B26 Sleep and EEG Abnormalities in Huntington's Disease Mice

There is good evidence to suggest that Huntington9s disease (HD) patients have sleep disturbances that may deleteriously affect their cognitive performance, affective behaviour, and general well-being. Although sleep studies in HD patents were originally carried out more than 20 years ago, a comprehensive description of the progression of sleep and EEG changes in HD has been never conducted. Here we analysed the sleep and EEG changes in a transgenic mouse model of HD. We used R6/2 mice that carry a fragment of the HTT gene including a moderately long (250) CAG repeat. These mice show a progressive neurological phenotype including cognitive abnormalities and circadian disruption. R6/2 mice and their wild-type littermates were instrumented with EEG/EMG electrodes, and 24 h recordings were made using Neurologgers at a late stage of the disease (17–18 weeks of age). The signals were digitally filtered and scored in 10-s epochs as Wake, non-REM sleep, or REM sleep using SleepSign (Kissei Comtec CO., LTD., Japan). We then visually inspected all scoring and made corrections when appropriate. In addition to the standard scoring, we performed a spectral analysis of the sleep EEG by means of fast Fourier transformation as this procedure allows a much more sensitive and detailed description of EEG changes than the conventional staging. Our preliminary data show that sleep and EEG are significantly disrupted in R6/2 mice by 18 weeks of age. We found that R6/2 mice have fragmented sleep during the lights-on period as well as severe REM sleep abnormalities. R6/2 mice showed twice as much REM sleep as WT mice and a slower but highly synchronised theta activity during REM sleep. Defining the abnormalities of sleep that exist in HD and understanding their influence on other disease-related features is important for enabling clinicians to initiate appropriate investigations and to instigate treatments that could dramatically improve quality of life in HD patients.