Amelioration of non-motor dysfunctions after transplantation of human dopamine neurons in a model of Parkinson's disease.
Exp Neurol
; 278: 54-61, 2016 Apr.
Article
em En
| MEDLINE
| ID: mdl-26851542
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Transtornos da Percepção
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Transtornos Cognitivos
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Modelos Animais de Doenças
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Neurônios Dopaminérgicos
Tipo de estudo:
Etiology_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Exp Neurol
Ano de publicação:
2016
Tipo de documento:
Article