Abstract
BackgroundAs of late, dopaminergic neurotransmission has been recognized to be involved in the generation of sleep disturbances. Increasing evidence shows that sleep disturbances in Parkinson's disease (PD) patients are mostly related to the disease itself, rather than being a secondary phenomenon. Evidence contained in the literature lends support to the hypothesis that the dopaminergic nigrostriatal pathway is closely involved in the regulation of sleep patterns.Methodology/Principal FindingsTo test this hypothesis we examined the electrophysiological activity along the sleep-wake cycle of rats submitted to a surgically induced lesion of the SNpc by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We demonstrated that a 50% lesion of the substantia nigra pars compacta (SNpc) suffices to produce disruptions of several parameters in the sleep-wake pattern of rats. A robust and constant decrease in the latency to the onset of slow wave sleep (SWS) was detected throughout the five days of recording in both light [F(22.16) = 72.46, p<0.0001] and dark [F(22.16) = 75.0, p<0.0001] periods. Also found was a pronounced increase in the percentage of sleep efficiency during the first four days of recording [F(21.15) = 21.48, p<0.0001], in comparison to the sham group. Additionally, the reduction in the SNpc dopaminergic neurons provoked an ablation in the percentage of rapid eye movement sleep (REM) during three days of the sleep-wake recording period with a strong correlation (r = 0.91; p<0.0001) between the number of dopaminergic neurons lost and the percentage decrease of REM sleep on the first day of recording. On day 4, the percentage of REM sleep during the light and dark periods was increased, [F(22.16) = 2.46, p<0.0007], a phenomenon consistent with REM rebound.Conclusions/SignificanceWe propose that dopaminergic neurons present in the SNpc possess a fundamental function in the regulation of sleep processes, particularly in promoting REM sleep.
Highlights
Parkinson’s disease (PD) is a neurodegenerative disorder mainly characterized by motor deficits generated by the decrease of dopaminergic neurons within the substantia nigra pars compacta (SNpc)
To test this hypothesis we examined the electrophysiological activity along the sleep-wake cycle of rats submitted to a surgically induced lesion of the SNpc induced by 1methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
The main findings are that the dopaminergic neurons located within the SNpc played an important role in regulating sleep patterns in rats, and that disturbances in this particular neuronal population produced severe complications in all the sleep parameters examined, especially in rapid eye movement sleep (REM) sleep
Summary
Parkinson’s disease (PD) is a neurodegenerative disorder mainly characterized by motor deficits generated by the decrease of dopaminergic neurons within the substantia nigra pars compacta (SNpc). Along with the influence of dopaminergic neurotransmission on generating sleep disturbances, the evidence further supports the hypothesis that the dopaminergic nigrostriatal pathway, is fundamental in the regulation of sleep patterns. To test this hypothesis we examined the electrophysiological activity along the sleep-wake cycle of rats submitted to a surgically induced lesion of the SNpc induced by 1methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To test this hypothesis we examined the electrophysiological activity along the sleep-wake cycle of rats submitted to a surgically induced lesion of the SNpc by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We propose that dopaminergic neurons present in the SNpc possess a fundamental function in the regulation of sleep processes, in promoting REM sleep
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