Abnormal patterns of sleep and EEG power distribution during non-rapid eye movement sleep in the sheep model of Huntington's disease

Sleep disruption is a common invisible symptom of neurological dysfunction in Huntington's disease (HD) that takes an insidious toll on well-being of patients. Here we used electroencephalography (EEG) to examine sleep in 6 year old OVT73 transgenic sheep (Ovis aries) that we used as a presymptomatic model of HD. We hypothesized that despite the lack of overt symptoms of HD at this age, early alterations of the sleep-wake pattern and EEG powers may already be present. We recorded EEG from female transgenic and normal sheep (5/group) during two undisturbed ‘baseline’ nights with different lighting conditions. We then recorded continuously through a night of sleep disruption and the following 24 h (recovery day and night). On baseline nights, regardless of whether the lights were on or off, transgenic sheep spent more time awake than normal sheep particularly at the beginning of the night. Furthermore, there were significant differences between transgenic and normal sheep in both EEG power and its pattern of distribution during non-rapid eye movement (NREM) sleep. In particular, there was a significant decrease in delta (0.5–4 Hz) power across the night in transgenic compared to normal sheep, and the distributions of delta, theta and alpha oscillations that typically dominate the EEG in the first half of the night of normal sheep were skewed so they were predominant in the second, rather than the first half of the night in transgenic sheep. Interestingly, the effect of sleep disruption on normal sheep was also to skew the pattern of distribution of EEG powers so they looked more like that of transgenic sheep under baseline conditions. Thus it is possible that transgenic sheep exist in a state that resemble a chronic state of physiological sleep deprivation. During the sleep recovery period, normal sheep showed a significant ‘rebound’ increase in delta power with frontal dominance. A similar rebound was not seen in transgenic sheep, suggesting that their homeostatic response to sleep deprivation is abnormal. Although sleep abnormalities in early stage HD patients are subtle, with patients often unaware of their existence, they may contribute to impairment of neurological function that herald the onset of disease. A better understanding of the mechanisms underlying EEG abnormalities in early stage HD would give insight into how, and when, they progress into the sleep disorder. The transgenic sheep model is ideally positioned for studies of the earliest phase of disease when sleep abnormalities first emerge