Transgenic Fatal Familial Insomnia Mice Indicate Prion Infectivity-Independent Mechanisms of Pathogenesis and Phenotypic Expression of Disease
Fig 5
Tg(FFI) mice show an altered response to sleep deprivation.
Time course of the loss and recovery of time spent in rapid eye movement (REM) (A) and non-rapid eye movement (NREM) (B) sleep, during and after sleep deprivation. Values were from 8 non-Tg/Prnp+/+, 10 non-Tg/Prnp0/0, 9 Tg(FFI-26)/Prnp0/0 and 8 Tg(FFI-26)/Prnp+/0. Mice were kept awake during the first 6 h of the light phase (crosshatched bar) by gentle handling, and allowed to sleep freely in the next 18 h. The black bar indicates the dark portion of the light-dark cycle. REM and NREM sleep were calculated hourly for each animal as the difference between the amount of time spent in a given state (REM or NREM sleep) during and after sleep deprivation, and the amount spent in the corresponding hour during baseline conditions (undisturbed). The hour-by-hour differences were then summed to obtain a cumulative curve. Data (means ± SEM) are presented in 2-h intervals. Single symbols: p < 0.05; double symbols: p < 0.01. *, Tg(FFI-26)/Prnp0/0 vs non-Tg/Prnp0/0; °, Tg(FFI-26)/Prnp0/0 vs. non-Tg/Prnp+/+; §, Tg(FFI-26)/Prnp0/0 vs. Tg(FFI-26)/Prnp+/0; #, Tg(FFI-26)/Prnp+/0 vs. non-Tg/Prnp+/+. A mixed model analysis of variance for repeated measures was done on 6 h blocks. Between-strains post-hoc comparisons by one-way ANOVA with Bonferroni correction: (panel A) 0–6 h: F3,101 = 4.98, p = 0.003; 7–12 h: F3,101 = 5.25, p = 0.002; 13–18 h: F3,101 = 2.88, p = 0.05; 19–24 h: F3,101 = 3.30, p = 0.023. (panel B) 0–6 h: F3,101 = 1.01, p = 0.391; 7–12 h: F3,101 = 1.78, p = 0.156; 13–18 h: F3,101 = 3.76, p = 0.013; 19–24 h: F3,101 = 3.97, p = 0.010.