Table 1.
Performed individual tasks, their estimated affected brain regions, and related behavioral abnormalities.
Figure 1.
Open field test in 13-week-old mice.
Total distance traveled (A), vertical activity (B), center time (C), stereotypic counts (D). Tauopathy model mice traveled longer distance (F(1, 33) = 4.467, p = 0.0422, between groups, interaction between genotypes and time; F(1,23) = 1.955, p = 0.0049), showed more vertical activity in the latter half of the task (F(1, 33) = 4.382, p = 0.0441, between groups), spent more time in the center of the field (F(1, 33) = 4.239, p = 0.0475, between groups), significantly. No statistical significance was observed in stereotypic counts (F(1, 33) = 2.226, p = 0.1452, between groups). Controls: wild type mice (n = 19); Mutants: tauopathy model mice (n = 16). Tested with two-way mixed model ANOVA.
Figure 2.
Number of total entries (A), percentage of entries into open arms (B), total distance traveled during the test (C), percentage of time on open arms (D). Percentages of entries into open arms and of time in open arms were significantly increased in tauopathy model mice, respectively. Three wild type mice and 2 tauopathy model mice dropped from the open arms and failed to complete the task. Controls: wild type mice (n = 16); Mutants: tauopathy model mice (n = 15). Tested with Student's t-test.
Figure 3.
Percentage of each minute immobilized (A), distance traveled during the test (B). In the 6th block of Day 1, immobility was decreased (two-way mixed model ANOVA, F(1, 33) = 6.607, p = 0.0149) and distance traveled was increased in tauopathy model mice (two-way mixed model ANOVA, F(1, 33) = 7.308, p = 0.0108). In general, no statistical significance was observed, tested with two-way mixed model ANOVA (immobility: Day 1, F(1, 33) = 3.958, p = 0.055, between groups. Day 2, F(1, 33) = 2.246, p = 0.1434, between groups; distance traveled: Day 1, F(1, 33) = 0.324, p = 0.5733, between groups. Day 2, F(1, 33) = 0.915, p = 0.3458, between groups). Controls: wild type mice (n = 19); Mutants: tauopathy model mice (n = 16).
Figure 4.
Startle amplitude (A), percentage of prepulse inhibition (B). Tauopathy model mice had lower startle amplitudes than wild type mice at both 110 dB and 120 dB, statistically significant at 120 dB. Percent PPI was significantly greater in tauopathy model mice. Controls: wild type mice (n = 19); Mutants: tauopathy model mice (n = 16). Tested with Mann-Whitney's U-test in startle amplitude 110 dB, the others with Student's t-test.
Figure 5.
Number of total entries (A), number of total alternations (B), total distance traveled (C), percentage of alternations (D). In tauopathy model mice, significantly increased numbers of total entries and total alternations, and prolonged distance traveled were observed. Percentage of alternations was significantly decreased, suggesting that short-term memory was impaired in tauopathy model mice. Controls: wild type mice (n = 19); Mutants: tauopathy model mice (n = 16). Tested with Mann-Whitney's U-test in % alternation, the others with Student's t-test.
Figure 6.
Crawley's social interaction test.
The 1st trial with one-stranger mouse (A–D, I, J), the 2nd trial with one-familiar mouse and one-stranger mouse (E–H, K, L). Time spent in each chamber was tested with one-way ANOVA, followed by Fisher's least significant difference method as post hoc analysis within groups, with Student's t-test between groups. Time spent in each cage (mouse with no prior contact with a subject mouse) was analyzed by Student's t-test and Welch's t-test. In the 1st trial, both groups spent more time in the chamber (A, B) and the cage (C, D) of the stranger side. In the 2nd trial, no statistical significance was observed between the time spent in the stranger and familiar chambers of the two groups (Controls: p = 0.7166; Mutants: p = 0.2116, Controls vs Mutants: Stranger side: p = 0.5308, Empty side: p = 0.4412). Control wild type mice showed significantly more time spent with stranger mice (G, Controls vs Mutants: p = 0.03761 (Welch's t-test), Familiar side: p = 0.04053 (Student's t-test)). However, tauopathy model mice tended to spend more time with familiar mice (H). Controls: wild type mice (n = 19); Mutants: tauopathy model mice (n = 16).
Figure 7.
Training session (A, B), probe test 24 h after the last (6th) training (C–G). No statistical significances were observed in the training session with the visible platform (A, F(1,46) = 0.0395, p = 0.8434, between groups), but tauopathy model mice spent significantly more time to find the invisible platform (B, F(1,46) = 11.2326, p = 0.0016, between groups). Tested by two-way mixed model ANOVA. In the probe trial, tauopathy model mice showed less time (C, p<0.0001) and path length (D, p<0.0001) in the pool quadrant where the platform had previously been placed, and smaller numbers of target platform crossings (E, p<0.0001). No statistical significance was observed in total path length (F, p>0.05) and swimming speed (G, p>0.05) between the two groups of mice. Controls: wild type mice (n = 11); Mutants: tauopathy model mice (n = 29). Tested with Student's t-test.
Figure 8.
Percentage of freezing time of each minute of conditioning (A), context testing (B), cued testing with altered context (C). Freezing tended to be reduced in tauopathy model mice in context testing. In the 4th block, freezing was significantly decreased (two-way mixed model ANOVA, F(1, 33) = 5.479, p = 0.0254). In general, no statistical significance was observed as tested with two-way mixed model ANOVA (Conditioning: F(1, 33) = 0.006, p = 0.9378, between groups; Context testing: F(1, 33) = 3.000, p = 0.0926, between groups; Cued testing: F(1, 33) = 0.771, p = 0.3863, between groups). Controls: wild type mice (n = 19); Mutants: tauopathy model mice (n = 16).
Figure 9.
Representative immunofluorescence histological findings of tauopathy model mice and wild type mice.
Male mice 4 months of age: Tauopathy model mice (A–D), and wild type mice (E–H). Lateral globus pallidus (A, E), anterior cortical amygdaloid nucleus (B, F), auditory cortex (C, G), and ventral hippocampus (CA3; D, H). Scale Bar: 100 µm.
Figure 10.
Representative immunoblotting of the whole cortex (A) and the whole hippocampus (B) of mice at the age of 6 months, after the comprehensive behavioral analysis.
Phosphorylated tau was observed in the brains of tauopathy model mice, both in the cortex and in the hippocampus, but not in those of control mice. Each 5 samples were randomly selected.