0. (D) Percent central and peripheral activities in the open-field test after treatment with vehicle or Perampanel. (E) Graphical representation of percent correct spontaneous alternation in the Y-maze spatial working memory test after treatment with vehicle or Perampanel. (F) Prepulse inhibition (PPI) in the acoustic startle response test. The graphs represent the percent PPI at different prepulse intensities after treatment with vehicle or Perampanel. Means ± SEM (n = 7 to 10). ***P < 0.01; **P < 0.05; *P < 0.1; n.s., P > 0.10, ANOVA with Holm-Sidak post hoc test when compared to Het-WT (black). Power (1 − β error probability) = 0.9 to 1.0. (G) Assessment of social interactions by WT mice (brown), heterozygous Thorase-deficient mice expressing WT Thorase (Het-WT; black), or the Thorase variants R9H (orange), D221H (blue), and E290K (green). Graph represents number of mouse visits to a chamber containing a new unfamiliar mouse versus an empty chamber. (H) Evaluation of social memory in WT mice (brown), heterozygous Thorase-deficient mice expressing WT Thorase (Het-WT; black), or the Thorase variants R9H (orange), D221H (blue), and E290K (green). Graph represents number of mouse visits to a chamber containing either a familiar mouse or a new unfamiliar mouse. (I and J) Trace fear conditioning to assess contextual memory and associative learning in WT mice (brown), heterozygous Thorase-deficient mice expressing WT Thorase (Het-WT; black), or the Thorase variants R9H (orange), D221H (blue), and E290K (green). (I) Mean percent freezing by mice during the test to assess contextual memory. (J) Mean percent freezing by mice during the cue test. Graphical representation of the average freezing time for the first two audible tones is shown. Means ± SEM (n = 12). ***P < 0.005; **P < 0.01; *P < 0.05, two-way ANOVA with Tukey-Kramer post hoc test compared to Het-WT (black). Power (1 − β error probability) = 1.0.
George K. E. Umanah et al., Sci Transl Med 2017;9:eaah4985
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