title: Amelioration of non-motor dysfunctions after transplantation of human dopamine neurons in a model of Parkinson's disease.
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.
  
  
  OBJECTIVE
  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.
authors: Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales CF10 3AX, UK. Electronic address: lelosmj@cf.ac.uk.
authors: M J
authors: MJ
authors: Lelos
authors: Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales CF10 3AX, UK.
authors: R J
authors: RJ
authors: Morgan
authors: Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales CF10 3AX, UK.
authors: C M
authors: CM
authors: Kelly
authors: Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales CF10 3AX, UK.
authors: E M
authors: EM
authors: Torres
authors: Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales CF10 3AX, UK.
authors: A E
authors: AE
authors: Rosser
authors: Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales CF10 3AX, UK.
authors: S B
authors: SB
authors: Dunnett
mesh_terms: D000818:Animals; D064026:Calbindins / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology / Q000601:surgery*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000502:physiology / Q000637:transplantation*; D005260:Female; D005333:Fetus / Q000166:cytology; D007839:Functional Laterality / Q000187:drug effects; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism; D006801:Humans; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000293:injuries; D009068:Movement / Q000502:physiology; D009498:Neurotoxins / Q000633:toxicity; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000150:complications* / Q000209:etiology / Q000601:surgery*; D010468:Perceptual Disorders / Q000209:etiology / Q000601:surgery*; D051381:Rats; D011930:Reaction Time; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014796:Visual Perception / Q000502:physiology
chemical_list: D064026:Calbindins; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D009498:Neurotoxins; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase
keywords: Cell transplantation; Dopamine; Non-motor symptoms; Parkinson's disease; Ventral mesencephalon; Visuo–spatial tasks