Sleep dysfunction and EEG alterations in mice overexpressing alpha-synuclein

J Parkinsons Dis. 2014;4(3):531-539. doi: 10.3233/JPD-140374.

Abstract

Background: Sleep disruptions occur early and frequently in Parkinson's disease (PD). PD patients also show a slowing of resting state activity. Alpha-synuclein is causally linked to PD and accumulates in sleep-related brain regions. While sleep problems occur in over 75% of PD patients and severely impact the quality of life of patients and caregivers, their study is limited by a paucity of adequate animal models.

Objective: The objective of this study was to determine whether overexpression of wildtype alpha-synuclein could lead to alterations in sleep patterns reminiscent of those observed in PD by measuring sleep/wake activity with rigorous quantitative methods in a well-characterized genetic mouse model.

Methods: At 10 months of age, mice expressing human wildtype alpha-synuclein under the Thy-1 promoter (Thy1-aSyn) and wildtype littermates underwent the subcutaneous implantation of a telemetry device (Data Sciences International) for the recording of electromyograms (EMG) and electroencephalograms (EEG) in freely moving animals. Surgeries and data collection were performed without knowledge of mouse genotype.

Results: Thy1-aSyn mice showed increased non-rapid eye movement sleep during their quiescent phase, increased active wake during their active phase, and decreased rapid eye movement sleep over a 24-h period, as well as a shift in the density of their EEG power spectra toward lower frequencies with a significant decrease in gamma power during wakefulness.

Conclusions: Alpha-synuclein overexpression in mice produces sleep disruptions and altered oscillatory EEG activity reminiscent of PD, and this model provides a novel platform to assess mechanisms and therapeutic strategies for sleep dysfunction in PD.

Keywords: EEG; Parkinson disease; Thy1-aSyn mice; gamma oscillations; implantable telemetry; power spectra; rapid eye movement sleep.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / physiopathology*
  • Disease Models, Animal*
  • Electroencephalography
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Parkinson Disease / complications*
  • Sleep Wake Disorders / etiology*
  • Sleep Wake Disorders / physiopathology*
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism*

Substances

  • SNCA protein, human
  • alpha-Synuclein