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

Sleep dysfunction and EEG alterations in mice overexpressing alpha-synuclein.

Author information

1
Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
2
Department of Physiology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

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

PMID:
24867919
DOI:
10.3233/JPD-140374
[Indexed for MEDLINE]
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