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Neuroinflammation in the generation of post-transplantation dyskinesia in Parkinson's disease.
Neurobiol Dis. 2008 Nov; 32(2):220-8.ND

Abstract

The observation that neural grafts can induce dyskinesias has severely hindered the development of a transplantation therapy for Parkinson's disease (PD). We addressed the hypothesis that inflammatory responses within and around an intrastriatal graft containing dopamine neurons can trigger dyskinetic behaviors. We subjected rats to unilateral nigrostriatal lesions with 6-hydroxydopamine (6-OHDA) and treated them with L-DOPA for 21 days in order to induce abnormal involuntary movements (AIMs). Subsequently, we grafted the rats with allogeneic embryonic ventral mesencephalic tissue in the dopamine-denervated striatum. In agreement with earlier studies, the grafted rats developed dyskinesia-like AIMs in response to amphetamine. We then used two experimental approaches to induce an inflammatory response and examined if the amphetamine-induced AIMs worsened or if spontaneous AIMs developed. In one experiment, we challenged the neural graft hosts immunologically with an orthotopic skin allograft of the same genetic origin as the intracerebral neural allograft. In another experiment, we infused the pro-inflammatory cytokine interleukin 2 (IL-2) adjacent to the intrastriatal grafts using osmotic minipumps. The skin allograft induced rapid rejection of the mesencephalic allografts, leading to disappearance of the amphetamine-induced AIMs. Contrary to our hypothesis, the rejection process itself did not elicit AIMs. Likewise, the IL-2 infusion did not induce spontaneous AIMs, nor did it alter L-DOPA-induced AIMs. The IL-2 infusions did, however, elicit the predicted marked striatal inflammation, as evidenced by the presence of activated microglia and IL2Ralpha-positive cells. These results indicate that an inflammatory response in and around grafted dopaminergic neurons is not sufficient to evoke dyskinetic behaviors in experimental models of PD.

Authors+Show Affiliations

Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Sweden. laneel@Cardiff.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18675359

Citation

Lane, E L., et al. "Neuroinflammation in the Generation of Post-transplantation Dyskinesia in Parkinson's Disease." Neurobiology of Disease, vol. 32, no. 2, 2008, pp. 220-8.
Lane EL, Soulet D, Vercammen L, et al. Neuroinflammation in the generation of post-transplantation dyskinesia in Parkinson's disease. Neurobiol Dis. 2008;32(2):220-8.
Lane, E. L., Soulet, D., Vercammen, L., Cenci, M. A., & Brundin, P. (2008). Neuroinflammation in the generation of post-transplantation dyskinesia in Parkinson's disease. Neurobiology of Disease, 32(2), 220-8. https://doi.org/10.1016/j.nbd.2008.06.011
Lane EL, et al. Neuroinflammation in the Generation of Post-transplantation Dyskinesia in Parkinson's Disease. Neurobiol Dis. 2008;32(2):220-8. PubMed PMID: 18675359.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroinflammation in the generation of post-transplantation dyskinesia in Parkinson's disease. AU - Lane,E L, AU - Soulet,D, AU - Vercammen,L, AU - Cenci,M A, AU - Brundin,P, Y1 - 2008/07/03/ PY - 2008/04/30/received PY - 2008/06/17/revised PY - 2008/06/18/accepted PY - 2008/8/5/pubmed PY - 2009/4/9/medline PY - 2008/8/5/entrez SP - 220 EP - 8 JF - Neurobiology of disease JO - Neurobiol Dis VL - 32 IS - 2 N2 - The observation that neural grafts can induce dyskinesias has severely hindered the development of a transplantation therapy for Parkinson's disease (PD). We addressed the hypothesis that inflammatory responses within and around an intrastriatal graft containing dopamine neurons can trigger dyskinetic behaviors. We subjected rats to unilateral nigrostriatal lesions with 6-hydroxydopamine (6-OHDA) and treated them with L-DOPA for 21 days in order to induce abnormal involuntary movements (AIMs). Subsequently, we grafted the rats with allogeneic embryonic ventral mesencephalic tissue in the dopamine-denervated striatum. In agreement with earlier studies, the grafted rats developed dyskinesia-like AIMs in response to amphetamine. We then used two experimental approaches to induce an inflammatory response and examined if the amphetamine-induced AIMs worsened or if spontaneous AIMs developed. In one experiment, we challenged the neural graft hosts immunologically with an orthotopic skin allograft of the same genetic origin as the intracerebral neural allograft. In another experiment, we infused the pro-inflammatory cytokine interleukin 2 (IL-2) adjacent to the intrastriatal grafts using osmotic minipumps. The skin allograft induced rapid rejection of the mesencephalic allografts, leading to disappearance of the amphetamine-induced AIMs. Contrary to our hypothesis, the rejection process itself did not elicit AIMs. Likewise, the IL-2 infusion did not induce spontaneous AIMs, nor did it alter L-DOPA-induced AIMs. The IL-2 infusions did, however, elicit the predicted marked striatal inflammation, as evidenced by the presence of activated microglia and IL2Ralpha-positive cells. These results indicate that an inflammatory response in and around grafted dopaminergic neurons is not sufficient to evoke dyskinetic behaviors in experimental models of PD. SN - 1095-953X UR - https://www.unboundmedicine.com/medline/citation/18675359/Neuroinflammation_in_the_generation_of_post_transplantation_dyskinesia_in_Parkinson's_disease_ DB - PRIME DP - Unbound Medicine ER -