Progressive sleep and electroencephalogram changes in mice carrying the Huntington's disease mutation

Sleep disturbances in Huntington's disease may be deleterious to the cognitive performance, affective behaviour, and general well-being of patients, but a comprehensive description of the progression of changes in sleep and electroencephalogram in Huntington's disease has never been conducted. Here we studied sleep and electroencephalogram disturbances in a transgenic mouse model of Huntington's disease (R6/2 mice). We implanted 10 R6/2 mice and five wild-type littermates with electromyography electrodes, frontofrontal and frontoparietal electroencephalogram electrodes and then recorded sleep/wake behaviour at presymptomatic, symptomatic and late stages of the disease. In addition to sleep-wake scoring, we performed a spectral analysis of the sleep electroencephalogram. We found that sleep and electroencephalogram were already significantly disrupted in R6/2 mice at 9 weeks of age (presymptomatic stage). By the time they were symptomatic, R6/2 mice were unable to maintain long periods of wakefulness and had an increased propensity for rapid eye movement sleep. In addition, the peak frequency of theta rhythm was shifted progressively from 7 Hz to 6 Hz during rapid eye movement sleep, whereas slow wave activity decreased gradually during non-rapid eye movement sleep. Finally, as the disease progressed, an abnormal electroencephalogram gamma activity (30-40 Hz) emerged in R6/2 mice irrespective of sleep states. This is reminiscent of the increased gamma power described in schizophrenic patients during sleep and events of psychosis. Gaining a better understanding of sleep and electroencephalogram changes in patients with Huntington's disease should be a priority, since it will enable clinicians to initiate appropriate investigations and to instigate treatments that could dramatically improve patients' quality of life.