Sleep alterations in a mouse model of Spinocerebellar ataxia type 3

Abstract

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.