TY - JOUR
T1 - Amelioration of non-motor dysfunctions after transplantation of human dopamine neurons in a model of Parkinson's disease
AU - Lelos, M. J.
AU - Morgan, R. J.
AU - Kelly, C. M.
AU - Torres, E. M.
AU - Rosser, A. E.
AU - Dunnett, S. B.
N1 - Publisher Copyright:
© 2016 Published by Elsevier Inc.
PY - 2016/2/10
Y1 - 2016/2/10
N2 - 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.
AB - 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.
KW - Cell transplantation
KW - Dopamine
KW - Non-motor symptoms
KW - Parkinson's disease
KW - Ventral mesencephalon
KW - Visuo-spatial tasks
UR - http://www.scopus.com/inward/record.url?scp=84957548768&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2016.02.003
DO - 10.1016/j.expneurol.2016.02.003
M3 - Article
C2 - 26851542
AN - SCOPUS:84957548768
SN - 0014-4886
VL - 278
SP - 54
EP - 61
JO - Experimental Neurology
JF - Experimental Neurology
ER -
