title: Sleep dysfunction and EEG alterations in mice overexpressing alpha-synuclein.
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.
authors.affiliation: Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: McDowell
authors.affiliation: Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Shin
authors.affiliation: Department of Physiology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Roos
authors.affiliation: Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Chesselet
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004569:Electroencephalography; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010300:Parkinson Disease / Q000150:complications*; D012893:Sleep Wake Disorders / Q000209:etiology* / Q000503:physiopathology*; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: C497604:SNCA protein, human; D051844:alpha-Synuclein
keywords: EEG; Parkinson disease; Thy1-aSyn mice; gamma oscillations; implantable telemetry; power spectra; rapid eye movement sleep