early presymptomatic and long-term changes of rest activity cycles and cognitive behavior in a mptp-monkey model of parkinsons disease早期和其他活动的长期变化周期发生前症状和认知行为mptp-monkey帕金森病模型.pdfVIP

Early Presymptomatic and Long-Term Changes of Rest Activity Cycles and Cognitive Behavior in a MPTP-Monkey Model of Parkinson’s Disease Julien Vezoli1,2,3*, Karim Fifel1,2, Vincent Leviel1,2, Colette Dehay1,2, Henry Kennedy1,2, Howard M. Cooper1,2*, Claude Gronfier1,2, Emmanuel Procyk1,2 ´ ¨ 1 Inserm, U846, Stem Cell and Brain Research Institute, Bron, France, 2 Universite de Lyon, Lyon 1, UMR-S 846, Lyon, France, 3 Ernst Strungmann Institute (ESI) in Cooperation with Max Planck Society, Frankfurt, Germany Abstract Background: It is increasingly recognized that non-motor symptoms are a prominent feature of Parkinson’s disease and in the case of cognitive deficits can precede onset of the characteristic motor symptoms. Here, we examine in 4 monkeys chronically treated with low doses of the neurotoxin MPTP the early and long-term alterations of rest-activity rhythms in relationship to the appearance of motor and cognitive symptoms. Methodology/Principal Findings: Behavioral activity recordings as well as motor and cognitive assessments were carried out continuously and in parallel before, during and for several months following MPTP-treatment (12–56 weeks). Cognitive abilities were assessed using a task that is dependent on the functional integrity of the fronto-striatal axis. Rest-activity cycles were monitored continuously using infrared movement detectors of locomotor activity. Motor impairment was evaluated using standardized scales for primates. Results show that MPTP treatment led to an immediate alteration (within one week) of rest-activity cycles and cognitive deficits. Parkinsonian motor deficits only became apparent 3 to 5 weeks after initiating chronic MPTP administration. In three of t