Sleep and Circadian Rhythm Dysfunction in Animal Models of Huntington's Disease

Abstract

Sleep and circadian disruption affects most individuals with Huntington's disease (HD) at some stage in their lives. Sleep and circadian dysregulation are also present in many mouse and the sheep models of HD. Here I review evidence for sleep and/or circadian dysfunction in HD transgenic animal models and discuss two key questions: 1) How relevant are such findings to people with HD, and 2) Whether or not therapeutic interventions that ameliorate deficits in animal models of HD might translate to meaningful therapies for people with HD.

Keywords: Cognitive function; neurodegeneration; thalamus.

Fig. 1

Disruption of circadian activity patterns in R6/2 mice with age. Typical double-plotted actograms show continuous recordings of a WT (left) and R6/2 (right) mice monitored for 1 week under LD light conditions (12 h light and 12 h dark) from 6-7 weeks (top panels) or 14-15 weeks (lower panels) of age. Mice were transferred into DD at 7 or 15 weeks of age, and their activity was recorded for an additional 7 d. This figure is an adapted version of Fig. 2 in Morton et al. [19].

Fig. 2

EEG powers during non-rapid eye movement sleep are different in transgenic and normal sheep under baseline conditions and after sleep deprivation. Heatmaps show the relative distribution of EEG powers in different frequency ranges denoted by Greek letters (δ, delta [0.5–4 Hz]; θ, theta [4–9 Hz]; α, alpha [9–14 Hz]; β, beta [14–35 Hz]; γ1, low-gamma [35–55 Hz]; γ2, high-gamma [55–120 Hz]) during an undisturbed light-off (Baseline Night 0; A) and on the day following a night of sleep deprivation (B) in transgenic and normal sheep. The arrows on A point to the period when the distribution of EEG powers show striking difference between normal and transgenic sheep at night. Color scales in each frequency range show the mean normalized EEG power values (per channel, per hour). For full results and experimental details see [63]. L and R = left or right hemisphere respectively. This figure is an adapted version of Figs. 5 and 7 in Vas et al. [63].