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.
Barraud
Quentin
Q
Université Victor Segalen Bordeaux 2, Centre National de la Recherche Scientifique, Bordeaux Institute of Neuroscience, UMR 5227 and Centre Hospitalier et Universitaire de Bordeaux, 146 rue Léo Saignat, 33076 Bordeaux cedex, France.
Lambrecq
Virginie
V
Forni
Claude
C
McGuire
Steve
S
Hill
Michael
M
Bioulac
Bernard
B
Balzamo
Emmanuel
E
Bezard
Erwan
E
Tison
François
F
Ghorayeb
Imad
I
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D005260:Female; D020267:MPTP Poisoning / Q000139:chemically induced / Q000150:complications*; D008253:Macaca mulatta; D017286:Polysomnography / Q000379:methods; D012893:Sleep Wake Disorders / Q000209:etiology* / Q000473:pathology; D012895:Sleep, REM / Q000502:physiology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014851:Wakefulness
D015306:Biogenic Monoamines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase