Sleep and EEG features in genetic models of Down syndrome

Abstract

Down syndrome is characterized by a host of behavioral abnormalities including sleep disturbances. Sleep and EEG was studied at the age of 3 months in two mouse models of the condition, Ts65Dn and Ts1Cje, carrying one extra copy of partially overlapping segments of the mmu chromosome 16 (equivalent to the human chromosome 21). We found that the Ts65Dn mice showed increased waking amounts at the expense of non-REM sleep, increased theta power during sleep and a delayed sleep rebound after sleep deprivation. In contrast, Ts1Cje had limited sleep and EEG abnormalities, showing only a delayed sleep rebound after sleep deprivation and no difference in theta power. We previously found that mice over-expressing the human APPwt transgene, a gene triplicated in Ts65Dn but not Ts1Cje, also show increased wake and theta power during sleep. These results demonstrate abnormalities in sleep and EEG in Ts65Dn mice and underscore a possible correlation between App overexpression and hippocampal theta oscillations.

Fig. 1

Nychthemeral distribution of wake and sleep amounts in baseline. (A) Wake, (B) NREM and (C) REM sleep amounts per 3 h bouts in Ts mice versus 2N mice. Left panel Ts65Dn (bold line) versus 2N and right panel Ts1Cje (bold line) versus 2N. Ordinates: amounts in minutes; abscises: clock time in 3 h bouts. Values are expressed as mean ± SEM (n=7 per genotype). ^*p<0.05 and ^**p<0.01 (ANOVA).

Fig. 2

Behavioral states spectral profiles in baseline. Left panel: Ts65Dn (marked line) versus 2N mice (plain line); right panel: Ts1Cje (marked line) versus 2N (plain line). (A) Wake, (B) NREM and (C) REM sleep. In ordinates, EEG power density are the mean % of total EEG power ± SEM (n = 7 per genotype) for 0.25 Hz frequency bins between 0.25 and 25 Hz (in abscises). The delta and theta ranges used for power band calculations are shown above the corresponding abscise. ^**p<0.01 (ANOVA).

Fig. 3

Effects of SD over the 4-h subsequent rebound period versus baseline. Left: Ts65Dn (black bar) versus 2N mice (white bar); right: Ts1Cje (black bar) versus 2N (white bar). (A) Sleep latency after SD in mean min ± SEM (n=6 per genotype). (B) Sleep amounts variations after SD in mean % of variation versus individual base line values ± SEM (n=6 per genotypes). (C) NREM sleep delta power % of variation versus baseline values ± SEM (n=6 per genotypes). ^*p<0.05 and ^**p<0.01 (ANOVA).