Amelioration of non-motor dysfunctions after transplantation of human dopamine neurons in a model of Parkinson's disease
MetadataShow full item record
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.
Lelos, M. J.,Morgan, R. J.,Kelly, C.M.,Torres, E. M.,Rosser, A. E., Dunnett, S. B. (2016) 'Amelioration of non-motor dysfunctions after transplantation of human dopamine neurons in a model of Parkinson's disease', Experimental Neurology, Volume 278, April 2016, Pages 54–61.
This article was published in Experimental Neurology on 4th February 2016 (online), available at http://dx.doi.org/10.1016/j.expneurol.2016.02.003
- Import 
Showing items related by title, author, subject and abstract.
Dopamine-rich grafts alleviate deficits in contralateral response space induced by extensive dopamine depletion in rats Heuer, Andreas; Lelos, Mariah; Kelly, Claire; Torres, Eduardo; Dunnett, Stephen (Elsevier, 2013)Unilateral infusion of 6-hydroxydopamine into the nigro-striatal pathway in the rat is the most common dopamine lesion model of Parkinson's disease. In the present study, we explore the impact of near complete unilateral ...
Dopaminergic Progenitors Derived From Epiblast Stem Cells Function Similarly to Primary VM-Derived Progenitors When Transplanted Into a Parkinson’s Disease Model Precious, Sophie; Smith, Gaynor; Heuer, Andreas; Jaeger, Ines; Lane, Emma; Dunnett, Stephen; Li, Meng; Kelly, Claire; Rosser, Anne (Frontiers Media, 2020-04-07)Neural transplantation in neurodegenerative diseases such as Parkinson’s disease (PD) offers to replace cells lost during the progression of the disease process. Primary fetal ventral mesencephalon (VM), the origin of bona ...
Rumpf, M.C.; Cronin, J.B.; Mohamad, I.N.; Oliver, Jon; Hughes, Michael G. (Elsevier, 2014)Objectives = A possible injury risk factor is limb asymmetry, which may differ across maturation given the adult growth spurt. The aim of this study is to quantify the magnitude of asymmetry in a number of kinetic variables ...