
Figure 1
Percentile actograms of NoTg and 3xTg-AD mice at 3, 8, and 13 Mo. In each actogram, an arrowhead indicates the advance (to the left), the delay (to the right), and the start of DD (downwards). The lower panel shows the average (±SE) of free-running periods in DD (left) and amplitude (right). NoTg mice in black and 3xTg-AD mice in gray bars (two-way ANOVA with Tukey’s post hoc test, p < 0.05, n = 7–13).

Figure 2
Average steady-state activity profiles per hour (±SE) of the NoTg mice (black lines, n = 26) and 3xTg-AD mice (gray lines, n = 28). Initial (top), 6h Advance (middle) and 6h Delay (bottom). The asterisk indicates differences (two-way ANOVA with Tukey’s post hoc test, p>0.05) between groups throughout the LD cycle.
Table 1
Statistical Analysis of chronobiological experiments in 3xTg-AD mice under jet lag protocol.
On top, the average (± SE) on Total, Day and Night locomotor activity (movements/bin cell) at 3, 8 and 13 Mo, between no transgenic (NoTg, n = sample size) and triple transgenic mice for Alzheimer disease (3xTg-AD). Below are shown the average (± SE) acrophases in Zeitgeber Time (ZT). Statistical differences inside each group (One way ANOVA) are indicated between data with same symbols. Differences between NoTg and 3xTgAD mice (between groups; Two-way ANOVA) are indicated with same letter.
| AVERAGE ACTIVITY (MOVEMENTS/10 MIN) | ||||
|---|---|---|---|---|
| INITIAL | TOTAL | NoTg(n = 7–10) | 3xTg-AD(n = 7–13) | |
| 3 Mo | 65.40 ± 14.20c | 37.94 ± 6.10c | ||
| 8 Mo | 37.90 ± 6.22 | 25.70 ± 5.16# | ||
| 13 Mo | 39.90 ± 8.50 | 57.25 ± 13.60# | ||
| DAY | ||||
| 3 Mo | 28.61 ± 8.84 | 17.8 ± 3.40 | ||
| 8 Mo | 19.20 ± 3.42 | 14.40 ± 2.23 | ||
| 13 Mo | 20.90 ± 4.64 | 20.90 ± 8.30 | ||
| NIGHT | ||||
| 3 Mo | 102.20 ± 26.20 | 59.43 ± 13.61 | ||
| 8 Mo | 56.60 ± 10.20 | 36.95 ± 8.24& | ||
| 13 Mo | 58.91 ± 15.14 | 93.62 ± 22.46& | ||
| ADVANCE | TOTAL | NoTg(n = 7–10) | 3xTg-AD(n = 7–13) | |
| 3 Mo | 52.20 ± 10.00 | 52.73 ± 5.16 | ||
| 8 Mo | 29.13 ± 5.70 e | 30.48 ± 9.40* | ||
| 13 Mo | 43.05 ± 10.60a,e | 82.70 ± 19.74a,* | ||
| DAY | ||||
| 3 Mo | 26.80 ± 9.64 | 21.33 ± 2.14† | ||
| 8 Mo | 17.75 ± 4.17 | 19.00 ± 5.45‡ | ||
| 13 Mo | 21.61 ± 9.40b | 51.30 ± 14.54b,†,‡ | ||
| NIGHT | ||||
| 3 Mo | 77.61 ± 13.50 | 84.12 + 9.80 | ||
| 8 Mo | 40.51 ± 7.82f | 42.00 ± 14.50@ | ||
| 13 Mo | 64.50 + 13.43f | 114.12 ± 28.32@ | ||
| DELAY | TOTAL | NoTg(n = 8–11) | 3xTg-AD(n = 7–13) | |
| 3 Mo | 58.22 ± 10.54d | 37.7 ± 6.65d | ||
| 8 Mo | 47.07 ± 6.00 | 33.56 ± 8.94 | ||
| 13 Mo | 43.55 ± 9.90 | 62.99 ±18.10 | ||
| DAY | ||||
| 3 Mo | 49.65 ± 19.34 | 21.10 ± 3.73 | ||
| 8 Mo | 37.66 ± 6.21 | 21.10 ± 7.13 | ||
| 13 Mo | 26.25 ± 8.20 | 33.10 ± 13.43 | ||
| NIGHT | ||||
| 3 Mo | 66.80 ± 12.10 | 54.33 ± 12.10 | ||
| 8 Mo | 56.50 ± 9.80 | 46.10 ± 11.80 | ||
| 13 Mo | 60.90 ± 14.40 | 92.90 ± 30.43 | ||
| ACROPHASES (ZT) | ||||
| INITIAL | NoTg(n = 8–11) | 3xTg-AD(n = 7–13) | ||
| 3 Mo | 17.61 ± 0.23 | 16.24 ± 0.26 | ||
| 8 Mo | 17.19 ± 0.49 | 16.12 ± 0.62 | ||
| 13 Mo | 16.53 ± 0.53 | 16.70 ± 0.43 | ||
| ADVANCE | ||||
| 3 Mo | 17.80 ± 0.49g | 15.40 ± 0.20g | ||
| 8 Mo | 17.30 ± 0.46h | 15.38 ± 0.36h | ||
| 13 Mo | 17.02 ± 0.37i | 15.22 ± 0.64i | ||
| DELAY | ||||
| 3 Mo | 16.60 ± 0.63 | 15.86 ± 0.32 | ||
| 8 Mo | 16.25 ± 0.53 | 15.67 ± 0.35 | ||
| 13 Mo | 14.40 ± 0.73 | 15.64 ± 0.82 | ||

Supplementary Figure 1
Average (±SE) of the onset (upper panels) and offset of locomotor activity (lower panels). The Onset is shown just for advances in LD schedules, while the offset is shown just for delays, to exclude the masking effect of light. Three ages are compared: 3, 8 and 13 Mo, respectively. Grey circles correspond to data from 3xTgAD mice, and black circles to its control group. Significant differences between groups are noted with a star (2way ANOVA, P0.05).

Figure 3
Average (±SE) of the phase angle (Y, min) between the onset of activity and lights-off. NoTg (black, n = 26) and 3xTg-AD (gray, n = 28) mice at initial (Ini), Advance (Adv) and Delay (Del) in LD conditions. The differences are indicated with brackets (two-way ANOVA per age, Tukey’s post hoc test, p < 0.05).

Figure 4
Average (±SE) analysis of the masking effect of light (% reduction). NoTg mice are represented in black and 3xTg-AD mice in gray bars. Significant differences among groups are indicated with brackets (two-way ANOVA per age, Tukey’s post hoc test, p < 0.05 test, n = 6–10 per group). Below, fragments of representative actograms.

Figure 5
Latency and amplitude analysis under mesopic conditions. In the upper panel, the latency of waves A and B. In the lower panel, the amplitude of waves A and B. Representative traces of ERG at 3 Mo, 8 Mo and 13 Mo. NoTg animals are depicted in black and 3xTg-AD animals in gray. Two-way ANOVA per age, Tukey’s post hoc test, p < 0.05 test, n = ±8. Calibration bar: 100 μV/100 msec.

Figure 6
Latency and amplitude analysis under mesopic conditions. In the upper panel, the latency of waves A and B. In the lower panel, the amplitude of waves A and B. Representative traces of ERG at 3 Mo, 8 Mo and 13 Mo. NoTg animals are depicted in black and 3xTg-AD animals in gray. Two-way ANOVA per age, Tukey’s post hoc test, p < 0.05 test, n = ±8. Calibration bar: 100 μV/100 msec.
