Age-related differences in sleep disturbances in rat models of preclinical Parkinson's disease

Abstract

To describe the changes in temporal characteristics of sleep-wake cycle, which can serve as non-motor manifestations of an early stage of Parkinson's disease (PD), using the model of preclinical PD in rats of two age groups. A prolonged (up to 21 days) model of preclinical PD in middle-aged (7-8 month) and aged (19-20 month) rats was created. The model was based on cumulative inhibition of proteasomal system of the brain caused by intranasal administration of lactacystin, a specific proteasome inhibitor. Polysomnographic data were recorded daily using telemetric Dataquest A.R.T. System (DSI, USA) in unrestrained animals. Aging was accompanied with increased sleepiness during the active (dark) phase of the day (as was implied by a two-fold increase in the total time of drowsiness) and with 1.5-fold growth of light sleep during the inactive phase of the day. A common feature of sleep disturbances in the model of preclinical PD in both middle-aged and aged rats was hypersomnia during the active phase of the day. It was suggested to be similar to the excessive daytime sleepiness in humans. Hypersomnolence was more pronounced in aged rats because it added to sleepiness developing with aging. In both age groups, the model of preclinical PD was also associated with a decrease in EEG delta power during slow-wave sleep. It is considered dangerous because it might represent the decrease in protein synthesis rate and the weakening of restorative processes in neurons, occurring with the prolonged inhibition of proteasomal system of the brain. Sleep disturbances, identified the model of preclinical PD in rats of different age, may be recommended for clinical validation as low-cost early signs indicating the initial stage of PD.