Sleep disorders in Parkinson's disease: the contribution of the MPTP non-human primate model

To replicate the sleep-wake disorders of Parkinson's disease (PD) and to understand the temporal relationship between these sleep disturbances and the occurrence of parkinsonism, we performed long-term continuous electroencephalographic monitoring of vigilance states in unrestrained rhesus monkeys using an implanted miniaturized telemetry device and tested the effect of MPTP intoxication on their sleep-wake organization. MPTP injection yielded a dramatic disruption of sleep-wake architecture with reduced sleep efficacy that persisted years after MPTP administration. Primary deregulation of REM sleep and increased daytime sleepiness occurring before the emergence of motor symptoms were a striking feature of the MPTP effect. This was concomitant with a breakdown of dopaminergic homeostasis, as evidenced by decreased dopamine turnover measured after a single MPTP injection. In the long term, partial re-emergence of REM sleep paralleled the partial adaptation to parkinsonism, the latter being known to result from compensatory mechanisms within the dopaminergic system. Altogether, these findings highlight the suitability of the MPTP model of PD as a tool to model the sleep/wake disturbances of the human disease. Ultimately, this may help in deciphering the specific role of dopamine depletion in the occurrence of these disorders.