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Updated: Aug 29, 2026
Rating L-DOPA-Induced Dyskinesias in the Unilaterally 6-OHDA-Lesioned Rat Model of Parkinson's Disease
Published on: October 4, 2021
Embryonic mesencephalic grafts increase levodopa-induced forelimb hyperkinesia in parkinsonian rats
Kathy Steece-Collier1, Timothy J Collier, Paul D Danielson
1Department of Neurological Science, Research Center for Brain Repair, Rush Presbyterian St Luke's Medical Center, Chicago, Illinois 60612, USA. kathy_a_steece-collier@rush.edu
Abstract:
Recent observations from clinical trials of neural grafting for Parkinson's disease (PD) have demonstrated that grafted dopamine neurons can worsen dyskinesias in some graft recipients. This deleterious side effect reveals a new challenge for neural transplantation, that of elucidating mechanisms underlying these postgraft dyskinesias. One problem facing this challenge is the availability of a cost-effective and reliable animal model in which to pursue initial investigations. In the current study, we investigated the interaction of an embryonic ventral mesencephalic (VM) dopamine (DA) neuron graft on levodopa (LD)-induced dyskinetic movements in unilaterally 6-hydroxydopamine-lesioned rats. Rats were administered LD (levodopa-carbidopa, 50:5 mg/kg) twice daily for 6 weeks after either a sham graft or VM DA graft. Although a single solid graft of embryonic DA neurons can prevent progression of some lesioned-induced behavioral abnormalities such as LD-induced rotation and dystonia, it significantly increases hyperkinetic movements of the contralateral forelimb. This differential effect of grafted neurons on abnormal behavioral profiles is reminiscent of that reported in grafted patients with PD. Data from this study illustrate important similarities between this model of parkinsonism and PD in human patients that make it suitable for initial preclinical investigations into possible mechanisms underlying postgraft aggravation of dyskinetic movements.
Insights
Neural grafts for Parkinson's disease (PD) can worsen dyskinesias. This study shows that embryonic dopamine neuron grafts in rats increase hyperkinetic movements, highlighting a new challenge for neural transplantation therapies.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Pharmacology
Background:
- Clinical trials of neural grafting for Parkinson's disease (PD) indicate grafted dopamine neurons can exacerbate dyskinesias.
- Understanding the mechanisms behind post-transplant dyskinesias is crucial for advancing neural transplantation therapies.
Purpose of the Study:
- To investigate the effects of embryonic ventral mesencephalic (VM) dopamine neuron grafts on levodopa (LD)-induced dyskinetic movements in a rat model of PD.
- To evaluate the utility of this animal model for preclinical research into post-transplant dyskinesias.
Main Methods:
- Unilaterally 6-hydroxydopamine-lesioned rats received either a sham graft or a VM dopamine neuron graft.
- Following grafting, rats were administered levodopa-carbidopa (LD) twice daily for six weeks.
- Behavioral abnormalities, including rotation, dystonia, and hyperkinetic movements, were assessed.
Main Results:
- While VM dopamine neuron grafts mitigated some LD-induced motor deficits like rotation and dystonia, they significantly increased hyperkinetic movements in the contralateral forelimb.
- This differential effect on behavioral profiles mirrors observations in human PD patients who have received neural grafts.
Conclusions:
- The rat model with VM dopamine neuron grafts exhibits key similarities to human PD patients experiencing post-transplant dyskinesias.
- This model provides a valuable platform for preclinical investigation into the mechanisms underlying aggravated dyskinetic movements after neural transplantation in Parkinson's disease.
