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Amelioration of non-motor dysfunctions after transplantation of human dopamine neurons in a model of Parkinson's disease

Lelos, Mariah, Morgan, R. J., Kelly, Claire, Torres, Eduardo Miguel, Rosser, Anne Elizabeth and Dunnett, Stephen Bruce 2016. Amelioration of non-motor dysfunctions after transplantation of human dopamine neurons in a model of Parkinson's disease. Experimental Neurology 278 , pp. 54-61. 10.1016/j.expneurol.2016.02.003

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Abstract

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 ~ 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Medicine
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: Parkinson's disease; Non-motor symptoms; Visuo–spatial tasks; Cell transplantation; Ventral mesencephalon; Dopamine
Publisher: Elsevier
ISSN: 0014-4886
Funders: Medical Research Council
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 2 February 2016
Last Modified: 22 Jun 2019 22:21
URI: http://orca.cf.ac.uk/id/eprint/88139

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