期刊
ADVANCED SCIENCE
卷 9, 期 10, 页码 -出版社
WILEY
DOI: 10.1002/advs.202103827
关键词
circadian rhythms; cognition and motor control; embryonic stem cells; neural precursors; nonhuman primate low-dose MPTP
资金
- Region Rhone-Alpes
- Fondation de France
- Fondation Caisse d'Epargne Rhone-Alpes Lyon
- Rhone-Alpes cible [11-010869]
- Fondation Neurodis
- Fondation pour la Recherche Medicale [DEQ20160334943, DEQ20170336757]
- Cluster Handicap Vieillissement Neurosciences Rhone-Alpes [P6-2005 IST-1583, FP7-2007 ICT-216593]
- Infrastructure Nationale en Biologie et Sante INGESTEM [ANR-11-INBS-0009]
- IHU-B CESAME [ANR-10-IBHU-003]
- LabEX CORTEX [ANR-11 LABX-0042]
- LabEX DEVweCAN of the Universite de Lyon [ANR-10-LABX-0061, ANR-11-IDEX-0007, 2019-ANR-LABX-02]
- Agence Nationale de la Recherche [ANR-11-BSV4-501]
- FRC APE13 Rotary - Espoir en Tete
Parkinson's disease (PD) has a long and variable development process, and can cause various symptoms such as sleep and biological rhythm disorders. In a study using a monkey model of PD, neural precursor grafts were able to restore both motor and cognitive functions, and the degree of graft integration and striatal dopaminergic innervation correlated with the recovery.
Parkinson's disease (PD) evolves over an extended and variable period in humans; years prior to the onset of classical motor symptoms, sleep and biological rhythm disorders develop, significantly impacting the quality-of-life of patients. Circadian-rhythm disorders are accompanied by mild cognitive deficits that progressively worsen with disease progression and can constitute a severe burden for patients at later stages. The gold-standard 6-methyl-1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) macaque model of PD recapitulates the progression of motor and nonmotor symptoms over contracted periods of time. Here, this multidisciplinary/multiparametric study follows, in five animals, the steady progression of motor and nonmotor symptoms and describes their reversal following grafts of neural precursors in diverse functional domains of the basal ganglia. Results show unprecedented recovery from cognitive symptoms in addition to a strong clinical motor recuperation. Both motor and cognitive recovery and partial circadian rhythm recovery correlate with the degree of graft integration, and in a subset of animals, with in vivo levels of striatal dopaminergic innervation and function. The present study provides empirical evidence that integration of neural precursors following transplantation efficiently restores function at multiple levels in parkinsonian nonhuman primates and, given interindividuality of disease progression and recovery, underlines the importance of longitudinal multidisciplinary assessments in view of clinical translation.
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