Neuroinflammation in the generation of post-transplantation dyskinesia in Parkinson's disease.
Lane, Emma LU ; Soulet, Denis LU ; Vercammen, L ; Cenci Nilsson, Angela LU
and Brundin, Patrik
LU
(2008)
In Neurobiology of Disease
32.
p.220-228
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1223534
- author
- Lane, Emma
LU
; Soulet, Denis
LU
; Vercammen, L
; Cenci Nilsson, Angela
LU
and Brundin, Patrik
LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Neurobiology of Disease
- volume
- 32
- pages
- 220 - 228
- publisher
- Elsevier
- external identifiers
-
- wos:000260549100004
- pmid:18675359
- scopus:53749099718
- pmid:18675359
- ISSN
- 0969-9961
- DOI
- 10.1016/j.nbd.2008.06.011
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neuronal Survival (013212041), Basal Ganglia (013212026)
- id
- a0191bb2-abaf-4c00-84c8-dc915feb8085 (old id 1223534)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/18675359?dopt=Abstract
- date added to LUP
- 2016-04-04 08:23:37
- date last changed
- 2022-01-29 03:26:42
@article{a0191bb2-abaf-4c00-84c8-dc915feb8085,
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.}},
author = {{Lane, Emma and Soulet, Denis and Vercammen, L and Cenci Nilsson, Angela and Brundin, Patrik}},
issn = {{0969-9961}},
language = {{eng}},
pages = {{220--228}},
publisher = {{Elsevier}},
series = {{Neurobiology of Disease}},
title = {{Neuroinflammation in the generation of post-transplantation dyskinesia in Parkinson's disease.}},
url = {{http://dx.doi.org/10.1016/j.nbd.2008.06.011}},
doi = {{10.1016/j.nbd.2008.06.011}},
volume = {{32}},
year = {{2008}},
}