Sleep alterations in a mouse model of Spinocerebellar ataxia type 3

BackgroundSpinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder showing progressive neuronal loss in several brain areas and a broad spectrum of motor and non-motor symptoms, including ataxia and altered sleep. While sleep disturbances are known to play pathophysiologic roles in other neurodegenerative disorders, their impact on SCA3 is unknown. ObjectivesUsing state-of-the art spectrographic measurements, we sought to quantitatively characterize sleep electroencephalography (EEG) in a SCA3 transgenic mouse model with confirmed disease phenotype. MethodsWe first measured motor phenotypes in 18-31-week-old homozygous and hemizygous SCA3 YACMJD84.2 mice and non-transgenic wild-type littermate mice during lights-on and lights-off periods. We next implanted electrodes to obtain 12-hour (zeitgeber time 0-12) EEG recordings for three consecutive days when the mice were 26-36 weeks old. We then analyzed EEG-based sleep structure data to quantify differences between homozygous, hemizygous, and wild-type mice. ResultsCompared to wild-type littermates, SCA3 homozygous mice display: i) increased duration of rapid-eye movement sleep (REM) and fragmentation in all sleep and wake states; ii) higher beta power oscillations during REM and non-REM (NREM); and iii) additional spectral power band alterations during REM and wake. ConclusionsOur data show that sleep architecture and EEG spectral power are dysregulated in homozygous SCA3 mice, indicating that common sleep-related etiologic factors may underlie mouse and human SCA3 phenotypes.