期刊
EXPERIMENTAL NEUROLOGY
卷 278, 期 -, 页码 54-61出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2016.02.003
关键词
Parkinson's disease; Non-motor symptoms; Visuo-spatial tasks; Cell transplantation; Ventral mesencephalon; Dopamine
资金
- Medical Research Council [G1001257]
- European Community's Seventh Framework Programme, NeuroStemCell [222943]
- European Community's Seventh Framework Programme, NeuroStemCellRepair [602278]
- MRC [G1001257, MR/M02475X/1] Funding Source: UKRI
- Medical Research Council [MR/L010305/1, MR/M02475X/1, G1001257] Funding Source: researchfish
Background: Patients suffering from Parkinson's disease (PD) display cognitive and neuropsychiatric dysfunctions, especially with disease progression. Although these impairments have been reported to impact more heavily upon a patient's quality of life than any motor dysfunctions, there are currently no interventions capable of adequately targeting these non-motor deficits. Objectives: Utilizing a rodent model of PD, we investigated whether cell replacement therapy, using intrastriatal transplants of human-derived ventral mesencephalic (hVM) grafts, could alleviate cognitive and neuropsychiatric, as well as motor, dysfunctions. Methods: Rats with unilateral 6-hydroxydopamine lesions to the medial forebrain bundle were tested on a complex operant task that dissociates motivational, visuospatial and motor impairments sensitive to the loss of dopamine. A subset of lesioned rats received intrastriatal hVM grafts of similar to 9 weeks gestation. Post-graft, rats underwent repeated drug-induced rotation tests and were tested on two versions of the complex operant task, before post-mortem analysis of the hVM tissue grafts. Results: Post-graft behavioural testing revealed that hVM grafts improved non-motor aspects of task performance, specifically visuospatial function and motivational processing, as well as alleviating motor dysfunctions. Conclusions: We report the first evidence of human VM cell grafts alleviating both non-motor and motor dysfunctions in an animal model of PD. This intervention, therefore, is the first to improve cognitive and neuropsychiatric symptoms long-term in a model of PD. (C) 2016 The Authors. Published by Elsevier Inc.
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