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Embryonic mesencephalic grafts increase levodopa-induced forelimb hyperkinesia in parkinsonian rats.
Mov Disord. 2003 Dec; 18(12):1442-54.MD

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.

Authors+Show Affiliations

Department of Neurological Science, Research Center for Brain Repair, Rush Presbyterian St Luke's Medical Center, Chicago, Illinois 60612, USA. kathy_a_steece-collier@rush.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

14673880

Citation

Steece-Collier, Kathy, et al. "Embryonic Mesencephalic Grafts Increase Levodopa-induced Forelimb Hyperkinesia in Parkinsonian Rats." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 18, no. 12, 2003, pp. 1442-54.
Steece-Collier K, Collier TJ, Danielson PD, et al. Embryonic mesencephalic grafts increase levodopa-induced forelimb hyperkinesia in parkinsonian rats. Mov Disord. 2003;18(12):1442-54.
Steece-Collier, K., Collier, T. J., Danielson, P. D., Kurlan, R., Yurek, D. M., & Sladek, J. R. (2003). Embryonic mesencephalic grafts increase levodopa-induced forelimb hyperkinesia in parkinsonian rats. Movement Disorders : Official Journal of the Movement Disorder Society, 18(12), 1442-54.
Steece-Collier K, et al. Embryonic Mesencephalic Grafts Increase Levodopa-induced Forelimb Hyperkinesia in Parkinsonian Rats. Mov Disord. 2003;18(12):1442-54. PubMed PMID: 14673880.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Embryonic mesencephalic grafts increase levodopa-induced forelimb hyperkinesia in parkinsonian rats. AU - Steece-Collier,Kathy, AU - Collier,Timothy J, AU - Danielson,Paul D, AU - Kurlan,Roger, AU - Yurek,David M, AU - Sladek,John R,Jr PY - 2003/12/16/pubmed PY - 2004/4/29/medline PY - 2003/12/16/entrez SP - 1442 EP - 54 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov Disord VL - 18 IS - 12 N2 - 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. SN - 0885-3185 UR - https://www.unboundmedicine.com/medline/citation/14673880/Embryonic_mesencephalic_grafts_increase_levodopa_induced_forelimb_hyperkinesia_in_parkinsonian_rats_ L2 - https://doi.org/10.1002/mds.10588 DB - PRIME DP - Unbound Medicine ER -