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Induced Cognitive Impairments Reversed by Grafts of Neural Precursors: A Longitudinal Study in a Macaque Model of Parkinson's Disease

Authors :
Florence Wianny
Kwamivi Dzahini
Karim Fifel
Charles Robert Eden Wilson
Agnieszka Bernat
Virginie Dolmazon
Pierre Misery
Camille Lamy
Pascale Giroud
Howard Michael Cooper
Kenneth Knoblauch
Emmanuel Procyk
Henry Kennedy
Pierre Savatier
Colette Dehay
Julien Vezoli
Source :
Advanced Science, Vol 9, Iss 10, Pp n/a-n/a (2022)
Publication Year :
2022
Publisher :
Wiley, 2022.

Abstract

Abstract 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.

Details

Language :
English
ISSN :
21983844 and 46149414
Volume :
9
Issue :
10
Database :
Directory of Open Access Journals
Journal :
Advanced Science
Publication Type :
Academic Journal
Accession number :
edsdoj.6c2033c46149414da9b32938aff53854
Document Type :
article
Full Text :
https://doi.org/10.1002/advs.202103827