Abnormally abrupt transitions from sleep-to-wake in Huntington's disease sheep (Ovis aries) are revealed by automated analysis of sleep/wake transition dynamics

PLoS One. 2021 May 13;16(5):e0251767. doi: 10.1371/journal.pone.0251767. eCollection 2021.

Abstract

Sleep disturbance is a common and disruptive symptom of neurodegenerative diseases such as Alzheimer's and Huntington's disease (HD). In HD patients, sleep fragmentation appears at an early stage of disease, although features of the earliest sleep abnormalities in presymptomatic HD are not fully established. Here we used novel automated analysis of quantitative electroencephalography to study transitions between wake and non-rapid eye movement sleep in a sheep model of presymptomatic HD. We found that while the number of transitions between sleep and wake were similar in normal and HD sheep, the dynamics of transitions from sleep-to-wake differed markedly between genotypes. Rather than the gradual changes in EEG power that occurs during transitioning from sleep-to-wake in normal sheep, transition into wake was abrupt in HD sheep. Furthermore, transitions to wake in normal sheep were preceded by a significant reduction in slow wave power, whereas in HD sheep this prior reduction in slow wave power was far less pronounced. This suggests an impaired ability to prepare for waking in HD sheep. The abruptness of awakenings may also have potential to disrupt sleep-dependent processes if they are interrupted in an untimely and disjointed manner. We propose that not only could these abnormal dynamics of sleep transitions be useful as an early biomarker of HD, but also that our novel methodology would be useful for studying transition dynamics in other sleep disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Electroencephalography
  • Female
  • Humans
  • Huntington Disease / complications*
  • Huntington Disease / physiopathology
  • Polysomnography / methods
  • Sheep, Domestic
  • Sleep / physiology
  • Sleep Deprivation / diagnosis
  • Sleep Deprivation / etiology
  • Sleep Deprivation / physiopathology*
  • Wakefulness / physiology

Associated data

  • Dryad/10.5061/dryad.q2bvq83jh

Grants and funding

This work was funded by a grant to AJM from the CHDI Foundation (chdifoundation.org). There is no grant number associated with the received grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.