Category: Parkinson's Disease: Non-Motor Symptoms
Objective: To examine sleep architecture in a commonly studied mouse model of Parkinson’s disease (PD) to better understand underlying circuit mechanisms of sleep disturbances in PD.
Background: While classically defined by its motor features, PD has numerous and often disabling non-motor manifestations, which profoundly impact quality of life. Sleep disturbances are some of the most commonly reported non-motor symptoms of PD, and can include insomnia, hypersomnia, REM sleep behavior disorder and daytime sleepiness. There is no clear consensus on how proportions of wakefulness, non-REM (NREM), and REM sleep are altered in PD, but sleep fragmentation is proposed as a core characteristic. The basal ganglia are an interconnected set of subcortical nuclei known to be central to the motor phenotype seen in Parkinson’s disease, but circuits underlying sleep disturbances in PD are less clear. It has therefore been challenging to target treatments for sleep symptoms in PD.
Method: Mice underwent unilateral stereotaxic injection of the neurotoxin 6-hydroxydopamine (6-OHDA) or saline in the medial forebrain bundle to generate parkinsonian mice and controls. Parkinsonian mice and controls were then implanted with EEG and EMG recording devices for continuous recording of sleep. Mouse sleep was recorded for a period of 6 hours during the light cycle. Sleep states were classified as either Wake, REM, or NREM based upon spectral analysis. The number of sleep state transitions per minute were calculated as a measure of sleep fragmentation.
Results: Mice injected with 6-OHDA show near complete loss of dopamine neurons measured by tyrosine hydroxylase expression compared to the uninjected side. Parkinsonian mice demonstrate decreased movement velocity and rotate ipsilateral to the injected side compared to saline treated controls. We hypothesize that extended sleep recording in Parkinsonian mice and controls will show differences in the number of sleep state transitions.
Conclusion: We are testing the hypothesis that Parkinsonian mice demonstrate differences in sleep state transitions compared to saline treated controls, which would suggest that loss of dopamine in this PD model leads to changes in sleep circuitry. Next steps include testing this hypothesis and examining the circuit mechanisms driving these changes using electrophysiological and optogenetic techniques.
To cite this abstract in AMA style:
P. Marcott, A. Nelson. Dissecting Neural Circuits Regulating Sleep State Transitions in a Mouse Model of Parkinson’s Disease [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/dissecting-neural-circuits-regulating-sleep-state-transitions-in-a-mouse-model-of-parkinsons-disease/. Accessed October 7, 2024.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/dissecting-neural-circuits-regulating-sleep-state-transitions-in-a-mouse-model-of-parkinsons-disease/