Abstract
Down syndrome is a common disorder associated with intellectual disability in humans. Among a variety of severe health problems, patients with Down syndrome exhibit disrupted sleep and abnormal 24-h rest/activity patterns. The transchromosomic mouse model of Down syndrome, Tc1, is a trans-species mouse model for Down syndrome, carrying most of human chromosome 21 in addition to the normal complement of mouse chromosomes and expresses many of the phenotypes characteristic of Down syndrome. To date, however, sleep and circadian rhythms have not been characterized in Tc1 mice. Using both circadian wheel-running analysis and video-based sleep scoring, we showed that these mice exhibited fragmented patterns of sleep-like behaviour during the light phase of a 12:12-h light/dark (LD) cycle with an extended period of continuous wakefulness at the beginning of the dark phase. Moreover, an acute light pulse during night-time was less effective in inducing sleep-like behaviour in Tc1 animals than in wild-type controls. In wheel-running analysis, free running in constant light (LL) or constant darkness (DD) showed no changes in the circadian period of Tc1 animals although they did express subtle behavioural differences including a reduction in total distance travelled on the wheel and differences in the acrophase of activity in LD and in DD. Our data confirm that Tc1 mice express sleep-related phenotypes that are comparable with those seen in Down syndrome patients with moderate disruptions in rest/activity patterns and hyperactive episodes, while circadian period under constant lighting conditions is essentially unaffected.
Highlights
Introduction of an acutelight pulse (LP) in the dark phase of the LD cycle should rapidly induce sleep in mice (Lupi et al 2008; Muindi et al 2013)
Using a conventional circadian wheel-running recording system, mice of both genotypes, Tc1 carrier mice and wild-type littermate controls, showed normal photoentrainment under a 12:12 LD cycle, with 90% of wheel-running activity occurring in the nocturnal phase and similar alpha (Table 1, Figs. 1 and 2a)
Comparison of wheel-running activity showed a trend towards a delay in the acrophase of wheel-running activity at the beginning of the dark phase for Tc1 animals, this was not significant (Fig. 2a, wild-type acrophase at 22.00 ± 0.41 h and Tc1 at 20.96 ± 0.25 h, F 1,17 = 1.553, P = 0.230)
Summary
Introduction of an acuteLP in the dark phase of the LD cycle should rapidly induce sleep in mice (Lupi et al 2008; Muindi et al 2013). Using a conventional circadian wheel-running recording system, mice of both genotypes, Tc1 carrier mice and wild-type littermate controls, showed normal photoentrainment under a 12:12 LD cycle, with 90% of wheel-running activity occurring in the nocturnal phase and similar alpha
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